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1.  Anatomy of the Epidemiological Literature on the 2003 SARS Outbreaks in Hong Kong and Toronto: A Time-Stratified Review 
PLoS Medicine  2010;7(5):e1000272.
Weijia Xing and colleagues reviewed the published epidemiological literature on SARS and show that less than a quarter of papers were published during the epidemic itself, suggesting that the research published lagged substantially behind the need for it.
Background
Outbreaks of emerging infectious diseases, especially those of a global nature, require rapid epidemiological analysis and information dissemination. The final products of those activities usually comprise internal memoranda and briefs within public health authorities and original research published in peer-reviewed journals. Using the 2003 severe acute respiratory syndrome (SARS) epidemic as an example, we conducted a comprehensive time-stratified review of the published literature to describe the different types of epidemiological outputs.
Methods and Findings
We identified and analyzed all published articles on the epidemiology of the SARS outbreak in Hong Kong or Toronto. The analysis was stratified by study design, research domain, data collection, and analytical technique. We compared the SARS-case and matched-control non-SARS articles published according to the timeline of submission, acceptance, and publication. The impact factors of the publishing journals were examined according to the time of publication of SARS articles, and the numbers of citations received by SARS-case and matched-control articles submitted during and after the epidemic were compared. Descriptive, analytical, theoretical, and experimental epidemiology concerned, respectively, 54%, 30%, 11%, and 6% of the studies. Only 22% of the studies were submitted, 8% accepted, and 7% published during the epidemic. The submission-to-acceptance and acceptance-to-publication intervals of the SARS articles submitted during the epidemic period were significantly shorter than the corresponding intervals of matched-control non-SARS articles published in the same journal issues (p<0.001 and p<0.01, respectively). The differences of median submission-to-acceptance intervals and median acceptance-to-publication intervals between SARS articles and their corresponding control articles were 106.5 d (95% confidence interval [CI] 55.0–140.1) and 63.5 d (95% CI 18.0–94.1), respectively. The median numbers of citations of the SARS articles submitted during the epidemic and over the 2 y thereafter were 17 (interquartile range [IQR] 8.0–52.0) and 8 (IQR 3.2–21.8), respectively, significantly higher than the median numbers of control article citations (15, IQR 8.5–16.5, p<0.05, and 7, IQR 3.0–12.0, p<0.01, respectively).
Conclusions
A majority of the epidemiological articles on SARS were submitted after the epidemic had ended, although the corresponding studies had relevance to public health authorities during the epidemic. To minimize the lag between research and the exigency of public health practice in the future, researchers should consider adopting common, predefined protocols and ready-to-use instruments to improve timeliness, and thus, relevance, in addition to standardizing comparability across studies. To facilitate information dissemination, journal managers should reengineer their fast-track channels, which should be adapted to the purpose of an emerging outbreak, taking into account the requirement of high standards of quality for scientific journals and competition with other online resources.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every now and then, a new infectious disease appears in a human population or an old disease becomes much more common or more geographically widespread. Recently, several such “emerging infectious diseases” have become major public health problems. For example, HIV/AIDS, hepatitis C, and severe acute respiratory syndrome (SARS) have all emerged in the past three decades and spread rapidly round the world. When an outbreak (epidemic) of an emerging infectious disease occurs, epidemiologists (scientists who study the causes, distribution, and control of diseases in populations) swing into action, collecting and analyzing data on the new threat to human health. Epidemiological studies are rapidly launched to identify the causative agent of the new disease, to investigate how the disease spreads, to define diagnostic criteria for the disease, to evaluate potential treatments, and to devise ways to control the disease's spread. Public health officials then use the results of these studies to bring the epidemic under control.
Why Was This Study Done?
Clearly, epidemics of emerging infectious diseases can only be controlled rapidly and effectively if the results of epidemiological studies are made widely available in a timely manner. Public health bulletins (for example, the Morbidity and Mortality Weekly Report from the US Centers from Disease Control and Prevention) are an important way of disseminating information as is the publication of original research in peer-reviewed academic journals. But how timely is this second dissemination route? Submission, peer-review, revision, re-review, acceptance, and publication of a piece of academic research can be a long process, the speed of which is affected by the responses of both authors and journals. In this study, the researchers analyze how the results of academic epidemiological research are submitted and published in journals during and after an emerging infectious disease epidemic using the 2003 SARS epidemic as an example. The first case of SARS was identified in Asia in February 2003 and rapidly spread around the world. 8,098 people became ill with SARS and 774 died before the epidemic was halted in July 2003.
What Did the Researchers Do and Find?
The researchers identified more than 300 journal articles covering epidemiological research into the SARS outbreak in Hong Kong, China, and Toronto, Canada (two cities strongly affected by the epidemic) that were published online or in print between January 1, 2003 and July 31, 2007. The researchers' analysis of these articles shows that more than half them were descriptive epidemiological studies, investigations that focused on describing the distribution of SARS; a third were analytical epidemiological studies that tried to discover the cause of SARS. Overall, 22% of the journal articles were submitted for publication during the epidemic. Only 8% of the articles were accepted for publication and only 7% were actually published during the epidemic. The median (average) submission-to-acceptance and acceptance-to-publication intervals for SARS articles submitted during the epidemic were 55 and 77.5 days, respectively, much shorter intervals than those for non-SARS articles published in the same journal issues. After the epidemic was over, the submission-to-acceptance and acceptance-to-publication intervals for SARS articles was similar to that of non-SARS articles.
What Do These Findings Mean?
These findings show that, although the academic response to the SARS epidemic was rapid, most articles on the epidemiology of SARS were published after the epidemic was over even though SARS was a major threat to public health. Possible reasons for this publication delay include the time taken by authors to prepare and undertake their studies, to write and submit their papers, and, possibly, their tendency to first submit their results to high profile journals. The time then taken by journals to review the studies, make decisions about publication, and complete the publication process might also have delayed matters. To minimize future delays in the publication of epidemiological research on emerging infectious diseases, epidemiologists could adopt common, predefined protocols and ready-to-use instruments, which would improve timeliness and ensure comparability across studies, suggest the researchers. Journals, in turn, could improve their fast-track procedures and could consider setting up online sections that could be activated when an emerging infectious disease outbreak occurred. Finally, journals could consider altering their review system to speed up the publication process provided the quality of the final published articles was not compromised.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000272.
The US National Institute of Allergy and Infectious Diseases provides information on emerging infectious diseases
The US Centers for Control and Prevention of Diseases also provides information about emerging infectious diseases, including links to other resources, and information on SARS
Wikipedia has a page on epidemiology (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The World Health Organization has information on SARS (in several languages)
doi:10.1371/journal.pmed.1000272
PMCID: PMC2864302  PMID: 20454570
2.  A study of institutional spending on open access publication fees in Germany 
PeerJ  2016;4:e2323.
Publication fees as a revenue source for open access publishing hold a prominent place on the agendas of researchers, policy makers, and academic publishers. This study contributes to the evolving empirical basis for funding these charges and examines how much German universities and research organisations spent on open access publication fees. Using self-reported cost data from the Open APC initiative, the analysis focused on the amount that was being spent on publication fees, and compared these expenditure with data from related Austrian (FWF) and UK (Wellcome Trust, Jisc) initiatives, in terms of both size and the proportion of articles being published in fully and hybrid open access journals. We also investigated how thoroughly self-reported articles were indexed in Crossref, a DOI minting agency for scholarly literature, and analysed how the institutional spending was distributed across publishers and journal titles. According to self-reported data from 30 German universities and research organisations between 2005 and 2015, expenditures on open access publication fees increased over the years in Germany and amounted to € 9,627,537 for 7,417 open access journal articles. The average payment was € 1,298, and the median was € 1,231. A total of 94% of the total article volume included in the study was supported in accordance with the price cap of € 2,000, a limit imposed by the Deutsche Forschungsgemeinschaft (DFG) as part of its funding activities for open access funding at German universities. Expenditures varied considerably at the institutional level. There were also differences in how much the institutions spent per journal and publisher. These differences reflect, at least in part, the varying pricing schemes in place including discounted publication fees. With an indexing coverage of 99%, Crossref thoroughly indexed the open access journals articles included in the study. A comparison with the related openly available cost data from Austria and the UK revealed that German universities and research organisations primarily funded articles in fully open access journals. By contrast, articles in hybrid journal accounted for the largest share of spending according to the Austrian and UK data. Fees paid for hybrid journals were on average more expensive than those paid for fully open access journals.
doi:10.7717/peerj.2323
PMCID: PMC4991862  PMID: 27602289
Open access; Open access journal; Article processing charges; Science policy; Scholarly publishing; Publication fees
3.  Conflict of Interest Reporting by Authors Involved in Promotion of Off-Label Drug Use: An Analysis of Journal Disclosures 
PLoS Medicine  2012;9(8):e1001280.
Aaron Kesselheim and colleagues investigate conflict of interest disclosures in articles authored by physicians and scientists identified in whistleblower complaints alleging illegal off-label marketing by pharmaceutical companies.
Background
Litigation documents reveal that pharmaceutical companies have paid physicians to promote off-label uses of their products through a number of different avenues. It is unknown whether physicians and scientists who have such conflicts of interest adequately disclose such relationships in the scientific publications they author.
Methods and Findings
We collected whistleblower complaints alleging illegal off-label marketing from the US Department of Justice and other publicly available sources (date range: 1996–2010). We identified physicians and scientists described in the complaints as having financial relationships with defendant manufacturers, then searched Medline for articles they authored in the subsequent three years. We assessed disclosures made in articles related to the off-label use in question, determined the frequency of adequate disclosure statements, and analyzed characteristics of the authors (specialty, author position) and articles (type, connection to off-label use, journal impact factor, citation count/year). We identified 39 conflicted individuals in whistleblower complaints. They published 404 articles related to the drugs at issue in the whistleblower complaints, only 62 (15%) of which contained an adequate disclosure statement. Most articles had no disclosure (43%) or did not mention the pharmaceutical company (40%). Adequate disclosure rates varied significantly by article type, with commentaries less likely to have adequate disclosure compared to articles reporting original studies or trials (adjusted odds ratio [OR] = 0.10, 95%CI = 0.02–0.67, p = 0.02). Over half of the authors (22/39, 56%) made no adequate disclosures in their articles. However, four of six authors with ≥25 articles disclosed in about one-third of articles (range: 10/36–8/25 [28%–32%]).
Conclusions
One in seven authors identified in whistleblower complaints as involved in off-label marketing activities adequately disclosed their conflict of interest in subsequent journal publications. This is a much lower rate of adequate disclosure than has been identified in previous studies. The non-disclosure patterns suggest shortcomings with authors and the rigor of journal practices.
Please see later in the article for the Editors' Summary
Editor's Summary
Background
Off-label use of pharmaceuticals is the practice of prescribing a drug for a condition or age group, or in a dose or form of administration, that has not been specifically approved by a formal regulatory body, such as the US Food and Drug Administration (FDA). Off-label prescribing is common all over the world. In the US, although it is legal for doctors to prescribe drugs off-label and discuss such clinical uses with colleagues, it is illegal for pharmaceutical companies to directly promote off-label uses of any of their products. Revenue from off-label uses can be lucrative for drug companies and even surpass the income from approved uses. Therefore, many pharmaceutical companies have paid physicians and scientists to promote off-label use of their products as part of their marketing programs.
Why Was This Study Done?
Recently, a number of pharmaceutical companies have been investigated in the US for illegal marketing programs that promote off-label uses of their products and have had to pay billions of dollars in court settlements. As part of these investigations, doctors and scientists were identified who were paid by the companies to deliver lectures and conduct other activities to support off-label uses. When the same physicians and scientists also wrote articles about these drugs for medical journals, their financial relationships would have constituted clear conflicts of interest that should have been declared alongside the journal articles. So, in this study, the researchers identified such authors, examined their publications, and assessed the adequacy of conflict of interest disclosures made in these publications.
What Did the Researchers Do and Find?
The researchers used disclosed information from the US Department of Justice, media reports, and data from a non-governmental organization that tracks federal fraud actions, to find whistleblower complaints alleging illegal off-label promotion. Then they identified the doctors and scientists described in the complaints as having financial relationships with the defendant drug companies and searched Medline for articles authored by these experts in the subsequent three years. Using a four step approach, the researchers assessed the adequacy of conflict of interest disclosures made in articles relating to the off-label uses in question.
Using these methods, the researchers examined 26 complaints alleging illegal off-label promotion and identified the 91 doctors and scientists recorded as being involved in this practice. The researchers found 39 (43%) of these 91 experts had authored 404 related publications. In the complaints, these 39 experts were alleged to have engaged in 42 relationships with the relevant drug company: the most common activity was acting as a paid speaker (n = 26, 62%) but also writing reviews or articles on behalf of the company (n = 7), acting as consultants or advisory board members (n = 3), and receiving gifts/honoraria (n = 3), research support funds (n = 2), and educational support funds (n = 1). However, the researchers found that only 62 (15%) of the 404 related articles had adequate disclosures—43% (148) had no disclosure at all, 4% had statements denying any conflicts of interest, 40% had disclosures that did not mention the drug manufacturer, and 13% had disclosures that mentioned the manufacturer but inadequately conveyed the nature of the relationship between author and drug manufacturer reported in the complaint. The researchers also found that adequate disclosure rates varied significantly by article type, with commentaries significantly less likely to have adequate disclosure compared to articles reporting studies or trials.
What Do These Findings Mean?
These findings show the substantial deficiencies in the adequacy of conflict-of-interest disclosures made by authors who had been paid by pharmaceutical manufacturers as part of off-label marketing activities: only one in seven authors fully disclosed their conflict of interest in their published articles. This low figure is troubling and suggests that approaches to controlling the effects of conflicts of interest that rely on author candidness are inadequate and furthermore, journal practices are not robust enough and need to be improved. In the meantime, readers have no option but to interpret conflict of interest disclosures, particularly in relation to off-label uses, with caution.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001280.
The US FDA provides a guide on the use of off-label drugs
The US Agency for Healthcare Research and Quality offers a patient guide to off-label drugs
ProPublica offers a web-based tool to identify physicians who have financial relationships with certain pharmaceutical companies
Wikipedia has a good description of off-label drug use (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The Institute for Medicine as a Profession maintains a list of policies regulating physicians' financial relationships that are in place at US-based academic medical centers
doi:10.1371/journal.pmed.1001280
PMCID: PMC3413710  PMID: 22899894
4.  Quantity, topics, methods and findings of randomised controlled trials published by German university departments of general practice – systematic review 
Trials  2016;17:211.
Background
Academic infrastructures and networks for clinical research in primary care receive little funding in Germany. We aimed to provide an overview of the quantity, topics, methods and findings of randomised controlled trials published by German university departments of general practice.
Methods
We searched Scopus (last search done in April 2015), publication lists of institutes and references of included articles. We included randomised trials published between January 2000 and December 2014 with a first or last author affiliated with a German university department of general practice or family medicine. Risk of bias was assessed with the Cochrane tool, and study findings were quantified using standardised mean differences (SMDs).
Results
Thirty-three trials met the inclusion criteria. Seventeen were cluster-randomised trials, with a majority investigating interventions aimed at improving processes compared with usual care. Sample sizes varied between 6 and 606 clusters and 168 and 7807 participants. The most frequent methodological problem was risk of selection bias due to recruitment of individuals after randomisation of clusters. Effects of interventions over usual care were mostly small (SMD <0.3). Sixteen trials randomising individual participants addressed a variety of treatment and educational interventions. Sample sizes varied between 20 and 1620 participants. The methodological quality of the trials was highly variable. Again, effects of experimental interventions over controls were mostly small.
Conclusions
Despite limited funding, German university institutes of general practice or family medicine are increasingly performing randomised trials. Cluster-randomised trials on practice improvement are a focus, but problems with allocation concealment are frequent.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1328-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s13063-016-1328-y
PMCID: PMC4842270  PMID: 27107809
Germany; Primary care; General practice; Randomised controlled trials; Academic performance
5.  Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials 
PLoS Medicine  2016;13(6):e1002046.
Background
Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees.
Methods and Findings
We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner’s right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements.
Conclusions
Publication agreements constraining academic authors’ independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol.
In a document analysis of trial protocols and publications, Erik von Elm and colleagues investigate the potential impact of publication agreements between industry sponsors and academic investigators.
Author Summary
Why Was This Study Done?
Many randomized trials are designed and sponsored by for-profit companies that contract academic investigators to recruit and manage patients.
Clinical research under these circumstances is a business transaction that bears the potential for conflicts of interest, in particular with respect to trial publication.
Besides evidence from a small sample, it was unclear how often trial protocols included publication agreements between industry and academic investigators, whether these agreements constrained the investigators’ publication rights, and how consistent such agreements stated in trial protocols were with those reported in corresponding publications.
What Did the Researchers Do and Find?
We investigated publication agreements in 647 randomized trial protocols approved in 2000–2003 by six research ethics committees in Switzerland, Canada, and Germany, and in 388 corresponding journal publications.
Seventy percent of protocols mentioned an agreement on publication rights between industry and academic investigators; in 86% of those agreements, industry retained the right to disapprove or at least review manuscripts before publication.
Seventy-four percent of agreements documented in protocols were not mentioned in corresponding journal articles.
What Do These Findings Mean?
Publication agreements constraining academic investigators’ independence are incompletely reported in publications; this may compromise the scientific evidence base established by randomized clinical trials.
More transparency on publication constraints is warranted.
Half of the included journal articles were published before 2008, leaving open the possibility that these findings do not reflect current reporting practice.
doi:10.1371/journal.pmed.1002046
PMCID: PMC4924795  PMID: 27352244
6.  Assessing Clinical and Life Sciences Performance of Research Institutions in Split, Croatia, 2000-2006 
Croatian medical journal  2008;49(2):164-174.
Aim
To evaluate publications of clinical and life scientists from research institutions in Split, Croatia, and the publication output from government-funded research projects of the University of Split School of Medicine.
Methods
We analyzed the number of publications from research institutions in Split, Croatia, in the 2000-2006 period, relative impact factors, predominant research fields, output of researchers from the University of Split School of Medicine receiving government research grants, and the average price of published article.
Results
From 2000 to 2006, clinical and life scientists published 350 articles indexed in Thomson Scientific database Current Contents. The number of articles increased from 30 in 2000 to 76 in 2006, and the average impact factor of journals where these articles were published increased from 2.03 in 2000 to 2.89 in 2006. Twenty percent of articles (72/350) were published in the Croatian Medical Journal. Principal investigators of the 12 research projects receiving government grants published 0 to 8 articles related to the project topic in the 2002-2006 research grant cycle. The research grantees published 78 original research articles, with an average price per article of € 29.210.
Conclusion
Although the number and impact factor of research articles published by clinical and life scientists from Split, Croatia, is increasing, it is still low when the number of scientists is taken into account. There should be better mechanisms of control and evaluation of research performance of government-funded research projects.
doi:10.3325/cmj.2008.2.164
PMCID: PMC2359877  PMID: 18461671
7.  Using Co-authorship Networks to Map and Analyse Global Neglected Tropical Disease Research with an Affiliation to Germany 
PLoS Neglected Tropical Diseases  2015;9(12):e0004182.
Background
Research on Neglected Tropical Diseases (NTDs) has increased in recent decades, and significant need-gaps in diagnostic and treatment tools remain. Analysing bibliometric data from published research is a powerful method for revealing research efforts, partnerships and expertise. We aim to identify and map NTD research networks in Germany and their partners abroad to enable an informed and transparent evaluation of German contributions to NTD research.
Methodology/Principal Findings
A SCOPUS database search for articles with German author affiliations that were published between 2002 and 2012 was conducted for kinetoplastid and helminth diseases. Open-access tools were used for data cleaning and scientometrics (OpenRefine), geocoding (OpenStreetMaps) and to create (Table2Net), visualise and analyse co-authorship networks (Gephi). From 26,833 publications from around the world that addressed 11 diseases, we identified 1,187 (4.4%) with at least one German author affiliation, and we processed 972 publications for the five most published-about diseases. Of those, we extracted 4,007 individual authors and 863 research institutions to construct co-author networks. The majority of co-authors outside Germany were from high-income countries and Brazil. Collaborations with partners on the African continent remain scattered. NTD research within Germany was distributed among 220 research institutions. We identified strong performers on an individual level by using classic parameters (number of publications, h-index) and social network analysis parameters (betweenness centrality). The research network characteristics varied strongly between diseases.
Conclusions/Significance
The share of NTD publications with German affiliations is approximately half of its share in other fields of medical research. This finding underlines the need to identify barriers and expand Germany’s otherwise strong research activities towards NTDs. A geospatial analysis of research collaborations with partners abroad can support decisions to strengthen research capacity, particularly in low- and middle-income countries, which were less involved in collaborations than high-income countries. Identifying knowledge hubs within individual researcher networks complements traditional scientometric indicators that are used to identify opportunities for collaboration. Using free tools to analyse research processes and output could facilitate data-driven health policies. Our findings contribute to the prioritisation of efforts in German NTD research at a time of impending local and global policy decisions.
Author Summary
Neglected tropical disease research has changed considerably in recent decades, and the German government is committed to addressing its past neglect of NTD research. Our aim was to use an innovative social network analysis of bibliometric data to map neglected tropical disease research networks that are inside of and affiliated with Germany, thereby enabling data-driven health policy decision-making. We created and analysed co-author networks from publications in the SCOPUS database, with a focus on five diseases. We found that Germany's share of global publication output for NTDs is approximately half that of other medical research fields. Furthermore, we identified institutions with prominent NTD research within Germany and strong research collaborations between German institutions and partners abroad, mostly in other high-income countries. This allowed an assessment of strong collaborations for further development, e.g., for research capacity strengthening in low-income-countries, but also for identifying missed opportunities for collaboration within the network. Through co-authorship network analysis of individual researcher networks, we identified strong performers by using classic bibliometric parameters, and we identified academic talent by social network analysis parameters on an individual level.
doi:10.1371/journal.pntd.0004182
PMCID: PMC4703140  PMID: 26719978
8.  An Update: NIH Research Funding for Palliative Medicine 2006 to 2010 
Journal of Palliative Medicine  2013;16(2):125-129.
Abstract
Background
Palliative care clinical and educational programs are expanding to meet the needs of seriously ill patients and their families. Multiple reports call for an enhanced palliative care evidence base.
Objective
To examine current National Institutes of Health (NIH) funding of palliative medicine research and changes since our 2008 report.1
Methods
We sought to identify NIH funding of palliative medicine from 2006 to 2010 in two stages. First, we searched the NIH grants database RePorter2 for grants with key words “palliative care,” “end-of-life care,” “hospice,” and “end of life.” Second, we identified palliative care researchers likely to have secured NIH funding using three strategies: (1) We abstracted the first and last authors' names from original investigations published in major palliative medicine journals from 2008 to 2010; (2) we abstracted these names from a PubMed generated list of all original articles published in major medicine, nursing, and subspecialty journals using the above key words Medical Subject Headings (MESH) terms “palliative care,” “end-of-life care,” “hospice,” and “end of life;” and (3) we identified editorial board members of palliative medicine journals and key members of palliative medicine research initiatives. We crossmatched the pooled names against NIH grants funded from 2006 to 2010.
Results
The NIH RePorter search yielded 653 grants and the author search identified an additional 352 grants. Compared to 2001 to 2005, 589 (240%) more grants were NIH funded. The 391 grants categorized as relevant to palliative medicine represented 294 unique PIs, an increase of 185 (269%) NIH funded palliative medicine researchers. The NIH supported 21% of the 1253 original palliative medicine research articles identified. Compared to 2001 to 2005, the percentage of grants funded by institutes other than the National Cancer Institute (NCI), the National Institute for Nursing Research (NINR), and the National Institute of Aging (NIA) increased from 15% to 20% of all grants.
Conclusions
When compared to 2001–2005, more palliative medicine investigators received NIH funding; and research funding has improved. Nevertheless, additional initiatives to further support palliative care research are needed.
doi:10.1089/jpm.2012.0427
PMCID: PMC3607902  PMID: 23336358
9.  Internet-Based Device-Assisted Remote Monitoring of Cardiovascular Implantable Electronic Devices 
Executive Summary
Objective
The objective of this Medical Advisory Secretariat (MAS) report was to conduct a systematic review of the available published evidence on the safety, effectiveness, and cost-effectiveness of Internet-based device-assisted remote monitoring systems (RMSs) for therapeutic cardiac implantable electronic devices (CIEDs) such as pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. The MAS evidence-based review was performed to support public financing decisions.
Clinical Need: Condition and Target Population
Sudden cardiac death (SCD) is a major cause of fatalities in developed countries. In the United States almost half a million people die of SCD annually, resulting in more deaths than stroke, lung cancer, breast cancer, and AIDS combined. In Canada each year more than 40,000 people die from a cardiovascular related cause; approximately half of these deaths are attributable to SCD.
Most cases of SCD occur in the general population typically in those without a known history of heart disease. Most SCDs are caused by cardiac arrhythmia, an abnormal heart rhythm caused by malfunctions of the heart’s electrical system. Up to half of patients with significant heart failure (HF) also have advanced conduction abnormalities.
Cardiac arrhythmias are managed by a variety of drugs, ablative procedures, and therapeutic CIEDs. The range of CIEDs includes pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. Bradycardia is the main indication for PMs and individuals at high risk for SCD are often treated by ICDs.
Heart failure (HF) is also a significant health problem and is the most frequent cause of hospitalization in those over 65 years of age. Patients with moderate to severe HF may also have cardiac arrhythmias, although the cause may be related more to heart pump or haemodynamic failure. The presence of HF, however, increases the risk of SCD five-fold, regardless of aetiology. Patients with HF who remain highly symptomatic despite optimal drug therapy are sometimes also treated with CRT devices.
With an increasing prevalence of age-related conditions such as chronic HF and the expanding indications for ICD therapy, the rate of ICD placement has been dramatically increasing. The appropriate indications for ICD placement, as well as the rate of ICD placement, are increasingly an issue. In the United States, after the introduction of expanded coverage of ICDs, a national ICD registry was created in 2005 to track these devices. A recent survey based on this national ICD registry reported that 22.5% (25,145) of patients had received a non-evidence based ICD and that these patients experienced significantly higher in-hospital mortality and post-procedural complications.
In addition to the increased ICD device placement and the upfront device costs, there is the need for lifelong follow-up or surveillance, placing a significant burden on patients and device clinics. In 2007, over 1.6 million CIEDs were implanted in Europe and the United States, which translates to over 5.5 million patient encounters per year if the recommended follow-up practices are considered. A safe and effective RMS could potentially improve the efficiency of long-term follow-up of patients and their CIEDs.
Technology
In addition to being therapeutic devices, CIEDs have extensive diagnostic abilities. All CIEDs can be interrogated and reprogrammed during an in-clinic visit using an inductive programming wand. Remote monitoring would allow patients to transmit information recorded in their devices from the comfort of their own homes. Currently most ICD devices also have the potential to be remotely monitored. Remote monitoring (RM) can be used to check system integrity, to alert on arrhythmic episodes, and to potentially replace in-clinic follow-ups and manage disease remotely. They do not currently have the capability of being reprogrammed remotely, although this feature is being tested in pilot settings.
Every RMS is specifically designed by a manufacturer for their cardiac implant devices. For Internet-based device-assisted RMSs, this customization includes details such as web application, multiplatform sensors, custom algorithms, programming information, and types and methods of alerting patients and/or physicians. The addition of peripherals for monitoring weight and pressure or communicating with patients through the onsite communicators also varies by manufacturer. Internet-based device-assisted RMSs for CIEDs are intended to function as a surveillance system rather than an emergency system.
Health care providers therefore need to learn each application, and as more than one application may be used at one site, multiple applications may need to be reviewed for alarms. All RMSs deliver system integrity alerting; however, some systems seem to be better geared to fast arrhythmic alerting, whereas other systems appear to be more intended for remote follow-up or supplemental remote disease management. The different RMSs may therefore have different impacts on workflow organization because of their varying frequency of interrogation and methods of alerts. The integration of these proprietary RM web-based registry systems with hospital-based electronic health record systems has so far not been commonly implemented.
Currently there are 2 general types of RMSs: those that transmit device diagnostic information automatically and without patient assistance to secure Internet-based registry systems, and those that require patient assistance to transmit information. Both systems employ the use of preprogrammed alerts that are either transmitted automatically or at regular scheduled intervals to patients and/or physicians.
The current web applications, programming, and registry systems differ greatly between the manufacturers of transmitting cardiac devices. In Canada there are currently 4 manufacturers—Medtronic Inc., Biotronik, Boston Scientific Corp., and St Jude Medical Inc.—which have regulatory approval for remote transmitting CIEDs. Remote monitoring systems are proprietary to the manufacturer of the implant device. An RMS for one device will not work with another device, and the RMS may not work with all versions of the manufacturer’s devices.
All Internet-based device-assisted RMSs have common components. The implanted device is equipped with a micro-antenna that communicates with a small external device (at bedside or wearable) commonly known as the transmitter. Transmitters are able to interrogate programmed parameters and diagnostic data stored in the patients’ implant device. The information transfer to the communicator can occur at preset time intervals with the participation of the patient (waving a wand over the device) or it can be sent automatically (wirelessly) without their participation. The encrypted data are then uploaded to an Internet-based database on a secure central server. The data processing facilities at the central database, depending on the clinical urgency, can trigger an alert for the physician(s) that can be sent via email, fax, text message, or phone. The details are also posted on the secure website for viewing by the physician (or their delegate) at their convenience.
Research Questions
The research directions and specific research questions for this evidence review were as follows:
To identify the Internet-based device-assisted RMSs available for follow-up of patients with therapeutic CIEDs such as PMs, ICDs, and CRT devices.
To identify the potential risks, operational issues, or organizational issues related to Internet-based device-assisted RM for CIEDs.
To evaluate the safety, acceptability, and effectiveness of Internet-based device-assisted RMSs for CIEDs such as PMs, ICDs, and CRT devices.
To evaluate the safety, effectiveness, and cost-effectiveness of Internet-based device-assisted RMSs for CIEDs compared to usual outpatient in-office monitoring strategies.
To evaluate the resource implications or budget impact of RMSs for CIEDs in Ontario, Canada.
Research Methods
Literature Search
The review included a systematic review of published scientific literature and consultations with experts and manufacturers of all 4 approved RMSs for CIEDs in Canada. Information on CIED cardiac implant clinics was also obtained from Provincial Programs, a division within the Ministry of Health and Long-Term Care with a mandate for cardiac implant specialty care. Various administrative databases and registries were used to outline the current clinical follow-up burden of CIEDs in Ontario. The provincial population-based ICD database developed and maintained by the Institute for Clinical Evaluative Sciences (ICES) was used to review the current follow-up practices with Ontario patients implanted with ICD devices.
Search Strategy
A literature search was performed on September 21, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from 1950 to September 2010. Search alerts were generated and reviewed for additional relevant literature until December 31, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search.
Inclusion Criteria
published between 1950 and September 2010;
English language full-reports and human studies;
original reports including clinical evaluations of Internet-based device-assisted RMSs for CIEDs in clinical settings;
reports including standardized measurements on outcome events such as technical success, safety, effectiveness, cost, measures of health care utilization, morbidity, mortality, quality of life or patient satisfaction;
randomized controlled trials (RCTs), systematic reviews and meta-analyses, cohort and controlled clinical studies.
Exclusion Criteria
non-systematic reviews, letters, comments and editorials;
reports not involving standardized outcome events;
clinical reports not involving Internet-based device assisted RM systems for CIEDs in clinical settings;
reports involving studies testing or validating algorithms without RM;
studies with small samples (<10 subjects).
Outcomes of Interest
The outcomes of interest included: technical outcomes, emergency department visits, complications, major adverse events, symptoms, hospital admissions, clinic visits (scheduled and/or unscheduled), survival, morbidity (disease progression, stroke, etc.), patient satisfaction, and quality of life.
Summary of Findings
The MAS evidence review was performed to review available evidence on Internet-based device-assisted RMSs for CIEDs published until September 2010. The search identified 6 systematic reviews, 7 randomized controlled trials, and 19 reports for 16 cohort studies—3 of these being registry-based and 4 being multi-centered. The evidence is summarized in the 3 sections that follow.
1. Effectiveness of Remote Monitoring Systems of CIEDs for Cardiac Arrhythmia and Device Functioning
In total, 15 reports on 13 cohort studies involving investigations with 4 different RMSs for CIEDs in cardiology implant clinic groups were identified in the review. The 4 RMSs were: Care Link Network® (Medtronic Inc,, Minneapolis, MN, USA); Home Monitoring® (Biotronic, Berlin, Germany); House Call 11® (St Jude Medical Inc., St Pauls, MN, USA); and a manufacturer-independent RMS. Eight of these reports were with the Home Monitoring® RMS (12,949 patients), 3 were with the Care Link® RMS (167 patients), 1 was with the House Call 11® RMS (124 patients), and 1 was with a manufacturer-independent RMS (44 patients). All of the studies, except for 2 in the United States, (1 with Home Monitoring® and 1 with House Call 11®), were performed in European countries.
The RMSs in the studies were evaluated with different cardiac implant device populations: ICDs only (6 studies), ICD and CRT devices (3 studies), PM and ICD and CRT devices (4 studies), and PMs only (2 studies). The patient populations were predominately male (range, 52%–87%) in all studies, with mean ages ranging from 58 to 76 years. One study population was unique in that RMSs were evaluated for ICDs implanted solely for primary prevention in young patients (mean age, 44 years) with Brugada syndrome, which carries an inherited increased genetic risk for sudden heart attack in young adults.
Most of the cohort studies reported on the feasibility of RMSs in clinical settings with limited follow-up. In the short follow-up periods of the studies, the majority of the events were related to detection of medical events rather than system configuration or device abnormalities. The results of the studies are summarized below:
The interrogation of devices on the web platform, both for continuous and scheduled transmissions, was significantly quicker with remote follow-up, both for nurses and physicians.
In a case-control study focusing on a Brugada population–based registry with patients followed-up remotely, there were significantly fewer outpatient visits and greater detection of inappropriate shocks. One death occurred in the control group not followed remotely and post-mortem analysis indicated early signs of lead failure prior to the event.
Two studies examined the role of RMSs in following ICD leads under regulatory advisory in a European clinical setting and noted:
– Fewer inappropriate shocks were administered in the RM group.
– Urgent in-office interrogations and surgical revisions were performed within 12 days of remote alerts.
– No signs of lead fracture were detected at in-office follow-up; all were detected at remote follow-up.
Only 1 study reported evaluating quality of life in patients followed up remotely at 3 and 6 months; no values were reported.
Patient satisfaction was evaluated in 5 cohort studies, all in short term follow-up: 1 for the Home Monitoring® RMS, 3 for the Care Link® RMS, and 1 for the House Call 11® RMS.
– Patients reported receiving a sense of security from the transmitter, a good relationship with nurses and physicians, positive implications for their health, and satisfaction with RM and organization of services.
– Although patients reported that the system was easy to implement and required less than 10 minutes to transmit information, a variable proportion of patients (range, 9% 39%) reported that they needed the assistance of a caregiver for their transmission.
– The majority of patients would recommend RM to other ICD patients.
– Patients with hearing or other physical or mental conditions hindering the use of the system were excluded from studies, but the frequency of this was not reported.
Physician satisfaction was evaluated in 3 studies, all with the Care Link® RMS:
– Physicians reported an ease of use and high satisfaction with a generally short-term use of the RMS.
– Physicians reported being able to address the problems in unscheduled patient transmissions or physician initiated transmissions remotely, and were able to handle the majority of the troubleshooting calls remotely.
– Both nurses and physicians reported a high level of satisfaction with the web registry system.
2. Effectiveness of Remote Monitoring Systems in Heart Failure Patients for Cardiac Arrhythmia and Heart Failure Episodes
Remote follow-up of HF patients implanted with ICD or CRT devices, generally managed in specialized HF clinics, was evaluated in 3 cohort studies: 1 involved the Home Monitoring® RMS and 2 involved the Care Link® RMS. In these RMSs, in addition to the standard diagnostic features, the cardiac devices continuously assess other variables such as patient activity, mean heart rate, and heart rate variability. Intra-thoracic impedance, a proxy measure for lung fluid overload, was also measured in the Care Link® studies. The overall diagnostic performance of these measures cannot be evaluated, as the information was not reported for patients who did not experience intra-thoracic impedance threshold crossings or did not undergo interventions. The trial results involved descriptive information on transmissions and alerts in patients experiencing high morbidity and hospitalization in the short study periods.
3. Comparative Effectiveness of Remote Monitoring Systems for CIEDs
Seven RCTs were identified evaluating RMSs for CIEDs: 2 were for PMs (1276 patients) and 5 were for ICD/CRT devices (3733 patients). Studies performed in the clinical setting in the United States involved both the Care Link® RMS and the Home Monitoring® RMS, whereas all studies performed in European countries involved only the Home Monitoring® RMS.
3A. Randomized Controlled Trials of Remote Monitoring Systems for Pacemakers
Two trials, both multicenter RCTs, were conducted in different countries with different RMSs and study objectives. The PREFER trial was a large trial (897 patients) performed in the United States examining the ability of Care Link®, an Internet-based remote PM interrogation system, to detect clinically actionable events (CAEs) sooner than the current in-office follow-up supplemented with transtelephonic monitoring transmissions, a limited form of remote device interrogation. The trial results are summarized below:
In the 375-day mean follow-up, 382 patients were identified with at least 1 CAE—111 patients in the control arm and 271 in the remote arm.
The event rate detected per patient for every type of CAE, except for loss of atrial capture, was higher in the remote arm than the control arm.
The median time to first detection of CAEs (4.9 vs. 6.3 months) was significantly shorter in the RMS group compared to the control group (P < 0.0001).
Additionally, only 2% (3/190) of the CAEs in the control arm were detected during a transtelephonic monitoring transmission (the rest were detected at in-office follow-ups), whereas 66% (446/676) of the CAEs were detected during remote interrogation.
The second study, the OEDIPE trial, was a smaller trial (379 patients) performed in France evaluating the ability of the Home Monitoring® RMS to shorten PM post-operative hospitalization while preserving the safety of conventional management of longer hospital stays.
Implementation and operationalization of the RMS was reported to be successful in 91% (346/379) of the patients and represented 8144 transmissions.
In the RM group 6.5% of patients failed to send messages (10 due to improper use of the transmitter, 2 with unmanageable stress). Of the 172 patients transmitting, 108 patients sent a total of 167 warnings during the trial, with a greater proportion of warnings being attributed to medical rather than technical causes.
Forty percent had no warning message transmission and among these, 6 patients experienced a major adverse event and 1 patient experienced a non-major adverse event. Of the 6 patients having a major adverse event, 5 contacted their physician.
The mean medical reaction time was faster in the RM group (6.5 ± 7.6 days vs. 11.4 ± 11.6 days).
The mean duration of hospitalization was significantly shorter (P < 0.001) for the RM group than the control group (3.2 ± 3.2 days vs. 4.8 ± 3.7 days).
Quality of life estimates by the SF-36 questionnaire were similar for the 2 groups at 1-month follow-up.
3B. Randomized Controlled Trials Evaluating Remote Monitoring Systems for ICD or CRT Devices
The 5 studies evaluating the impact of RMSs with ICD/CRT devices were conducted in the United States and in European countries and involved 2 RMSs—Care Link® and Home Monitoring ®. The objectives of the trials varied and 3 of the trials were smaller pilot investigations.
The first of the smaller studies (151 patients) evaluated patient satisfaction, achievement of patient outcomes, and the cost-effectiveness of the Care Link® RMS compared to quarterly in-office device interrogations with 1-year follow-up.
Individual outcomes such as hospitalizations, emergency department visits, and unscheduled clinic visits were not significantly different between the study groups.
Except for a significantly higher detection of atrial fibrillation in the RM group, data on ICD detection and therapy were similar in the study groups.
Health-related quality of life evaluated by the EuroQoL at 6-month or 12-month follow-up was not different between study groups.
Patients were more satisfied with their ICD care in the clinic follow-up group than in the remote follow-up group at 6-month follow-up, but were equally satisfied at 12- month follow-up.
The second small pilot trial (20 patients) examined the impact of RM follow-up with the House Call 11® system on work schedules and cost savings in patients randomized to 2 study arms varying in the degree of remote follow-up.
The total time including device interrogation, transmission time, data analysis, and physician time required was significantly shorter for the RM follow-up group.
The in-clinic waiting time was eliminated for patients in the RM follow-up group.
The physician talk time was significantly reduced in the RM follow-up group (P < 0.05).
The time for the actual device interrogation did not differ in the study groups.
The third small trial (115 patients) examined the impact of RM with the Home Monitoring® system compared to scheduled trimonthly in-clinic visits on the number of unplanned visits, total costs, health-related quality of life (SF-36), and overall mortality.
There was a 63.2% reduction in in-office visits in the RM group.
Hospitalizations or overall mortality (values not stated) were not significantly different between the study groups.
Patient-induced visits were higher in the RM group than the in-clinic follow-up group.
The TRUST Trial
The TRUST trial was a large multicenter RCT conducted at 102 centers in the United States involving the Home Monitoring® RMS for ICD devices for 1450 patients. The primary objectives of the trial were to determine if remote follow-up could be safely substituted for in-office clinic follow-up (3 in-office visits replaced) and still enable earlier physician detection of clinically actionable events.
Adherence to the protocol follow-up schedule was significantly higher in the RM group than the in-office follow-up group (93.5% vs. 88.7%, P < 0.001).
Actionability of trimonthly scheduled checks was low (6.6%) in both study groups. Overall, actionable causes were reprogramming (76.2%), medication changes (24.8%), and lead/system revisions (4%), and these were not different between the 2 study groups.
The overall mean number of in-clinic and hospital visits was significantly lower in the RM group than the in-office follow-up group (2.1 per patient-year vs. 3.8 per patient-year, P < 0.001), representing a 45% visit reduction at 12 months.
The median time from onset of first arrhythmia to physician evaluation was significantly shorter (P < 0.001) in the RM group than in the in-office follow-up group for all arrhythmias (1 day vs. 35.5 days).
The median time to detect clinically asymptomatic arrhythmia events—atrial fibrillation (AF), ventricular fibrillation (VF), ventricular tachycardia (VT), and supra-ventricular tachycardia (SVT)—was also significantly shorter (P < 0.001) in the RM group compared to the in-office follow-up group (1 day vs. 41.5 days) and was significantly quicker for each of the clinical arrhythmia events—AF (5.5 days vs. 40 days), VT (1 day vs. 28 days), VF (1 day vs. 36 days), and SVT (2 days vs. 39 days).
System-related problems occurred infrequently in both groups—in 1.5% of patients (14/908) in the RM group and in 0.7% of patients (3/432) in the in-office follow-up group.
The overall adverse event rate over 12 months was not significantly different between the 2 groups and individual adverse events were also not significantly different between the RM group and the in-office follow-up group: death (3.4% vs. 4.9%), stroke (0.3% vs. 1.2%), and surgical intervention (6.6% vs. 4.9%), respectively.
The 12-month cumulative survival was 96.4% (95% confidence interval [CI], 95.5%–97.6%) in the RM group and 94.2% (95% confidence interval [CI], 91.8%–96.6%) in the in-office follow-up group, and was not significantly different between the 2 groups (P = 0.174).
The CONNECT Trial
The CONNECT trial, another major multicenter RCT, involved the Care Link® RMS for ICD/CRT devices in a15-month follow-up study of 1,997 patients at 133 sites in the United States. The primary objective of the trial was to determine whether automatically transmitted physician alerts decreased the time from the occurrence of clinically relevant events to medical decisions. The trial results are summarized below:
Of the 575 clinical alerts sent in the study, 246 did not trigger an automatic physician alert. Transmission failures were related to technical issues such as the alert not being programmed or not being reset, and/or a variety of patient factors such as not being at home and the monitor not being plugged in or set up.
The overall mean time from the clinically relevant event to the clinical decision was significantly shorter (P < 0.001) by 17.4 days in the remote follow-up group (4.6 days for 172 patients) than the in-office follow-up group (22 days for 145 patients).
– The median time to a clinical decision was shorter in the remote follow-up group than in the in-office follow-up group for an AT/AF burden greater than or equal to 12 hours (3 days vs. 24 days) and a fast VF rate greater than or equal to 120 beats per minute (4 days vs. 23 days).
Although infrequent, similar low numbers of events involving low battery and VF detection/therapy turned off were noted in both groups. More alerts, however, were noted for out-of-range lead impedance in the RM group (18 vs. 6 patients), and the time to detect these critical events was significantly shorter in the RM group (same day vs. 17 days).
Total in-office clinic visits were reduced by 38% from 6.27 visits per patient-year in the in-office follow-up group to 3.29 visits per patient-year in the remote follow-up group.
Health care utilization visits (N = 6,227) that included cardiovascular-related hospitalization, emergency department visits, and unscheduled clinic visits were not significantly higher in the remote follow-up group.
The overall mean length of hospitalization was significantly shorter (P = 0.002) for those in the remote follow-up group (3.3 days vs. 4.0 days) and was shorter both for patients with ICD (3.0 days vs. 3.6 days) and CRT (3.8 days vs. 4.7 days) implants.
The mortality rate between the study arms was not significantly different between the follow-up groups for the ICDs (P = 0.31) or the CRT devices with defribillator (P = 0.46).
Conclusions
There is limited clinical trial information on the effectiveness of RMSs for PMs. However, for RMSs for ICD devices, multiple cohort studies and 2 large multicenter RCTs demonstrated feasibility and significant reductions in in-office clinic follow-ups with RMSs in the first year post implantation. The detection rates of clinically significant events (and asymptomatic events) were higher, and the time to a clinical decision for these events was significantly shorter, in the remote follow-up groups than in the in-office follow-up groups. The earlier detection of clinical events in the remote follow-up groups, however, was not associated with lower morbidity or mortality rates in the 1-year follow-up. The substitution of almost all the first year in-office clinic follow-ups with RM was also not associated with an increased health care utilization such as emergency department visits or hospitalizations.
The follow-up in the trials was generally short-term, up to 1 year, and was a more limited assessment of potential longer term device/lead integrity complications or issues. None of the studies compared the different RMSs, particularly the different RMSs involving patient-scheduled transmissions or automatic transmissions. Patients’ acceptance of and satisfaction with RM were reported to be high, but the impact of RM on patients’ health-related quality of life, particularly the psychological aspects, was not evaluated thoroughly. Patients who are not technologically competent, having hearing or other physical/mental impairments, were identified as potentially disadvantaged with remote surveillance. Cohort studies consistently identified subgroups of patients who preferred in-office follow-up. The evaluation of costs and workflow impact to the health care system were evaluated in European or American clinical settings, and only in a limited way.
Internet-based device-assisted RMSs involve a new approach to monitoring patients, their disease progression, and their CIEDs. Remote monitoring also has the potential to improve the current postmarket surveillance systems of evolving CIEDs and their ongoing hardware and software modifications. At this point, however, there is insufficient information to evaluate the overall impact to the health care system, although the time saving and convenience to patients and physicians associated with a substitution of in-office follow-up by RM is more certain. The broader issues surrounding infrastructure, impacts on existing clinical care systems, and regulatory concerns need to be considered for the implementation of Internet-based RMSs in jurisdictions involving different clinical practices.
PMCID: PMC3377571  PMID: 23074419
10.  Conflicts of Interest at Medical Journals: The Influence of Industry-Supported Randomised Trials on Journal Impact Factors and Revenue – Cohort Study 
PLoS Medicine  2010;7(10):e1000354.
Andreas Lundh and colleagues investigated the effect of publication of large industry-supported trials on citations and journal income, through reprint sales, in six general medical journals
Background
Transparency in reporting of conflict of interest is an increasingly important aspect of publication in medical journals. Publication of large industry-supported trials may generate many citations and journal income through reprint sales and thereby be a source of conflicts of interest for journals. We investigated industry-supported trials' influence on journal impact factors and revenue.
Methods and Findings
We sampled six major medical journals (Annals of Internal Medicine, Archives of Internal Medicine, BMJ, JAMA, The Lancet, and New England Journal of Medicine [NEJM]). For each journal, we identified randomised trials published in 1996–1997 and 2005–2006 using PubMed, and categorized the type of financial support. Using Web of Science, we investigated citations of industry-supported trials and the influence on journal impact factors over a ten-year period. We contacted journal editors and retrieved tax information on income from industry sources. The proportion of trials with sole industry support varied between journals, from 7% in BMJ to 32% in NEJM in 2005–2006. Industry-supported trials were more frequently cited than trials with other types of support, and omitting them from the impact factor calculation decreased journal impact factors. The decrease varied considerably between journals, with 1% for BMJ to 15% for NEJM in 2007. For the two journals disclosing data, income from the sales of reprints contributed to 3% and 41% of the total income for BMJ and The Lancet in 2005–2006.
Conclusions
Publication of industry-supported trials was associated with an increase in journal impact factors. Sales of reprints may provide a substantial income. We suggest that journals disclose financial information in the same way that they require them from their authors, so that readers can assess the potential effect of different types of papers on journals' revenue and impact.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Medical journals publish many different types of papers that inform doctors about the latest research advances and the latest treatments for their patients. They publish articles that describe laboratory-based research into the causes of diseases and the identification of potential new drugs. They publish the results of early clinical trials in which a few patients are given a potential new drug to check its safety. Finally and most importantly, they publish the results of randomized controlled trials (RCTs). RCTs are studies in which large numbers of patients are randomly allocated to different treatments without the patient or the clinician knowing the allocation and the efficacy of the various treatments compared. RCTs are best way of determining whether a new drug is effective and have to be completed before a drug can be marketed. Because RCTs are very expensive, they are often supported by drug companies. That is, drug companies provide grants or drugs for the trial or assist with data analysis and/or article preparation.
Why Was This Study Done?
Whenever a medical journal publishes an article, the article's authors have to declare any conflicts of interest such as financial gain from the paper's publication. Conflict of interest statements help readers assess papers—an author who owns the patent for a drug, for example, might put an unduly positive spin on his/her results. The experts who review papers for journals before publication provide similar conflict of interest statements. But what about the journal editors who ultimately decide which papers get published? The International Committee of Medical Journal Editors (ICMJE), which produces medical publishing guidelines, states that: “Editors who make final decisions about manuscripts must have no personal, professional, or financial involvement in any of the issues that they might judge.” However, the publication of industry-supported RCTs might create “indirect” conflicts of interest for journals by boosting the journal's impact factor (a measure of a journal's importance based on how often its articles are cited) and its income through the sale of reprints to drug companies. In this study, the researchers investigate whether the publication of industry-supported RCTs influences the impact factors and finances of six major medical journals.
What Did the Researchers Do and Find?
The researchers determined which RCTs published in the New England Journal of Medicine (NEJM), the British Medical Journal (BMJ), The Lancet, and three other major medical journals in 1996–1997 and 2005–2006 were supported wholly, partly, or not at all by industry. They then used the online academic citation index Web of Science to calculate an approximate impact factor for each journal for 1998 and 2007 and calculated the effect of the published RCTs on the impact factor. The proportion of RCTs with sole industry support varied between journals. Thus, 32% of the RCTs published in the NEJM during both two-year periods had industry support whereas only 7% of the RCTs published in the BMJ in 2005–2006 had industry support. Industry-supported trials were more frequently cited than RCTs with other types of support and omitting industry-supported RCTs from impact factor calculations decreased all the approximate journal impact factors. For example, omitting all RCTs with industry or mixed support decreased the 2007 BMJ and NEJM impact factors by 1% and 15%, respectively. Finally, the researchers asked each journal's editor about their journal's income from industry sources. For the BMJ and The Lancet, the only journals that provided this information, income from reprint sales was 3% and 41%, respectively, of total income in 2005–2006.
What Do These Findings Mean?
These findings show that the publication of industry-supported RCTs was associated with an increase in the approximate impact factors of these six major medical journals. Because these journals publish numerous RCTs, this result may not be generalizable to other journals. These findings also indicate that income from reprint sales can be a substantial proportion of a journal's total income. Importantly, these findings do not imply that the decisions of editors are affected by the possibility that the publication of an industry-supported trial might improve their journal's impact factor or income. Nevertheless, the researchers suggest, journals should live up to the same principles related to conflicts of interest as those that they require from their authors and should routinely disclose information on the source and amount of income that they receive.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000354.
This study is further discussed in a PLoS Medicine Perspective by Harvey Marcovitch
The International Committee of Medical Journal Editors provides information about the publication of medical research, including conflicts of interest
The World Association of Medical Editors also provides information on conflicts of interest in medical journals
Information about impact factors is provided by Thomson Reuters, a provider of intelligent information for businesses and professionals; Thomson Reuters also runs Web of Science
doi:10.1371/journal.pmed.1000354
PMCID: PMC2964336  PMID: 21048986
11.  Implementing the 2009 Institute of Medicine recommendations on resident physician work hours, supervision, and safety 
Long working hours and sleep deprivation have been a facet of physician training in the US since the advent of the modern residency system. However, the scientific evidence linking fatigue with deficits in human performance, accidents and errors in industries from aeronautics to medicine, nuclear power, and transportation has mounted over the last 40 years. This evidence has also spawned regulations to help ensure public safety across safety-sensitive industries, with the notable exception of medicine.
In late 2007, at the behest of the US Congress, the Institute of Medicine embarked on a year-long examination of the scientific evidence linking resident physician sleep deprivation with clinical performance deficits and medical errors. The Institute of Medicine’s report, entitled “Resident duty hours: Enhancing sleep, supervision and safety”, published in January 2009, recommended new limits on resident physician work hours and workload, increased supervision, a heightened focus on resident physician safety, training in structured handovers and quality improvement, more rigorous external oversight of work hours and other aspects of residency training, and the identification of expanded funding sources necessary to implement the recommended reforms successfully and protect the public and resident physicians themselves from preventable harm.
Given that resident physicians comprise almost a quarter of all physicians who work in hospitals, and that taxpayers, through Medicare and Medicaid, fund graduate medical education, the public has a deep investment in physician training. Patients expect to receive safe, high-quality care in the nation’s teaching hospitals. Because it is their safety that is at issue, their voices should be central in policy decisions affecting patient safety. It is likewise important to integrate the perspectives of resident physicians, policy makers, and other constituencies in designing new policies. However, since its release, discussion of the Institute of Medicine report has been largely confined to the medical education community, led by the Accreditation Council for Graduate Medical Education (ACGME).
To begin gathering these perspectives and developing a plan to implement safer work hours for resident physicians, a conference entitled “Enhancing sleep, supervision and safety: What will it take to implement the Institute of Medicine recommendations?” was held at Harvard Medical School on June 17–18, 2010. This White Paper is a product of a diverse group of 26 representative stakeholders bringing relevant new information and innovative practices to bear on a critical patient safety problem. Given that our conference included experts from across disciplines with diverse perspectives and interests, not every recommendation was endorsed by each invited conference participant. However, every recommendation made here was endorsed by the majority of the group, and many were endorsed unanimously. Conference members participated in the process, reviewed the final product, and provided input before publication. Participants provided their individual perspectives, which do not necessarily represent the formal views of any organization.
In September 2010 the ACGME issued new rules to go into effect on July 1, 2011. Unfortunately, they stop considerably short of the Institute of Medicine’s recommendations and those endorsed by this conference. In particular, the ACGME only applied the limitation of 16 hours to first-year resident physicans. Thus, it is clear that policymakers, hospital administrators, and residency program directors who wish to implement safer health care systems must go far beyond what the ACGME will require. We hope this White Paper will serve as a guide and provide encouragement for that effort.
Resident physician workload and supervision
By the end of training, a resident physician should be able to practice independently. Yet much of resident physicians’ time is dominated by tasks with little educational value. The caseload can be so great that inadequate reflective time is left for learning based on clinical experiences. In addition, supervision is often vaguely defined and discontinuous. Medical malpractice data indicate that resident physicians are frequently named in lawsuits, most often for lack of supervision. The recommendations are: The ACGME should adjust resident physicians workload requirements to optimize educational value. Resident physicians as well as faculty should be involved in work redesign that eliminates nonessential and noneducational activity from resident physician dutiesMechanisms should be developed for identifying in real time when a resident physician’s workload is excessive, and processes developed to activate additional providersTeamwork should be actively encouraged in delivery of patient care. Historically, much of medical training has focused on individual knowledge, skills, and responsibility. As health care delivery has become more complex, it will be essential to train resident and attending physicians in effective teamwork that emphasizes collective responsibility for patient care and recognizes the signs, both individual and systemic, of a schedule and working conditions that are too demanding to be safeHospitals should embrace the opportunities that resident physician training redesign offers. Hospitals should recognize and act on the potential benefits of work redesign, eg, increased efficiency, reduced costs, improved quality of care, and resident physician and attending job satisfactionAttending physicians should supervise all hospital admissions. Resident physicians should directly discuss all admissions with attending physicians. Attending physicians should be both cognizant of and have input into the care patients are to receive upon admission to the hospitalInhouse supervision should be required for all critical care services, including emergency rooms, intensive care units, and trauma services. Resident physicians should not be left unsupervised to care for critically ill patients. In settings in which the acuity is high, physicians who have completed residency should provide direct supervision for resident physicians. Supervising physicians should always be physically in the hospital for supervision of resident physicians who care for critically ill patientsThe ACGME should explicitly define “good” supervision by specialty and by year of training. Explicit requirements for intensity and level of training for supervision of specific clinical scenarios should be providedCenters for Medicare and Medicaid Services (CMS) should use graduate medical education funding to provide incentives to programs with proven, effective levels of supervision. Although this action would require federal legislation, reimbursement rules would help to ensure that hospitals pay attention to the importance of good supervision and require it from their training programs
Resident physician work hours
Although the IOM “Sleep, supervision and safety” report provides a comprehensive review and discussion of all aspects of graduate medical education training, the report’s focal point is its recommendations regarding the hours that resident physicians are currently required to work. A considerable body of scientific evidence, much of it cited by the Institute of Medicine report, describes deteriorating performance in fatigued humans, as well as specific studies on resident physician fatigue and preventable medical errors.
The question before this conference was what work redesign and cultural changes are needed to reform work hours as recommended by the Institute of Medicine’s evidence-based report? Extensive scientific data demonstrate that shifts exceeding 12–16 hours without sleep are unsafe. Several principles should be followed in efforts to reduce consecutive hours below this level and achieve safer work schedules. The recommendations are: Limit resident physician work hours to 12–16 hour maximum shiftsA minimum of 10 hours off duty should be scheduled between shiftsResident physician input into work redesign should be actively solicitedSchedules should be designed that adhere to principles of sleep and circadian science; this includes careful consideration of the effects of multiple consecutive night shifts, and provision of adequate time off after night work, as specified in the IOM reportResident physicians should not be scheduled up to the maximum permissible limits; emergencies frequently occur that require resident physicians to stay longer than their scheduled shifts, and this should be anticipated in scheduling resident physicians’ work shiftsHospitals should anticipate the need for iterative improvement as new schedules are initiated; be prepared to learn from the initial phase-in, and change the plan as neededAs resident physician work hours are redesigned, attending physicians should also be considered; a potential consequence of resident physician work hour reduction and increased supervisory requirements may be an increase in work for attending physicians; this should be carefully monitored, and adjustments to attending physician work schedules made as needed to prevent unsafe work hours or working conditions for this group“Home call” should be brought under the overall limits of working hours; work load and hours should be monitored in each residency program to ensure that resident physicians and fellows on home call are getting sufficient sleepMedicare funding for graduate medical education in each hospital should be linked with adherence to the Institute of Medicine limits on resident physician work hours
Moonlighting by resident physicians
The Institute of Medicine report recommended including external as well as internal moonlighting in working hour limits. The recommendation is: All moonlighting work hours should be included in the ACGME working hour limits and actively monitored. Hospitals should formalize a moonlighting policy and establish systems for actively monitoring resident physician moonlighting
Safety of resident physicians
The “Sleep, supervision and safety” report also addresses fatigue-related harm done to resident physicians themselves. The report focuses on two main sources of physical injury to resident physicians impaired by fatigue, ie, needle-stick exposure to blood-borne pathogens and motor vehicle crashes. Providing safe transportation home for resident physicians is a logistical and financial challenge for hospitals. Educating physicians at all levels on the dangers of fatigue is clearly required to change driving behavior so that safe hospital-funded transport home is used effectively. Fatigue-related injury prevention (including not driving while drowsy) should be taught in medical school and during residency, and reinforced with attending physicians; hospitals and residency programs must be informed that resident physicians’ ability to judge their own level of impairment is impaired when they are sleep deprived; hence, leaving decisions about the capacity to drive to impaired resident physicians is not recommendedHospitals should provide transportation to all resident physicians who report feeling too tired to drive safely; in addition, although consecutive work should not exceed 16 hours, hospitals should provide transportation for all resident physicians who, because of unforeseen reasons or emergencies, work for longer than consecutive 24 hours; transportation under these circumstances should be automatically provided to house staff, and should not rely on self-identification or request
Training in effective handovers and quality improvement
Handover practice for resident physicians, attendings, and other health care providers has long been identified as a weak link in patient safety throughout health care settings. Policies to improve handovers of care must be tailored to fit the appropriate clinical scenario, recognizing that information overload can also be a problem. At the heart of improving handovers is the organizational effort to improve quality, an effort in which resident physicians have typically been insufficiently engaged. The recommendations are: Hospitals should train attending and resident physicians in effective handovers of careHospitals should create uniform processes for handovers that are tailored to meet each clinical setting; all handovers should be done verbally and face-to-face, but should also utilize written toolsWhen possible, hospitals should integrate hand-over tools into their electronic medical records (EMR) systems; these systems should be standardized to the extent possible across residency programs in a hospital, but may be tailored to the needs of specific programs and services; federal government should help subsidize adoption of electronic medical records by hospitals to improve signoutWhen feasible, handovers should be a team effort including nurses, patients, and familiesHospitals should include residents in their quality improvement and patient safety efforts; the ACGME should specify in their core competency requirements that resident physicians work on quality improvement projects; likewise, the Joint Commission should require that resident physicians be included in quality improvement and patient safety programs at teaching hospitals; hospital administrators and residency program directors should create opportunities for resident physicians to become involved in ongoing quality improvement projects and root cause analysis teams; feedback on successful quality improvement interventions should be shared with resident physicians and broadly disseminatedQuality improvement/patient safety concepts should be integral to the medical school curriculum; medical school deans should elevate the topics of patient safety, quality improvement, and teamwork; these concepts should be integrated throughout the medical school curriculum and reinforced throughout residency; mastery of these concepts by medical students should be tested on the United States Medical Licensing Examination (USMLE) stepsFederal government should support involvement of resident physicians in quality improvement efforts; initiatives to improve quality by including resident physicians in quality improvement projects should be financially supported by the Department of Health and Human Services
Monitoring and oversight of the ACGME
While the ACGME is a key stakeholder in residency training, external voices are essential to ensure that public interests are heard in the development and monitoring of standards. Consequently, the Institute of Medicine report recommended external oversight and monitoring through the Joint Commission and Centers for Medicare and Medicaid Services (CMS). The recommendations are: Make comprehensive fatigue management a Joint Commission National Patient Safety Goal; fatigue is a safety concern not only for resident physicians, but also for nurses, attending physicians, and other health care workers; the Joint Commission should seek to ensure that all health care workers, not just resident physicians, are working as safely as possibleFederal government, including the Centers for Medicare and Medicaid Services and the Agency for Healthcare Research and Quality, should encourage development of comprehensive fatigue management programs which all health systems would eventually be required to implementMake ACGME compliance with working hours a “ condition of participation” for reimbursement of direct and indirect graduate medical education costs; financial incentives will greatly increase the adoption of and compliance with ACGME standards
Future financial support for implementation
The Institute of Medicine’s report estimates that $1.7 billion (in 2008 dollars) would be needed to implement its recommendations. Twenty-five percent of that amount ($376 million) will be required just to bring hospitals into compliance with the existing 2003 ACGME rules. Downstream savings to the health care system could potentially result from safer care, but these benefits typically do not accrue to hospitals and residency programs, who have been asked historically to bear the burden of residency reform costs. The recommendations are: The Institute of Medicine should convene a panel of stakeholders, including private and public funders of health care and graduate medical education, to lay down the concrete steps necessary to identify and allocate the resources needed to implement the recommendations contained in the IOM “Resident duty hours: Enhancing sleep, supervision and safety” report. Conference participants suggested several approaches to engage public and private support for this initiativeEfforts to find additional funding to implement the Institute of Medicine recommendations should focus more broadly on patient safety and health care delivery reform; policy efforts focused narrowly upon resident physician work hours are less likely to succeed than broad patient safety initiatives that include residency redesign as a key componentHospitals should view the Institute of Medicine recommendations as an opportunity to begin resident physician work redesign projects as the core of a business model that embraces safety and ultimately saves resourcesBoth the Secretary of Health and Human Services and the Director of the Centers for Medicare and Medicaid Services should take the Institute of Medicine recommendations into consideration when promulgating rules for innovation grantsThe National Health Care Workforce Commission should consider the Institute of Medicine recommendations when analyzing the nation’s physician workforce needs
Recommendations for future research
Conference participants concurred that convening the stakeholders and agreeing on a research agenda was key. Some observed that some sectors within the medical education community have been reluctant to act on the data. Several logical funders for future research were identified. But above all agencies, Centers for Medicare and Medicaid Services is the only stakeholder that funds graduate medical education upstream and will reap savings downstream if preventable medical errors are reduced as a result of reform of resident physician work hours.
doi:10.2147/NSS.S19649
PMCID: PMC3630963  PMID: 23616719
resident; hospital; working hours; safety
12.  Promotional Tone in Reviews of Menopausal Hormone Therapy After the Women's Health Initiative: An Analysis of Published Articles 
PLoS Medicine  2011;8(3):e1000425.
Adriane Fugh-Berman and colleagues analyzed a selection of published opinion pieces on hormone therapy and show that there may be a connection between receiving industry funding for speaking, consulting, or research and the tone of such opinion pieces.
Background
Even after the Women's Health Initiative (WHI) found that the risks of menopausal hormone therapy (hormone therapy) outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy.
Methods and Findings
We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1) Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2) acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement for scientific accuracy (κ = 0.57) and substantial agreement for promotional tone (κ = 0.65). After discussion, readers found 86% of the articles to be scientifically accurate and 64% to be promotional in tone. Themes that were common in articles considered promotional included attacks on the methodology of the WHI, arguments that clinical trial results should not guide treatment for individuals, and arguments that observational studies are as good as or better than randomized clinical trials for guiding clinical decisions. The promotional articles we identified also implied that the risks associated with hormone therapy have been exaggerated and that the benefits of hormone therapy have been or will be proven. Of the ten authors studied, eight were found to have declared payment for speaking or consulting on behalf of menopausal hormone manufacturers or for research support (seven of these eight were speakers or consultants). Thirty of 32 articles (90%) evaluated as promoting hormone therapy were authored by those with potential financial conflicts of interest, compared to 11 of 18 articles (61%) by those without such conflicts (p = 0.0025). Articles promoting the use of menopausal hormone therapy were 2.41 times (95% confidence interval 1.49–4.93) as likely to have been authored by authors with conflicts of interest as by authors without conflicts of interest. In articles from three authors with conflicts of interest some of the same text was repeated word-for-word in different articles.
Conclusion
There may be a connection between receiving industry funding for speaking, consulting, or research and the publication of promotional opinion pieces on menopausal hormone therapy.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Over the past three decades, menopausal hormones have been heavily promoted for preventing disease in women. However, the Women's Health Initiative (WHI) study—which enrolled more than 26,000 women in the US and which was published in 2004—found that estrogen-progestin and estrogen-only formulations (often prescribed to women around the age of menopause) increased the risk of stroke, deep vein thrombosis, dementia, and incontinence. Furthermore, this study found that the estrogen-progestin therapy increased rates of breast cancer. In fact, the estrogen-progestin arm of the WHI study was stopped in 2002 due to harmful findings, and the estrogen-only arm was stopped in 2004, also because of harmful findings. In addition, the study also found that neither therapy reduced cardiovascular risk or markedly benefited health-related quality of life measures.
Despite these results, two years after the results of WHI study were published, a survey of over 700 practicing gynecologists—the specialists who prescribe the majority of menopausal hormone therapies—in the US found that almost half did not find the findings of the WHI study convincing and that 48% disagreed with the decision to stop the trial early. Furthermore, follow-up surveys found similar results.
Why Was This Study Done?
It is unclear why gynecologists and other physicians continue to prescribe menopausal hormone therapies despite the results of the WHI. Some academics argue that published industry-funded reviews and commentaries may be designed to convey specific, but subtle, marketing messages and several academic analyses have used internal industry documents disclosed in litigation cases. So this study was conducted to investigate whether hormone therapy–promoting tone could be identified in narrative review articles and if so, whether these articles were more likely to have been authored by people who had accepted funding from hormone manufacturers.
What Did the Researchers Do and Find?
The researchers conducted a comprehensive literature search that identified 340 relevant articles published between July 2002 and June 2006—the four years following the cessation of the estrogen-progestin arm of the women's health initiative study. Ten authors had published four to six articles, 47 authored two or three articles, and 371 authored one article each. The researchers focused on authors who had published four or more articles in the four-year period under study and, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. After individually analyzing a batch of articles, the readers met to provide their initial assessments, to discuss them, and to reach consensus on tone and scientific accuracy. Then after the papers were evaluated, each author was identified and the researchers searched for authors' potential financial conflicts of interest, defined as publicly disclosed information that the authors had received payment for research, speaking, or consulting on behalf of a manufacturer of menopausal hormone therapy.
Common themes in the 50 articles included arguments that clinical trial results should not guide treatment for individuals and suggestions that the risks associated with hormone therapy have been exaggerated and that the benefits of hormone therapy have been or will be proven. Furthermore, of the ten authors studied, eight were found to have received payment for research, speaking or consulting on behalf of menopause hormone manufacturers, and 30 of 32 articles evaluated as promoting hormone therapy were authored by those with potential financial conflicts of interest. Articles promoting the use of menopausal hormone therapy were more than twice as likely to have been written by authors with conflicts of interest as by authors without conflicts of interest. Furthermore, Three authors who were identified as having financial conflicts of interest were authors on articles where sections of their previously published articles were repeated word-for-word without citation.
What Do These Findings Mean?
The findings of this study suggest that there may be a link between receiving industry funding for speaking, consulting, or research and the publication of apparently promotional opinion pieces on menopausal hormone therapy. Furthermore, such publications may encourage physicians to continue prescribing these therapies to women of menopausal age. Therefore, physicians and other health care providers should interpret the content of review articles with caution. In addition, medical journals should follow the International Committee of Medical Journal Editors Uniform Requirements for Manuscripts, which require that all authors submit signed statements of their participation in authorship and full disclosure of any conflicts of interest.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000425.
The US National Heart, Lung, and Blood Institute has more information on the Womens Health Initiative
The US National Institutes of Health provide more information about the effects of menopausal hormone replacement therapy
The Office of Women's Health, U.S. Department of Health and Human Services provides information on menopausal hormone therapy
The International Committee of Medical Journal Editors Uniform Requirements for Manuscripts presents Uniform Requirements for Manuscripts published in biomedical journals
The National Womens Health Network, a consumer advocacy group that takes no industry money, has factsheets and articles about menopausal hormone therapy
PharmedOut, a Georgetown University Medical Center project, has many resources on pharmaceutical marketing practices
doi:10.1371/journal.pmed.1000425
PMCID: PMC3058057  PMID: 21423581
13.  Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals 
PLoS Medicine  2013;10(12):e1001566.
Agnes Dechartres and colleagues searched ClinicalTrials.gov for completed drug RCTs with results reported and then searched for corresponding studies in PubMed to evaluate timeliness and completeness of reporting.
Please see later in the article for the Editors' Summary
Background
The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals.
Methods and Findings
We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose).
From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001).
The main study limitation was that we considered only the publication describing the results for the primary outcomes.
Conclusions
Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
When patients consult a doctor, they expect to be recommended what their doctor believes is the most effective treatment with the fewest adverse effects. To determine which treatment to recommend, clinicians rely on sources that include research studies. Among studies, the best evidence is generally agreed to come from systematic reviews and randomized controlled clinical trials (RCTs), studies that test the efficacy and safety of medical interventions by comparing clinical outcomes in groups of patients randomly chosen to receive different interventions. Decision-making based on the best available evidence is called evidence-based medicine. However, evidence-based medicine can only guide clinicians if trial results are published in a timely and complete manner. Unfortunately, underreporting of trials is common. For example, an RCT in which a new drug performs better than existing drugs is more likely to be published than one in which the new drug performs badly or has unwanted adverse effects (publication bias). There can also be a delay in publishing the results of negative trials (time-lag bias) or a failure to publish complete results for all the prespecified outcomes of a trial (reporting bias). All three types of bias threaten informed medical decision-making and the health of patients.
Why Was This Study Done?
One initiative that aims to prevent these biases was included in the 2007 US Food and Drug Administration Amendments Act (FDAAA). The Food and Drug Administration (FDA) is responsible for approving drugs and devices that are marketed in the US. The FDAAA requires that results from clinical trials of FDA-approved drugs and devices conducted in the United States be made publicly available at ClinicalTrials.gov within one year of trial completion. ClinicalTrials.gov—a web-based registry that includes US and international clinical trials—was established in 2000 in response to the 1997 FDA Modernization Act, which required mandatory registration of trial titles and designs and of the conditions and interventions under study. The FDAAA expanded these mandatory requirements by requiring researchers studying FDA-approved drugs and devices to report additional information such as the baseline characteristics of the participants in each arm of the trial and the results of primary and secondary outcome measures (the effects of the intervention on predefined clinical measurements) and their statistical significance (an indication of whether differences in outcomes might have happened by chance). Researchers of other trials registered in ClinicalTrials.gov are welcome to post trial results as well. Here, the researchers compare the timing and completeness (i.e., whether all relevant information was fully reported) of results of drug trials posted at ClinicalTrials.gov with those published in medical journals.
What Did the Researchers Do and Find?
The researchers searched ClinicalTrials.gov for reports of completed phase III and IV (late-stage) RCTs of drugs with posted results. For a random sample of 600 eligible trials, they searched PubMed (a database of biomedical publications) for corresponding publications. Only 50% of trials with results posted at ClinicalTrials.gov had a matching published article. For 202 trials with both posted and published results, the researchers compared the timing and completeness of the results posted at ClinicalTrials.gov and of results reported in the corresponding journal publication. The median time between the study completion date and the first results being publicly posted at ClinicalTrials.gov was 19 months, whereas the time between completion and publication in a journal was 21 months. The flow of participants through trials was completely reported in 64% of the ClinicalTrials.gov postings but in only 48% of the corresponding publications. Results for the primary outcome measure were completely reported in 79% and 69% of the ClinicalTrials.gov postings and corresponding publications, respectively. Finally, adverse events were completely reported in 73% of the ClinicalTrials.gov postings but in only 45% of the corresponding publications, and serious adverse events were reported in 99% and 63% of the ClinicalTrials.gov postings and corresponding publications, respectively.
What Do These Findings Mean?
These findings suggest that the reporting of trial results is significantly more complete at ClinicalTrials.gov than in published journal articles reporting the main trial results. Certain aspects of this study may affect the accuracy of this conclusion. For example, the researchers compared the results posted at ClinicalTrials.gov only with the results in the publication that described the primary outcome of each trial, even though some trials had multiple publications. Importantly, these findings suggest that, to enable patients and physicians to make informed treatment decisions, experts undertaking assessments of drugs should consider seeking efficacy and safety data posted at ClinicalTrials.gov, both for trials whose results are not published yet and for trials whose results are published. Moreover, they suggest that the use of templates to guide standardized reporting of trial results in journals and broader mandatory posting of results may help to improve the reporting and transparency of clinical trials and, consequently, the evidence available to inform treatment of patients.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001566.
Wikipedia has pages on evidence-based medicine and on publication bias (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The US Food and Drug Administration provides information about drug approval in the US for consumers and health-care professionals, plus detailed information on the 2007 Food and Drug Administration Amendments Act
ClinicalTrials.gov provides information about the US National Institutes of Health clinical trial registry, including background information about clinical trials, and a fact sheet detailing the requirements of the 2007 Food and Drug Administration Amendments Act
PLOS Medicine recently launched a Reporting Guidelines Collection, an open access collection of reporting guidelines, commentary, and related research on guidelines from across PLOS journals that aims to help advance the efficiency, effectiveness, and equitability of the dissemination of biomedical information; a 2008 PLOS Medicine editorial discusses the 2007 Food and Drug Administration Amendments Act
doi:10.1371/journal.pmed.1001566
PMCID: PMC3849189  PMID: 24311990
14.  Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data 
PLoS Medicine  2013;10(10):e1001526.
Beate Wieseler and colleagues compare the completeness of reporting of patient-relevant clinical trial outcomes between clinical study reports and publicly available data.
Please see later in the article for the Editors' Summary
Background
Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments.
Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs.
Methods and Findings
We used a sample of 101 trials with full CSRs received for 16 HTAs of drugs completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the CSRs and the publicly available sources of these trials. For each document type we assessed the completeness of information on all patient-relevant outcomes included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health-related quality of life; harm outcomes, e.g., adverse events). We dichotomized the outcomes as “completely reported” or “incompletely reported.” For each document type, we calculated the proportion of outcomes with complete information per outcome category and overall.
We analyzed 101 trials with CSRs; 86 had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs provided complete information on a considerably higher proportion of outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). CSRs also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between CSRs and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes.
The main limitation of our study is that our sample is not representative because only CSRs provided voluntarily by pharmaceutical companies upon request could be assessed. In addition, the sample covered only a limited number of therapeutic areas and was restricted to randomized controlled trials investigating drugs.
Conclusions
In contrast to CSRs, publicly available sources provide insufficient information on patient-relevant outcomes of clinical trials. CSRs should therefore be made publicly available.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
People assume that, when they are ill, health care professionals will ensure that they get the best available treatment. In the past, clinicians used their own experience to make decisions about which treatments to offer their patients, but nowadays, they rely on evidence-based medicine—the systematic review and appraisal of clinical trials, studies that investigate the benefits and harms of drugs and other medical interventions in patients. Evidence-based medicine can guide clinicians, however, only if all the results of clinical research are available for evaluation. Unfortunately, the results of trials in which a new drug performs better than existing drugs are more likely to be published than those in which the new drug performs badly or has unwanted side effects (publication bias). Moreover, trial outcomes that support the use of a new treatment are more likely to be published than those that do not support its use (outcome reporting bias). Both types of bias pose a substantial threat to informed medical decision-making.
Why Was This Study Done?
Recent initiatives, such as making registration of clinical trials in a trial registry (for example, ClinicalTrials.gov) a precondition for publication in medical journals, aim to prevent these biases but are imperfect. Another way to facilitate the unbiased evaluation of clinical research might be to increase access to clinical study reports (CSRs)—detailed but generally unpublished accounts of clinical trials. Notably, information from CSRs was recently used to challenge conclusions based on published evidence about the efficacy and safety of the antiviral drug oseltamivir and the antidepressant reboxetine. In this study, the researchers compare the information available in CSRs and in publicly available sources (journal publications and registry reports) for the patient-relevant outcomes included in 16 health technology assessments (HTAs; analyses of the medical implications of the use of specific medical technologies) for drugs; the HTAs were prepared by the Institute for Quality and Efficiency in Health Care (IQWiG), Germany's main HTA agency.
What Did the Researchers Do and Find?
The researchers searched for published journal articles and registry reports for each of 101 trials for which the IQWiG had requested and received full CSRs from drug manufacturers during HTA preparation. They then assessed the completeness of information on the patient-relevant benefit and harm outcomes (for example symptom relief and adverse effects, respectively) included in each document type. Eighty-six of the included trials had at least one publicly available data source; the results of 15% of the trials were not available in either journals or registry reports. Overall, the CSRs provided complete information on 86% of the patient-related outcomes, whereas the combined publicly available sources provided complete information on only 39% of the outcomes. For individual outcomes, the CSRs provided complete information on 78%–100% of the benefit outcomes, with the exception of health-related quality of life (57%); combined publicly available sources provided complete information on 20%–53% of these outcomes. The CSRs also provided more information on patient-relevant harm outcomes than the publicly available sources.
What Do These Findings Mean?
These findings show that, for the clinical trials considered here, publicly available sources provide much less information on patient-relevant outcomes than CSRs. The generalizability of these findings may be limited, however, because the trials included in this study are not representative of all trials. Specifically, only CSRs that were voluntarily provided by drug companies were assessed, a limited number of therapeutic areas were covered by the trials, and the trials investigated only drugs. Nevertheless, these findings suggest that access to CSRs is important for the unbiased evaluation of clinical trials and for informed decision-making in health care. Notably, in June 2013, the European Medicines Agency released a draft policy calling for the proactive publication of complete clinical trial data (possibly including CSRs). In addition, the European Union and the European Commission are considering legal measures to improve the transparency of clinical trial data. Both these initiatives will probably only apply to drugs that are approved after January 2014, however, and not to drugs already in use. The researchers therefore call for CSRs to be made publicly available for both past and future trials, a recommendation also supported by the AllTrials initiative, which is campaigning for all clinical trials to be registered and fully reported.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001526.
Wikipedia has pages on evidence-based medicine, publication bias, and health technology assessment (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The ClinicalTrials.gov website is a searchable register of federally and privately supported clinical trials in the US; it provides information about all aspects of clinical trials
The European Medicines Agency (EMA) provides information about all aspects of the scientific evaluation and approval of new medicines in the European Union, and guidance on the preparation of clinical study reports; its draft policy on the release of data from clinical trials is available
Information about IQWiG is available (in English and German); Informed Health Online is a website provided by IQWiG that provides objective, independent, and evidence-based information for patients (also in English and German)
doi:10.1371/journal.pmed.1001526
PMCID: PMC3793003  PMID: 24115912
15.  The 50 Most-cited Articles in Orthopaedic Surgery From Mainland China 
Background
Citation analysis has been widely used to evaluate the impact of articles in medical and surgical specialties. Although China is the most populous country in the world, and although more than 50,000 orthopaedic surgeons practice there, to our knowledge no formal citation analysis of Chinese orthopaedic articles has been performed.
Questions/purposes
We identified the 50 most-cited orthopaedic articles from mainland China and evaluated these articles in terms of their language of publication, source journals, and topics.
Methods
Science Citation Index Expanded was searched in July 31, 2014 for citations of articles published in 70 selected journals since the inception of the database. The 50 most-cited orthopaedic articles originating in mainland China were identified. Basic information, including title, authors, year of publication, article type, journal in which the work was published, city, institution, number of citations, decade published, and topic or subspecialty of the research were recorded.
Results
The number of citations for the top 50 papers ranged from 181 to 31 (mean, 52). These articles were published between 1981 and 2010. The decade of 2000 to 2009 was the most prolific, with 36 of the top 50 articles published during this time. All articles were written in English and they were published in a total of 16 journals. The journal Spine published the largest number of articles (12), followed by Clinical Orthopaedics and Related Research® (seven). The journal Lancet had the highest impact factor (39.207 for 2013) among any of the journals that published articles we identified. The top 50 articles originated mainly from Beijing (16) and Shanghai (12), with basic research being the focus of the majority (27 of 50; 54%); the remaining were clinical studies. Bone was the most-investigated topic in basic research; the spine was the most-common topic among the identified clinical studies.
Conclusions
The 50 most-cited articles that we identified should be considered influential, although a large gap remains between mainland China and the global orthopaedic community in terms of citations per article. Nevertheless, insofar as the most-recent decade of our survey generated the most articles in this top-50 list, we would characterize mainland China’s effect on musculoskeletal research as increasing, and as funding increases to programs in mainland China, we anticipate this trend will continue in the future.
doi:10.1007/s11999-015-4132-1
PMCID: PMC4457774  PMID: 25589444
16.  Characteristics and Trends of Orthopedic Publications between 2000 and 2009 
Clinics in Orthopedic Surgery  2011;3(3):225-229.
Background
This study was undertaken to investigate the trends of orthopedic publications during the last decade, and to document the country of origin, journal, funding source, and language of contribution using PubMed.
Methods
Orthopedic articles published between 2000 and 2009 were retrieved from PubMed using the following search terms: "orthopaedic[Affiliation] AND ("2000/1/1"[PDAT]: "2009/12/31"[PDAT])" and "orthopedic[Affiliation] AND ("2000/1/1"[PDAT]: "2009/12/31"[PDAT])." The articles were downloaded in XML file format, which contained the following information: article title, author names, journal names, publication dates, article types, languages, authors' affiliations and funding sources. These information was extracted, sorted, and rearranged using the database's management software. We investigated the annual number of published orthopedic articles worldwide and the annual rate of increase. Furthermore, the country of publication origin, journal, funding source, and language of contribution were also investigated.
Results
A total of 46,322 orthopedic articles were published and registered in PubMed in the last 10 years. The worldwide number of published orthopedic articles increased from 2,889 in 2000 to 6,909 in 2009, showing an annual increase of 384.6 articles, or an annualized compound rate of 10.2%. The United States ranked highest in the number of published orthopedic articles, followed by Japan, the United Kingdom, Germany, and the Republic of Korea. Among the orthopedic articles published worldwide during the last 10 years, 37.9% pertained studies performed in the United States. Fifty-seven point three percent (57.3%) of articles were published in journals established in the United States. Among the published orthopaedic articles, 4,747 articles (10.2%) disclosed financial support by research funds, of which 4,688 (98.8%) articles utilized research funds from the United States. Most articles were published in English (97.2%, 45,030 articles).
Conclusions
The number of published orthopedic articles has been increasing over the last decade. The number of orthopedic articles, journals publication, and funding sources were dominated by research conducted in the United States, while share and growth of Asian countries including Japan, the Republic of Korea, and China were notable.
doi:10.4055/cios.2011.3.3.225
PMCID: PMC3162203  PMID: 21909470
Bibliometrics; Orthopedics; Research trend; Periodicals as topics
17.  Sri Lanka in global medical research: a scientific analysis of the Sri Lankan research output during 2000-2009 
BMC Research Notes  2012;5:121.
Background
Scientific research is an essential component in guiding improvements in health systems. There are no studies examining the Sri Lankan medical research output at international level. The present study evaluated the Sri Lankan research performance in medicine as reflected by the research publications output between years 2000-2009.
Methods
This study was based on Sri Lankan medical research publication data, retrieved from the SciVerse Scopus® from January 2000 to December 2009. The process of article selection was as follows: Affiliation - 'Sri Lanka' or 'Ceylon', Publication year - 'January 2000 to December 2009' and Subject area - 'Life and Health Sciences'. The articles identified were classified according to disease, medical speciality, institutions, major international collaborators, authors and journals.
Results
Sri Lanka's cumulative medical publications output between years 2000-2009 was 1,740 articles published in 160 different journals. The average annual publication growth rate was 9.1%. Majority of the articles were published in 'International' (n = 950, 54.6%) journals. Most articles were descriptive studies (n = 611, 35.1%), letters (n-345, 19.8%) and case reports (n = 311, 17.9%). The articles were authored by 148 different Sri Lankan authors from 146 different institutions. The three most prolific local institutions were Universities of; Colombo (n = 547), Kelaniya (n = 246) and Peradeniya (n = 222). Eighty four countries were found to have published collaborative papers with Sri Lankan authors during the last decade. UK was the largest collaborating partner (n = 263, 15.1%).
Malaria (n = 75), Diabetes Mellitus (n = 55), Dengue (n = 53), Accidental injuries (n = 42) and Lymphatic filariasis (n = 40) were the major diseases studied. The 1,740 publications were cited 9,708 times, with an average citation of 5.6 per paper. The most cited paper had 203 citations, while there were 597 publications with no citations. The Sri Lankan authors' contribution to the global medical research output during the last decade was only 0.086%.
Conclusion
The Sri Lankan medical research output during the last decade is only a small fraction of the global research output. There it is a necessity to setup an enabling environment for research, with a proper vision, support, funds and training. In addition, collaborations across the region need to be strengthened to face common regional health challenges.
doi:10.1186/1756-0500-5-121
PMCID: PMC3305378  PMID: 22364509
Sri Lanka; Medical research; Publication; Analysis
18.  Trial Publication after Registration in ClinicalTrials.Gov: A Cross-Sectional Analysis 
PLoS Medicine  2009;6(9):e1000144.
Joseph Ross and colleagues examine publication rates of clinical trials and find low rates of publication even following registration in Clinicaltrials.gov.
Background
ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication.
Methods and Findings
We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006).
Conclusions
Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
People assume that whenever they are ill, health care professionals will make sure they get the best available treatment. But how do clinicians know which treatment is most appropriate? In the past, clinicians used their own experience to make treatment decisions. Nowadays, they rely on evidence-based medicine—the systematic review and appraisal of the results of clinical trials, studies that investigate the efficacy and safety of medical interventions in people. However, evidence-based medicine can only be effective if all the results from clinical trials are published promptly in medical journals. Unfortunately, the results of trials in which a new drug did not perform better than existing drugs or in which it had unwanted side effects often remain unpublished or only appear in the public domain many years after the drug has been approved for clinical use by the US Food and Drug Administration (FDA) and other governmental bodies.
Why Was This Study Done?
The extent of this “selective” publication, which can impair evidence-based clinical practice, remains unclear but is thought to be substantial. In this study, the researchers investigate the problem of selective publication by systematically examining the extent of publication of the results of trials registered in ClinicalTrials.gov, a Web-based registry of US and international clinical trials. ClinicalTrials.gov was established in 2000 by the US National Library of Medicine in response to the 1997 FDA Modernization Act. This act required preregistration of all trials of new drugs to provide the public with information about trials in which they might be able to participate. Mandatory data elements for registration in ClinicalTrials.gov initially included the trial's title, the condition studied in the trial, the trial design, and the intervention studied. In September 2007, the FDA Amendments Act expanded the mandatory requirements for registration in ClinicalTrials.gov by making it necessary, for example, to report the trial start date and to report primary and secondary outcomes (the effect of the intervention on predefined clinical measurements) in the registry within 2 years of trial completion.
What Did the Researchers Do and Find?
The researchers identified 7,515 trials that were registered within ClinicalTrials.gov after December 31, 1999 (excluding phase I, safety trials), and whose record indicated trial completion by June 8, 2007. Most of these trials reported all the mandatory data elements that were required by ClinicalTrials.gov before the FDA Amendments Act but reporting of optional data elements was less complete. For example, only two-thirds of the trials reported their primary outcome. Next, the researchers randomly selected 10% of the trials and, after excluding trials whose completion date was after December 31, 2005 (to allow at least two years for publication), determined the publication status of this subsample by systematically searching MEDLINE (an online database of articles published in selected medical and scientific journals). Fewer than half of the trials in the subsample had been published, and the citation for only a third of these publications had been entered into ClinicalTrials.gov. Only 40% of industry-sponsored trials had been published compared to 56% of nonindustry/nongovernment-sponsored trials, a difference that is unlikely to have occurred by chance. Finally, 61% of trials with a completion date before 2004 had been published, but only 42% of trials completed during 2005 had been published.
What Do These Findings Mean?
These findings indicate that, over the period studied, critical trial information was not included in the ClinicalTrials.gov registry. The FDA Amendments Act should remedy some of these shortcomings but only if the accuracy and completeness of the information in ClinicalTrials.gov is carefully monitored. These findings also reveal that registration in ClinicalTrials.gov does not guarantee that trial results will appear in a timely manner in the scientific literature. However, they do not address the reasons for selective publication (which may be, in part, because it is harder to publish negative results than positive results), and they are potentially limited by the methods used to discover whether trial results had been published. Nevertheless, these findings suggest that the FDA, trial sponsors, and the scientific community all need to make a firm commitment to minimize the selective publication of trial results to ensure that patients and clinicians have access to the information they need to make fully informed treatment decisions.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000144.
PLoS Medicine recently published two related articles on selected publication by Ida Sim and colleagues and by Lisa Bero and colleagues and an editorial discussing the FDA Amendments Act
ClinicalTrials.gov provides information about the US National Institutes of Health clinical trial registry, including background information about clinical trials, and a fact sheet detailing the requirements of the FDA Amendments Act 2007 for trial registration
The US Food and Drug Administration provides further information about drug approval in the US for consumers and health care professionals
doi:10.1371/journal.pmed.1000144
PMCID: PMC2728480  PMID: 19901971
19.  Relationship between Funding Source and Conclusion among Nutrition-Related Scientific Articles 
PLoS Medicine  2007;4(1):e5.
Background
Industrial support of biomedical research may bias scientific conclusions, as demonstrated by recent analyses of pharmaceutical studies. However, this issue has not been systematically examined in the area of nutrition research. The purpose of this study is to characterize financial sponsorship of scientific articles addressing the health effects of three commonly consumed beverages, and to determine how sponsorship affects published conclusions.
Methods and Findings
Medline searches of worldwide literature were used to identify three article types (interventional studies, observational studies, and scientific reviews) about soft drinks, juice, and milk published between 1 January, 1999 and 31 December, 2003. Financial sponsorship and article conclusions were classified by independent groups of coinvestigators. The relationship between sponsorship and conclusions was explored by exact tests and regression analyses, controlling for covariates. 206 articles were included in the study, of which 111 declared financial sponsorship. Of these, 22% had all industry funding, 47% had no industry funding, and 32% had mixed funding. Funding source was significantly related to conclusions when considering all article types (p = 0.037). For interventional studies, the proportion with unfavorable conclusions was 0% for all industry funding versus 37% for no industry funding (p = 0.009). The odds ratio of a favorable versus unfavorable conclusion was 7.61 (95% confidence interval 1.27 to 45.73), comparing articles with all industry funding to no industry funding.
Conclusions
Industry funding of nutrition-related scientific articles may bias conclusions in favor of sponsors' products, with potentially significant implications for public health.
In 111 scientific articles on nonalcoholic beverages, articles with all industry funding were more than 7 times more likely to have favorable conclusions compared with articles with no industry funding.
Editors' Summary
Background.
Much of the money available for doing medical research comes from companies, as opposed to government agencies or charities. There is some evidence that when a research study is sponsored by an organization that has a financial interest in the outcome, the study is more likely to produce results that favor the funder (this is called “sponsorship bias”). This phenomenon is worrying, because if our knowledge about effectiveness and safety of medicines is based on biased findings, patients could suffer. However, it is not clear whether sponsorship bias extends beyond research into drugs, but also affects other types of research that is in the public interest. For example, research into the health benefits, or otherwise, of different types of food and drink may affect government guidelines, regulations, and the behavior patterns of members of the public. Were sponsorship bias also to exist in this area of research, the health of the wider public could be affected.
Why Was This Study Done?
There is not a great deal of evidence about whether sponsorship bias affects nutritional research (scientific studies that look at the relationship between food and/or drink, and health or disease states). Therefore, the group of researchers here set out to collect information from published nutritional research papers, to see if the type of sponsorship for the research studies was in any way linked with whether the main conclusions were favorable or unfavorable to the sponsor.
What Did the Researchers Do and Find?
The research study reported here used the scientific literature as a source of data. The researchers chose to examine one particular area of nutrition (nonalcoholic drinks including soft drinks, juices, and milk), so that their investigation would not be affected too much by variability between the different types of nutritional research. Using literature searches, the researchers identified all original research and scientific review articles published between January 1999 and December 2003 that examined soft drinks, juices, and milk; described research carried out in humans; and at the same time drew conclusions relevant to health or disease. Then, information from each published article was categorized: the conclusions were coded as either favorable, unfavorable, or neutral in relation to the health effects of the products being studied, and the article's funding was coded as either all industry (ie, food/drinks companies), no industry, or mixed. 206 published articles were analyzed and only 54% declared funding. The researchers found that, overall, there was a strong association between the type of funding available for these articles and the conclusions that were drawn. Articles sponsored exclusively by food/drinks companies were four to eight times more likely to have conclusions favorable to the financial interests of the sponsoring company than articles which were not sponsored by food or drinks companies.
What Do These Findings Mean?
These findings suggest that a high potential for bias exists in research into the health benefits or harms of nonalcoholic drinks. It is not clear from this research study why or how this bias comes about, but there are many different mechanisms that might cause it. The researchers suggest that certain initiatives might help to reduce bias, for example, increasing independent funding of nutrition research.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/doi:10.1371/journal.pmed.0040005.
Conflict of Interest definition from Wikipedia (Wikipedia is an internet encyclopedia that anyone can edit)
The International Committee of Medical Journal Editors provides standard guidelines for practices at medical journals, including a section on sponsorship, authorship, and accountability
The Committee on Publication Ethics is a forum for journal editors to discuss issues related to the integrity of the scientific record, and it provides guidelines for editors and case studies for reference
The Good Publication Practice guidelines outline standards for responsible publication of research sponsored by pharmaceutical companies
doi:10.1371/journal.pmed.0040005
PMCID: PMC1764435  PMID: 17214504
20.  Physician Emigration from Sub-Saharan Africa to the United States: Analysis of the 2011 AMA Physician Masterfile 
PLoS Medicine  2013;10(9):e1001513.
Siankam Tankwanchi and colleagues used the AMA Physician Masterfile and the WHO Global Health Workforce Statistics on physicians in sub-Saharan Africa to determine trends in physician emigration to the United States.
Please see later in the article for the Editors' Summary
Background
The large-scale emigration of physicians from sub-Saharan Africa (SSA) to high-income nations is a serious development concern. Our objective was to determine current emigration trends of SSA physicians found in the physician workforce of the United States.
Methods and Findings
We analyzed physician data from the World Health Organization (WHO) Global Health Workforce Statistics along with graduation and residency data from the 2011 American Medical Association Physician Masterfile (AMA-PM) on physicians trained or born in SSA countries who currently practice in the US. We estimated emigration proportions, year of US entry, years of practice before emigration, and length of time in the US. According to the 2011 AMA-PM, 10,819 physicians were born or trained in 28 SSA countries. Sixty-eight percent (n = 7,370) were SSA-trained, 20% (n = 2,126) were US-trained, and 12% (n = 1,323) were trained outside both SSA and the US. We estimated active physicians (age ≤70 years) to represent 96% (n = 10,377) of the total. Migration trends among SSA-trained physicians increased from 2002 to 2011 for all but one principal source country; the exception was South Africa whose physician migration to the US decreased by 8% (−156). The increase in last-decade migration was >50% in Nigeria (+1,113) and Ghana (+243), >100% in Ethiopia (+274), and >200% (+244) in Sudan. Liberia was the most affected by migration to the US with 77% (n = 175) of its estimated physicians in the 2011 AMA-PM. On average, SSA-trained physicians have been in the US for 18 years. They practiced for 6.5 years before US entry, and nearly half emigrated during the implementation years (1984–1999) of the structural adjustment programs.
Conclusion
Physician emigration from SSA to the US is increasing for most SSA source countries. Unless far-reaching policies are implemented by the US and SSA countries, the current emigration trends will persist, and the US will remain a leading destination for SSA physicians emigrating from the continent of greatest need.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Population growth and aging and increasingly complex health care interventions, as well as existing policies and market forces, mean that many countries are facing a shortage of health care professionals. High-income countries are addressing this problem in part by encouraging the immigration of foreign health care professionals from low- and middle-income countries. In the US, for example, international medical graduates (IMGs) can secure visas and permanent residency by passing examinations provided by the Educational Commission of Foreign Medical Graduates and by agreeing to provide care in areas that are underserved by US physicians. Inevitably, the emigration of physicians from low- and middle-income countries undermines health service delivery in the emigrating physicians' country of origin because physician supply is already inadequate in those countries. Physician emigration from sub-Saharan Africa, which has only 2% of the global physician workforce but a quarter of the global burden of disease, is particularly worrying. Since 1970, as a result of large-scale emigration and limited medical education, there has been negligible or negative growth in the density of physicians in many countries in sub-Saharan Africa. In Liberia, for example, in 1973, there were 7.76 physicians per 100,000 people but by 2008 there were only 1.37 physicians per 100,000 people; in the US, there are 250 physicians per 100,000 people.
Why Was This Study Done?
Before policy proposals can be formulated to address global inequities in physician distribution, a clear picture of the patterns of physician emigration from resource-limited countries is needed. In this study, the researchers use data from the 2011 American Medical Association Physician Masterfile (AMA-PM) to investigate the “brain drain” of physicians from sub-Saharan Africa to the US. The AMA-PM collects annual demographic, academic, and professional data on all residents (physicians undergoing training in a medical specialty) and licensed physicians who practice in the US.
What Did the Researchers Do and Find?
The researchers used data from the World Health Organization (WHO) Global Health Workforce Statistics and graduation and residency data from the 2011 AMA-PM to estimate physician emigration rates from sub-Saharan African countries, year of US entry, years of service provided before emigration to the US, and length of time in the US. There were 10,819 physicians who were born or trained in 28 sub-Saharan African countries in the 2011 AMA-PM. By using a published analysis of the 2002 AMA-PM, the researchers estimated that US immigration among sub-Saharan African-trained physicians had increased over the past decade for all the countries examined except South Africa, where physician emigration had decreased by 8%. Overall, the number of sub-Saharan African IMGs in the US had increased by 38% since 2002. More than half of this increase was accounted for by Nigerian IMGs. Liberia was the country most affected by migration of its physicians to the US—77% of its estimated 226 physicians were in the 2011 AMA-PM. On average, sub-Saharan African IMGs had been in the US for 18 years and had practiced for 6.5 years before emigration. Finally, nearly half of the sub-Saharan African IMGs had migrated to US between 1984 and 1995, years during which structural adjustment programs, which resulted in deep cuts to public health care services, were implemented in developing countries by international financial institutions as conditions for refinancing.
What Do These Findings Mean?
Although the sub-Saharan African IMGs in the 2011 AMA-PM only represent about 1% of all the physicians and less than 5% of the IMGs in the AMA-PM, these findings reveal a major loss of physicians from sub-Saharan Africa. They also suggest that emigration of physicians from sub-Saharan Africa is a growing problem and is likely to continue unless job satisfaction for physicians is improved in their country of origin. Moreover, because the AMA-PM only lists physicians who qualify for a US residency position, more physicians may have moved from sub-Saharan Africa to the US than reported here and may be working in other jobs incommensurate with their medical degrees (“brain waste”). The researchers suggest that physician emigration from sub-Saharan Africa to the US reflects the complexities in the labor markets for health care professionals in both Africa and the US and can be seen as low- and middle-income nations subsidizing the education of physicians in high-income countries. Policy proposals to address global inequities in physician distribution will therefore need both to encourage the recruitment, training, and retention of health care professionals in resource-limited countries and to persuade high-income countries to train more home-grown physicians to meet the needs of their own populations.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001513.
The Foundation for Advancement of International Medical Education and Research is a non-profit foundation committed to improving world health through education that was established in 2000 by the Educational Commission for Foreign Medical Graduates
The Global Health Workforce Alliance is a partnership of national governments, civil society, international agencies, finance institutions, researchers, educators, and professional associations dedicated to identifying, implementing and advocating for solutions to the chronic global shortage of health care professionals (available in several languages)
Information on the American Medical Association Physician Masterfile and the providers of physician data lists is available via the American Medical Associations website
The World Health Organization (WHO) annual World Health Statistics reports present the most recent health statistics for the WHO Member States
The Medical Education Partnership Initiative is a US-sponsored initiative that supports medical education and research in sub-Saharan African institutions, aiming to increase the quantity, quality, and retention of graduates with specific skills addressing the health needs of their national populations
CapacityPlus is the USAID-funded global project uniquely focused on the health workforce needed to achieve the Millennium Development Goals
Seed Global Health cultivates the next generation of health professionals by allying medical and nursing volunteers with their peers in resource-limited settings
"America is Stealing the Worlds Doctors", a 2012 New York Times article by Matt McAllester, describes the personal experience of a young doctor who emigrated from Zambia to the US
Path to United States Practice Is Long Slog to Foreign Doctors, a 2013 New York Times article by Catherine Rampell, describes the hurdles that immigrant physicians face in practicing in the US
doi:10.1371/journal.pmed.1001513
PMCID: PMC3775724  PMID: 24068894
21.  Statistical relationships between journal use and research output at academic institutions in South Korea 
Scientometrics  2015;103(3):751-777.
In this study, we analysed the statistical association between e-journal use and research output at the institution level in South Korea by performing comparative and diachronic analyses, as well as the analysis by field. The datasets were compiled from four different sources: national reports on research output indicators in science fields, two statistics databases on higher education institutions open to the public, and e-journal usage statistics generated by 47 major publishers. Due to the different data sources utilized, a considerable number of missing values appeared in our datasets and various mapping issues required corrections prior to the analysis. Two techniques for handling missing data were applied and the impact of each technique was discussed. In order to compile the institutional data by field, journals were first mapped, and then the statistics were summarized according to subject field. We observed that e-journal use exhibited stronger correlations with the number of publications and the times cited, in contrast to the number of undergraduates, graduates, faculty members and the amount of research funds, and this was the case regardless of the NA handling method or author type. The difference between the maximum correlation for the amount of external research funding with two average indicators and that of the correlation for e-journal use were not significant. Statistically, the accountability of e-journal use for the average times cited per article and the average JIF was quite similar with external research funds. It was found that the number of e-journal articles used had a strong positive correlation (Pearson’s correlation coefficients of r > 0.9, p < 0.05) with the number of articles published in SCI(E) journals and the times cited regardless of the author type, NA handling method or time period. We also observed that the top-five institutions in South Korea, with respect to the number of publications in SCI(E) journals, were generally across a balanced range of academic activities, while producing significant research output and using published material. Finally, we confirmed that the association of e-journal use with the two quantitative research indicators is strongly positive, even for the analyses by field, with the exception of the Arts and Humanities.
doi:10.1007/s11192-015-1563-0
PMCID: PMC4430588  PMID: 25995527
Correlation analysis; Comparative analysis; Diachronic analysis; e-Journal use; Research output
22.  International Funding for Malaria Control in Relation to Populations at Risk of Stable Plasmodium falciparum Transmission 
PLoS Medicine  2008;5(7):e142.
Background
The international financing of malaria control has increased significantly in the last ten years in parallel with calls to halve the malaria burden by the year 2015. The allocation of funds to countries should reflect the size of the populations at risk of infection, disease, and death. To examine this relationship, we compare an audit of international commitments with an objective assessment of national need: the population at risk of stable Plasmodium falciparum malaria transmission in 2007.
Methods and Findings
The national distributions of populations at risk of stable P. falciparum transmission were projected to the year 2007 for each of 87 P. falciparum–endemic countries. Systematic online- and literature-based searches were conducted to audit the international funding commitments made for malaria control by major donors between 2002 and 2007. These figures were used to generate annual malaria funding allocation (in US dollars) per capita population at risk of stable P. falciparum in 2007. Almost US$1 billion are distributed each year to the 1.4 billion people exposed to stable P. falciparum malaria risk. This is less than US$1 per person at risk per year. Forty percent of this total comes from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Substantial regional and national variations in disbursements exist. While the distribution of funds is found to be broadly appropriate, specific high population density countries receive disproportionately less support to scale up malaria control. Additionally, an inadequacy of current financial commitments by the international community was found: under-funding could be from 50% to 450%, depending on which global assessment of the cost required to scale up malaria control is adopted.
Conclusions
Without further increases in funding and appropriate targeting of global malaria control investment it is unlikely that international goals to halve disease burdens by 2015 will be achieved. Moreover, the additional financing requirements to move from malaria control to malaria elimination have not yet been considered by the scientific or international community.
To reach global malaria control goals, Robert Snow and colleagues argue that more international funding is needed but that it must be targeted at specific countries most at risk.
Editors' Summary
Background.
Malaria is one of the most common infectious diseases in the world and one of the greatest global public health problems. The Plasmodium falciparum parasite causes approximately 500 million cases each year and over one million deaths. More than 40% of the world's population is at risk of malaria.
The Millennium Development Goals (MDGs), established by the United Nations in 2000, include a target in Goal 6: “to have halted by 2015 and begun to reverse the incidence of malaria and other major diseases.” Following the launch of the MDG and international initiatives like Roll Back Malaria, there has been an upsurge in support for malaria control. This effort has included the formation of the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) and considerable funding from the US President's Malaria Initiative, the World Bank, the UK Department for International Development, USAID, and nongovernmental agencies and foundations like the Bill & Melinda Gates Foundation. But it is not yet clear how equitable or effective the financial commitments to malaria control have been.
Why Was This Study Done?
As part of the activities of the Malaria Atlas Project, the researchers had previously generated a global map of the limits of P. falciparum transmission. This map detailed areas where risk is moderate or high (stable transmission areas where malaria is endemic) and areas where the risk of transmission is low (unstable transmission areas where sporadic outbreaks of malaria may occur). Because the level of funding to control malaria should be proportionate to the size of the populations at risk, the researchers in this study appraised whether the areas of greatest need were receiving financial resources in proportion to this risk. That is, whether there is equity in how malaria funding is allocated.
What Did the Researchers Do and Find?
To assess the international financing of malaria control, the researchers conducted a audit of financial commitments to malaria control of the GFATM, national governments, and other donors for the period 2002 to 2007. To assess need, they estimated the population at risk of stable P. falciparum malaria transmission in 2007, building on their previous malaria map. Financial commitments were identified via online and literature searches, including the GFATM Web site, the World Malaria Report produced by WHO and UNICEF, and various other sources of financial information. Together these data allowed the authors to generate an estimate of the annual malaria funding allocation per capita population at risk of P. falciparum.
Of the 87 malaria-endemic countries, 76 received malaria funding commitments by the end of 2007. Overall, annual funding amounted to US$1 billion dollars, or less than US$1 per person at risk. Forty percent came from the GFATM, and the remaining from a mix of national government and external donors. The authors found great regional variation in the levels of funding. For example, looking at just the countries approved for GFATM funding, Myanmar was awarded an average annual per capita-at-risk amount of US$0.01 while Suriname was awarded US$147. With all financial commitments combined, ten countries had per capita annual support of more than US$4 per person, but 34 countries had less than US$1, including 16 where annual malaria support was less than US$0.5 per capita. These 16 countries represent 50% of the global population at risk and include seven of the poorest countries in Africa and two of the most densely populated stable endemic countries in the world (India and Indonesia).
What Do These Findings Mean?
The researchers find that the distribution of funds across the regions affected by malaria to be generally appropriate, with the Africa region and low-population-at-risk areas such as the Americas, the Caribbean, the Middle East, and Eastern Europe receiving proportionate annual malaria support. But they also identify large shortfalls, such as in the South East Asia and Western Pacific regions, which represents 47% of the global population at risk but received only 17% of GFATM and 24% of non-GFATM support. National government spending also falls short: for example, in Nigeria, where more than 100 million people are at risk of stable P. falciparum transmission, less than US$1 is invested per person per year. These findings illustrate how important it is to examine financial commitments against actual needs. Given the gaps between funding support and level of stable P. falciparum risk, the authors conclude that the goal to reduce the global burden of malaria by 2015 very likely will not be met with current commitments. They estimate that there remains a 50%–450% shortfall in funding needed to scale up malaria control worldwide.
Future research should assess the impact of these funding commitments and what additional resources will be needed if goals of malaria elimination are added to malaria control targets.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050142.
This study is discussed further in a PLoS Medicine Perspective by Anthony Kiszewski
The authors of this article have also published a global map of malaria risk; see Guerra, et al. (2008) PLoS Med 5(2) e38
Information is available from the Global Fund to Fight AIDS, Tuberculosis and Malaria
More information is available on global mapping of malaria risk from the Malaria Atlas Project
doi:10.1371/journal.pmed.0050142
PMCID: PMC2488181  PMID: 18651785
23.  Misrepresentation of Randomized Controlled Trials in Press Releases and News Coverage: A Cohort Study 
PLoS Medicine  2012;9(9):e1001308.
A study conducted by Amélie Yavchitz and colleagues examines the factors associated with “spin” (specific reporting strategies, intentional or unintentional, that emphasize the beneficial effect of treatments) in press releases of clinical trials.
Background
Previous studies indicate that in published reports, trial results can be distorted by the use of “spin” (specific reporting strategies, intentional or unintentional, emphasizing the beneficial effect of the experimental treatment). We aimed to (1) evaluate the presence of “spin” in press releases and associated media coverage; and (2) evaluate whether findings of randomized controlled trials (RCTs) based on press releases and media coverage are misinterpreted.
Methods and Findings
We systematically searched for all press releases indexed in the EurekAlert! database between December 2009 and March 2010. Of the 498 press releases retrieved and screened, we included press releases for all two-arm, parallel-group RCTs (n = 70). We obtained a copy of the scientific article to which the press release related and we systematically searched for related news items using Lexis Nexis.
“Spin,” defined as specific reporting strategies (intentional or unintentional) emphasizing the beneficial effect of the experimental treatment, was identified in 28 (40%) scientific article abstract conclusions and in 33 (47%) press releases. From bivariate and multivariable analysis assessing the journal type, funding source, sample size, type of treatment (drug or other), results of the primary outcomes (all nonstatistically significant versus other), author of the press release, and the presence of “spin” in the abstract conclusion, the only factor associated, with “spin” in the press release was “spin” in the article abstract conclusions (relative risk [RR] 5.6, [95% CI 2.8–11.1], p<0.001). Findings of RCTs based on press releases were overestimated for 19 (27%) reports. News items were identified for 41 RCTs; 21 (51%) were reported with “spin,” mainly the same type of “spin” as those identified in the press release and article abstract conclusion. Findings of RCTs based on the news item was overestimated for ten (24%) reports.
Conclusion
“Spin” was identified in about half of press releases and media coverage. In multivariable analysis, the main factor associated with “spin” in press releases was the presence of “spin” in the article abstract conclusion.
Editors' Summary
Background
The mass media play an important role in disseminating the results of medical research. Every day, news items in newspapers and magazines and on the television, radio, and internet provide the general public with information about the latest clinical studies. Such news items are written by journalists and are often based on information in “press releases.” These short communications, which are posted on online databases such as EurekAlert! and sent directly to journalists, are prepared by researchers or more often by the drug companies, funding bodies, or institutions supporting the clinical research and are designed to attract favorable media attention to newly published research results. Press releases provide journalists with the information they need to develop and publish a news story, including a link to the peer-reviewed journal (a scholarly periodical containing articles that have been judged by independent experts) in which the research results appear.
Why Was This Study Done?
In an ideal world, journal articles, press releases, and news stories would all accurately reflect the results of health research. Unfortunately, the findings of randomized controlled trials (RCTs—studies that compare the outcomes of patients randomly assigned to receive alternative interventions), which are the best way to evaluate new treatments, are sometimes distorted in peer-reviewed journals by the use of “spin”—reporting that emphasizes the beneficial effects of the experimental (new) treatment. For example, a journal article may interpret nonstatistically significant differences as showing the equivalence of two treatments although such results actually indicate a lack of evidence for the superiority of either treatment. “Spin” can distort the transposition of research into clinical practice and, when reproduced in the mass media, it can give patients unrealistic expectations about new treatments. It is important, therefore, to know where “spin” occurs and to understand the effects of that “spin”. In this study, the researchers evaluate the presence of “spin” in press releases and associated media coverage and analyze whether the interpretation of RCT results based on press releases and associated news items could lead to the misinterpretation of RCT results.
What Did the Researchers Do and Find?
The researchers identified 70 press releases indexed in EurekAlert! over a 4-month period that described two-arm, parallel-group RCTs. They used Lexis Nexis, a database of news reports from around the world, to identify associated news items for 41 of these press releases and then analyzed the press releases, news items, and abstracts of the scientific articles related to each press release for “spin”. Finally, they interpreted the results of the RCTs using each source of information independently. Nearly half the press releases and article abstract conclusions contained “spin” and, importantly, “spin” in the press releases was associated with “spin” in the article abstracts. The researchers overestimated the benefits of the experimental treatment from the press release as compared to the full-text peer-reviewed article for 27% of reports. Factors that were associated with this overestimation of treatment benefits included publication in a specialized journal and having “spin” in the press release. Of the news items related to press releases, half contained “spin”, usually of the same type as identified in the press release and article abstract. Finally, the researchers overestimated the benefit of the experimental treatment from the news item as compared to the full-text peer-reviewed article in 24% of cases.
What Do These Findings Mean?
These findings show that “spin” in press releases and news reports is related to the presence of “spin” in the abstract of peer-reviewed reports of RCTs and suggest that the interpretation of RCT results based solely on press releases or media coverage could distort the interpretation of research findings in a way that favors experimental treatments. This interpretation shift is probably related to the presence of “spin” in peer-reviewed article abstracts, press releases, and news items and may be partly responsible for a mismatch between the perceived and real beneficial effects of new treatments among the general public. Overall, these findings highlight the important role that journal reviewers and editors play in disseminating research findings. These individuals, the researchers conclude, have a responsibility to ensure that the conclusions reported in the abstracts of peer-reviewed articles are appropriate and do not over-interpret the results of clinical research.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001308.
The PLOS Hub for Clinical Trials, which collects PLOS journals relating to clinical trials, includes some other articles on “spin” in clinical trial reports
EurekAlert is an online free database for science press releases
The UK National Health Service Choices website includes Beyond the Headlines, a resource that provides an unbiased and evidence-based analysis of health stories that make the news for both the public and health professionals
The US-based organization HealthNewsReview, a project supported by the Foundation for Informed Medical Decision Making, also provides expert reviews of news stories
doi:10.1371/journal.pmed.1001308
PMCID: PMC3439420  PMID: 22984354
24.  Publication trends in noninvasive cardiovascular imaging: 1991-2011: a retrospective observational study 
The last twenty years have seen an explosive growth in cardiovascular disease research. The purpose of our study was to evaluate the characteristics of published research in the field of non-invasive cardiovascular imaging research from 1991-2011. Our aims were to determine: (1) the origin of the studies (international or from the U.S.) (2) differences in funding sources for U.S. publications and (3) if there has been an evolving trend pertaining to the mode of imaging. We evaluated characteristics of original research articles from Circulation, Circulation cardiovascular imaging, Journal of the American College of Cardiology (JACC), Journal of the American College of Cardiology cardiovascular imaging, Journal of the American Medical Association and the New England Journal of Medicine for the years 1991-91, 2001-02 and 2010-11. To establish trends for contributions for U.S. based studies and proportions of U.S. based studies receiving NIH funding in the study period, data was compared using a chi-square test. A two sided p value of less than or equal to 0.05 was used as the threshold for significance. Differences in modes of imaging under study were made by comparing average number of publications between the data sets in the study period using a t-test analysis. A total of 5431 studies were reviewed; 594 studies were selected as per the standardized abstraction criteria. U.S. based publications outnumbered international publications; its’ share declined from 77% in 1991-92 to 57% in 2010-2011 (p<0.0001). Funding for U.S. publications by the National Institutes of Health (NIH) remained static (1991-92: 40%; 2001-02: 49%; 2010-11: 42%). A decline was seen in the investigation of echocardiography (47%, p=0.44); cardiac computed tomography and cardiac magnetic resonance imaging studies grew 6.5 times (p=0.002) and 7-fold (p=0.01) respectively. Nuclear cardiology imaging fell by more than 50% (p=0.02). The last twenty years have seen a globalization of research in non-invasive cardiovascular imaging with a shift in focus towards investigation of cardiac magnetic resonance imaging. The decline in U.S. based publications coupled with a stasis in NIH funding may call for increased federal support for non-invasive imaging research.
PMCID: PMC3819584  PMID: 24224136
Cardiac; imaging; cardiovascular research; National Institutes of Health; funding; diagnostic techniques; echocardiography; Doppler; MRI; computed tomography
25.  Is German Medical Education Research on the rise? An analysis of publications from the years 2004 to 2013 
Objectives: The point of departure for the present work is the observation that, in comparison with Anglo-American countries or the Netherlands, Germany was responsible for only a marginal number of international publications in the field of medical education research before 2004. Recent years, however, have seen an increase in the importance of medical education research in Germany. The objective of this article is to evaluate the extent to which this trend can be substantiated by increased German publishing activity since the year 2004 in international, English-language journals in the subject area of “medical education research”.
Methods: In the framework of a literature and content analysis, German-author articles from the years 2004 to 2013 in six international, English-language medical education research journals were evaluated. In order to obtain an overview of German research activity in this area, all project and original works with German first and last authors were identified and subjected to a more in-depth content analysis.
Results: In total, 10,055 articles were examined. The evaluation shows that between the years 2004 and 2013 179 articles (of which 145 are project or original works) by German authors were published in the journals examined. Fluctuations over the course of time were evidenced. The project and original works are primarily cross-sectional studies (27.8%) and randomised control studies (25.6%) on the subject of “teaching and learning methods” (43.6%).
Conclusions: In comparison with the years 2004-2008, a significant rise can be seen in the number of publications by German education researchers in international journals since the year 2009.
doi:10.3205/zma000972
PMCID: PMC4580754  PMID: 26413168
medical education research; literature analysis; content analysis; international publication

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