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1.  Disclosing Individual CDKN2A Research Results to Melanoma Survivors: Interest, Impact, and Demands on Researchers 
Whether to return individual research results from cancer genetics studies is widely debated, but little is known about how participants respond to results disclosure or about its time and cost burdens on investigators.
We recontacted participants at one site of a multicenter genetic epidemiologic study regarding their CDKN2A gene test results and implications for melanoma risk. Interested participants were disclosed their results by telephone and followed for 3 months.
Among 39 patients approached, 27 were successfully contacted, and 19 (70% uptake) sought results, including three with mutations. Prior to disclosure, participants endorsed numerous benefits of receiving results (mean = 7.7 of 9 posed), including gaining information relevant to their children’s disease risk. Mean psychological well-being scores did not change from baseline, and no decreases to melanoma prevention behaviors were noted. Fifty-nine percent of participants reported that disclosure made participation in future research more likely. Preparation for disclosure required 40 minutes and $611 per recontact attempt. An additional 78 minutes and $68 was needed to disclose results.
Cancer epidemiology research participants who received their individual genetic research results showed no evidence of psychological harm or false reassurance from disclosure and expressed strong trust in the accuracy of results. Burdens to our investigators were high, but protocols may differ in their demands and disclosure may increase participants’ willingness to enroll in future studies.
Providing individual study results to cancer genetics research participants poses potential challenges for investigators, but many participants desire and respond positively to this information.
PMCID: PMC3833711  PMID: 21307304
2.  When research seems like clinical care: a qualitative study of the communication of individual cancer genetic research results 
BMC Medical Ethics  2008;9:4.
Research ethicists have recently declared a new ethical imperative: that researchers should communicate the results of research to participants. For some analysts, the obligation is restricted to the communication of the general findings or conclusions of the study. However, other analysts extend the obligation to the disclosure of individual research results, especially where these results are perceived to have clinical relevance. Several scholars have advanced cogent critiques of the putative obligation to disclose individual research results. They question whether ethical goals are served by disclosure or violated by non-disclosure, and whether the communication of research results respects ethically salient differences between research practices and clinical care. Empirical data on these questions are limited. Available evidence suggests, on the one hand, growing support for disclosure, and on the other, the potential for significant harm.
This paper explores the implications of the disclosure of individual research results for the relationship between research and clinical care through analysis of research-based cancer genetic testing in Ontario, Canada in the late 1990s. We analyze a set of 30 interviews with key informants involved with research-based cancer genetic testing before the publicly funded clinical service became available in 2000.
We advance three insights: First, the communication of individual research results makes research practices seem like clinical services for our respondents. Second, while valuing the way in which research enables a form of clinical access, our respondents experience these quasi-clinical services as inadequate. Finally, our respondents recognize the ways in which their experience with these quasi-clinical services is influenced by research imperatives, but understand and interpret the significance and appropriateness of these influences in different ways.
Our findings suggest that the hybrid state created through the disclosure of research results about individuals that are perceived to be clinically relevant may produce neither sufficiently adequate clinical care nor sufficiently ethical research practices. These findings raise questions about the extent to which research can, and should, be made to serve clinical purposes, and suggest the need for further deliberation regarding any ethical obligation to communicate individual research results.
PMCID: PMC2267198  PMID: 18294373
3.  When Do HIV-Infected Women Disclose Their HIV Status to Their Male Partner and Why? A Study in a PMTCT Programme, Abidjan 
PLoS Medicine  2007;4(12):e342.
In Africa, women tested for HIV during antenatal care are counselled to share with their partner their HIV test result and to encourage partners to undertake HIV testing. We investigate, among women tested for HIV within a prevention of mother-to-child transmission of HIV (PMTCT) programme, the key moments for disclosure of their own HIV status to their partner and the impact on partner HIV testing.
Methods and Findings
Within the Ditrame Plus PMTCT project in Abidjan, 546 HIV-positive and 393 HIV-negative women were tested during pregnancy and followed-up for two years after delivery. Circumstances, frequency, and determinants of disclosure to the male partner were estimated according to HIV status. The determinants of partner HIV testing were identified according to women's HIV status. During the two-year follow-up, disclosure to the partner was reported by 96.7% of the HIV-negative women, compared to 46.2% of HIV-positive women (χ2 = 265.2, degrees of freedom [df] = 1, p < 0.001). Among HIV-infected women, privileged circumstances for disclosure were just before delivery, during early weaning (at 4 mo to prevent HIV postnatal transmission), or upon resumption of sexual activity. Formula feeding by HIV-infected women increased the probability of disclosure (adjusted odds ratio 1.54, 95% confidence interval 1.04–2.27, Wald test = 4.649, df = 1, p = 0.031), whereas household factors such as having a co-spouse or living with family reduced the probability of disclosure. The proportion of male partners tested for HIV was 23.1% among HIV-positive women and 14.8% among HIV-negative women (χ2 = 10.04, df = 1, p = 0.002). Partners of HIV-positive women who were informed of their wife's HIV status were more likely to undertake HIV testing than those not informed (37.7% versus 10.5%, χ2 = 56.36, df = 1, p < 0.001).
In PMTCT programmes, specific psychosocial counselling and support should be provided to women during the key moments of disclosure of HIV status to their partners (end of pregnancy, weaning, and resumption of sexual activity). This support could contribute to improving women's adherence to the advice given to prevent postnatal and sexual HIV transmission.
In a mother-to-child HIV prevention program in Côte d'Ivoire, Annabel Desgrées-du-Loû and colleagues identify three junctures at which women tend to disclose their HIV status to partners.
Editors' Summary
Since the first reported case of AIDS (acquired immunodeficiency syndrome) in 1981, the number of people infected with the human immunodeficiency virus (HIV), which causes AIDS, has risen steadily. By the end of 2006, nearly 40 million people were infected, 25 million of them in sub-Saharan Africa. HIV is most often spread by having unprotected sex with an infected partner. In Africa, most sexual transmission of HIV is between partners in stable relationships—many such couples do not adopt measures that prevent viral transmission, such as knowing the HIV status of both partners and using condoms if one partner is HIV-positive. HIV can also pass from a mother to her baby during pregnancy, labor, or delivery, or through breastfeeding. Mother-to-child transmission (MTCT) of HIV can be reduced by giving anti-HIV drugs to the mother during pregnancy and labor and to her newborn baby, and by avoiding breastfeeding or weaning the baby early.
Why Was This Study Done?
Many African countries have programs for prevention of MTCT (PMTCT) that offer pregnant women prenatal HIV counseling and testing. As a result, women are often the first member of a stable relationship to know their HIV status. PMTCT programs advise women to disclose their HIV test result to their partner and to encourage him to have an HIV test. But for many women, particularly those who are HIV-positive, talking to their partner about HIV/AIDS is hard because of fears of rejection (which could mean loss of housing and food) or accusations of infidelity. Knowing more about when women disclose their HIV status and what makes them decide to do so would help the people running PMTCT programs to support women during the difficult process of disclosure. In this study, the researchers have investigated when and why women participating in a PMTCT research project in Abidjan (Côte d'Ivoire) told their partner about their HIV status and the impact this disclosure had on their partner's uptake of HIV testing.
What Did the Researchers Do and Find?
At regular follow-up visits, the researchers asked women in the Abidjan PMTCT project whether they had told their partners their HIV status and whether they were breast-feeding or had resumed sexual activity. Nearly all the women who tested negative for HIV, but slightly fewer than half of the HIV-positive (infected) women had told their partner about their HIV status by two years after childbirth. Two-thirds of the HIV-positive women who disclosed their status did so before delivery. Other key times for disclosure were at early weaning (4 months after birth) for women who breast-fed their babies, and when sexual activity resumed. HIV-positive women who bottle fed their babies from birth were more likely to tell their partners of their status than women who breast-fed. Factors that prevented women disclosing their HIV status included living in a polygamous relationship or living separately from their partners. Finally, the researchers report that the partners of HIV-positive women who disclosed their HIV status were about three times more likely to take an HIV test than the partners of HIV-positive women who did not disclose.
What Do These Findings Mean?
These findings identify three key times when women who have had an HIV test during pregnancy are likely to disclose their HIV status to their partner. The main one is before delivery and relates, in part, to how the mother plans to feed her baby. To bottle feed in Abidjan, women need considerable support from their partners and this may be the impetus for disclosing their HIV status. Disclosure at early weaning may reflect the woman's need to enlist her partner's support for this unusual decision—the normal time for weaning in Abidjan is 17 months. Finally, disclosure when sexual activity resumes may be necessary so that the woman can explain why she wants to use condoms. Although these findings need confirmation in other settings, targeting counseling and support within PMTCT programs to these key moments might help HIV-positive women to tell their partners about their status. This, hopefully, would help to reduce sexual transmission of HIV within stable relationships in sub-Saharan Africa.
Additional Information.
Please access these Web sites via the online version of this summary at
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS and on HIV infection in women
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Women Children and HIV provides extensive information on prevention of mother-to-child transmission of HIV in developing countries
Information is available from Avert, an international AIDS charity, on HIV and AIDS in Africa and on HIV and AIDS prevention
AIDSinfo, a service of the US Department of Health and Human Services provideshealth information for HIV-positive pregnant women (in English and Spanish)
PMCID: PMC2100145  PMID: 18052603
4.  Psychological, behavioral and social effects of disclosing Alzheimer’s disease biomarkers to research participants: a systematic review 
Current Alzheimer’s disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants.
We performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group.
Fourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning.
In cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed.
Trial registration
PROSPERO international prospective register for systematic reviews CRD42016035388. Registered 19 February 2016.
Electronic supplementary material
The online version of this article (doi:10.1186/s13195-016-0212-z) contains supplementary material, which is available to authorized users.
PMCID: PMC5103503  PMID: 27832826
Alzheimer’s disease; Biomarkers; Disclosure; Risk; Psychological effects; Behavioral effects; Social effects; Prevention studies; Clinical research; Ethics
5.  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.
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%]).
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
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
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
PMCID: PMC3413710  PMID: 22899894
6.  Returning individual research results for genome sequences of pancreatic cancer 
Genome Medicine  2014;6(5):42.
Disclosure of individual results to participants in genomic research is a complex and contentious issue. There are many existing commentaries and opinion pieces on the topic, but little empirical data concerning actual cases describing how individual results have been returned. Thus, the real life risks and benefits of disclosing individual research results to participants are rarely if ever presented as part of this debate.
The Australian Pancreatic Cancer Genome Initiative (APGI) is an Australian contribution to the International Cancer Genome Consortium (ICGC), that involves prospective sequencing of tumor and normal genomes of study participants with pancreatic cancer in Australia. We present three examples that illustrate different facets of how research results may arise, and how they may be returned to individuals within an ethically defensible and clinically practical framework. This framework includes the necessary elements identified by others including consent, determination of the significance of results and which to return, delineation of the responsibility for communication and the clinical pathway for managing the consequences of returning results.
Of 285 recruited patients, we returned results to a total of 25 with no adverse events to date. These included four that were classified as medically actionable, nine as clinically significant and eight that were returned at the request of the treating clinician. Case studies presented depict instances where research results impacted on cancer susceptibility, current treatment and diagnosis, and illustrate key practical challenges of developing an effective framework.
We suggest that return of individual results is both feasible and ethically defensible but only within the context of a robust framework that involves a close relationship between researchers and clinicians.
PMCID: PMC4067993  PMID: 24963353
7.  Attitudes of Research Participants and the General Public Regarding Disclosure of Alzheimer Disease Research Results 
JAMA neurology  2015;72(12):1484-1490.
Results of Alzheimer disease (AD) research assessments typically are not disclosed to participants. Recent research has suggested interest in disclosure, but, to our knowledge, few studies have accounted for awareness of potential benefits and limitations of disclosure.
To determine the attitudes of cognitively normal research participants and members of the general public regarding disclosure of AD research results.
Participants in a longitudinal aging study (Alzheimer Disease Research Center [ADRC]) were given preintervention and postintervention surveys about disclosure attitudes. In a general public sample (The American Panel Survey), participants responded to a similar survey about disclosure attitudes.
Participants in the ADRC sample were randomly assigned to a group (n = 119) that read an education intervention about the usefulness of AD biomarkers or to a placebo group (n = 100) that read as its intervention general information about the ADRC. Participants in the general public sample read a brief vignette describing participation in a longitudinal AD study.
Interest in disclosure of AD research results.
Cognitively normal ADRC participants (n = 219) were 60.7% (n = 133) female, 83.6% (n = 183) of white race, and reported a mean of 15.91 years of education. Twenty-nine individuals refused participation. The American Panel Survey participants (n = 1418) indicated they did not have AD and were 50.5% (n = 716) female, 76.7% (n = 1087) of white race, and reported a mean of 13.85 years of education. Overall, 77.6% of eligible participants (1583 of 2041) completed the survey in July 2014. Interest in disclosure was high among the ADRC participants (55.1% [119 of 216] were “extremely interested”). Viewing the education intervention predicted lower interest in disclosure (odds ratio, 2.01; 95% CI, 1.15–3.53; P = .02). High subjective risk of AD, a family history of AD, and minimal attendance at research meetings were associated with high interest after the intervention. In the general public, interest was lower overall (12.5% [174 of 1389] were “extremely interested”), but the subset of participants most likely to join an AD research study reported higher interest (43.5% [40 of 92] were extremely interested).
Experience with AD appears to increase interest in disclosure of AD research results. Learning about potential limitations of disclosure somewhat tempered interest. These findings should inform the development of disclosure policies for asymptomatic individuals in AD studies.
PMCID: PMC4694568  PMID: 26501506
8.  Development of a process to disclose amyloid imaging results to cognitively normal older adult research participants 
The objective of this study was to develop a process to maximize the safety and effectiveness of disclosing Positron Emission Tomography (PET) amyloid imaging results to cognitively normal older adults participating in Alzheimer’s disease secondary prevention studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Study.
Using a modified Delphi Method to develop consensus on best practices, we gathered and analyzed data over three rounds from experts in two relevant fields: informed consent for genetic testing or human amyloid imaging.
Experts reached consensus on (1) text for a brochure that describes amyloid imaging to a person who is considering whether to undergo such imaging in the context of a clinical trial, and (2) a process for amyloid PET result disclosure within such trials. Recommendations included: During consent, potential participants should complete an educational session, where they receive verbal and written information covering what is known and unknown about amyloid imaging, including possible results and their meaning, implications of results for risk of future cognitive decline, and information about Alzheimer’s and risk factors. Participants should be screened for anxiety and depression to determine suitability to receive amyloid imaging information. The person conducting the sessions should check comprehension and be skilled in communication and recognizing distress. Imaging should occur on a separate day from consent, and disclosure on a separate day from imaging. Disclosure should occur in person, with time for questions. At disclosure, investigators should assess mood and willingness to receive results, and provide a written results report. Telephone follow-up within a few days should assess the impact of disclosure, and periodic scheduled assessments of depression and anxiety, with additional monitoring and follow-up for participants showing distress, should be performed.
We developed a document for use with potential study participants to describe the process of amyloid imaging and the implications of amyloid imaging results; and a disclosure process with attention to ongoing monitoring of both mood and safety to receive this information. This document and process will be used in the A4 Study and can be adapted for other research settings.
PMCID: PMC4428104  PMID: 25969699
9.  Offering Individual Genetic Research Results: Context Matters 
Science translational medicine  2010;2(38):38cm20.
The disclosure of individual genetic research results to participants continues to be the subject of vigorous debate, centered primarily on the nature of the results: What are the criteria for the kinds of information that should, could, or should not be offered? There are widely diverging views about how to define these categories, as reasonable people can disagree about the value of various kinds of information. Data concerning participant preferences regarding receipt of results are important, but not determinative of researchers’ fundamental obligations.
We suggest that research context is a vital consideration that has not been sufficiently incorporated into the discussion. We adapt an ancillary care framework to explore what different contexts might call for with regard to offering individual genetic research results. Our analysis suggests that, beyond exceptionally rare circumstances that give rise to a duty to rescue, a “one size fits all” threshold cannot be developed for decisions about return of individual results. Instead, researchers and IRBs must consider the scope of entrustment involved in the research, the intensity and duration of interactions with participants, and the vulnerability and dependence of the study population. The strength of this approach is that research context is foreseeable at the time a study is designed. Assessments of the nature and value of the information may still be required to decide whether to offer a particular result, but perhaps will be facilitated by a more grounded understanding of researchers’ obligations in different contexts.
PMCID: PMC3136874  PMID: 20592417
10.  Communication of Genetic Test Results to Family and Health Care Providers Following Disclosure of Research Results 
Few studies have examined methods to promote communication following the return of DNA mismatch repair (MMR) genetic test results obtained during research. The purpose of the present study was to evaluate a telephone protocol for returning research results of MMR gene testing to identify Lynch Syndrome.
We invited individuals with known MMR mutations in their family who were enrolled in the Colon Cancer Family Registry at the Mayo Clinic to participate. Participants completed surveys before and 6-months after MMR test result disclosure.
Among 107 participants, 79% opted to learn their MMR test results; of these, 44 (41%) carried MMR mutations. Post-disclosure, 54% reported screening for any type of cancer. Among carriers, >74% reported communicating results to family; communication was predicted by baseline confidence in coping with the genetic test result (Z=1.97, P=.04). Result disclosure to a physician was predicted by greater perceived cancer risk (Z=2.08, P=.03) and greater intention to share results with family (Z=3.07, P=.002).
Research vs. clinically-based gene disclosure presents challenges. A telephone disclosure process for the return of research-based results among Lynch syndrome families led to high rates of result uptake and participant communication of results to providers and family members.
PMCID: PMC4009372  PMID: 24091800
gene test disclosure; research; telephone genetic education; communication; Lynch Syndrome
11.  Disclosure of Genetic Research Results to Members of a Founder Population 
Journal of genetic counseling  2014;23(6):984-991.
There is currently extensive discussion and debate in the literature on how, when, and to whom genetic research results should be returned (see Genetics in Medicine, April 2012 issue). Here, we describe our experience in disclosing genetic information on Mendelian disorders discovered during the course of our research in the Hutterites. We first assessed attitudes toward the disclosure of carrier results, which revealed that many individuals wanted carrier information and that many intended to use the information in family planning. Based on this information, we developed a pilot study to test and disclose cystic fibrosis (CF) carrier status. Next, a larger scale project was developed in order to disclose genetic research results for 14 diseases to those interested in receiving the information. We developed brochures, offered a live interactive educational program, conducted a consent process, and disclosed results in letters mailed to the consented individuals. Overall, ∼80% of individuals who participated in the educational program signed consent forms for the release of their results for 14 diseases. We describe our experience with returning individual genetic research results to participants in a population-based research study.
PMCID: PMC4337808  PMID: 24777552
disclosure; genetic; results; research; individual; Hutterite
12.  What is a meaningful result? Disclosing the results of genomic research in autism to research participants 
Developments in genomics research have been accompanied by a controversial ethical injunction: that researchers disclose individually relevant research results to research participants. With the explosion of genomic research on complex psychiatric conditions such as autism, researchers must increasingly contend with whether – and which results – to report. We conducted a qualitative study with researchers and participants involved in autism genomics research, including 4 focus groups and 23 interviews with parents of autistic children, and 23 interviews with researchers. Respondents considered genomic research results ‘reportable' when results were perceived to explain cause, and answer the question ‘why;' that is, respondents set a standard for reporting individually relevant genetic research results to individual participants that is specific to autism, reflecting the metaphysical value that genetic information is seen to offer in this context. In addition to this standard of meaning, respondents required that results be deemed ‘true.' Here, respondents referenced standards of validity that were context nonspecific. Yet in practice, what qualified as ‘true' depended on evidentiary standards within specific research disciplines as well as fundamental, and contested, theories about how autism is ‘genetic.' For research ethics, these finding suggest that uniform and context-free obligations regarding result disclosure cannot readily be specified. For researchers, they suggest that result disclosure to individuals should be justified not only by perceived meaning but also by clarity regarding appropriate evidentiary standards, and attention to the status of epistemological debates regarding the nature and cause of disorders.
PMCID: PMC2987386  PMID: 20234389
research ethics; duty to disclose; genomics; research results; autism; psychiatric genetics
13.  Comparing test-specific distress of susceptibility versus deterministic genetic testing for Alzheimer’s disease 
Genetic risk for Alzheimer’s disease (AD) may be conferred by the susceptibility polymorphism apolipoprotein E (APOE), where the ε4 allele increases the risk of developing late-onset Alzheimer’s disease but is not a definitive predictor of the disease, or by autosomal dominant mutations (e.g., the presenilins), which almost inevitably result in early-onset familial Alzheimer’s disease. The purpose of this study was to compare the psychological impact of using these two different types of genetic information to disclose genetic risk for AD to family members of affected patients.
Data were compared from two separate protocols. The Risk Evaluation and Education for Alzheimer’s Disease (REVEAL) Study is a randomized, multi-site clinical trial that evaluated the impact of susceptibility testing for Alzheimer’s disease with APOE in 101 adult children of Alzheimer’s disease patients. A separate study, conducted at the University of Washington, assessed the impact of deterministic genetic testing by disclosing presenilin-1, presenilin-2, or TAU genotype to 22 individuals at risk for familial Alzheimer’s disease or frontotemporal dementia. In both protocols, participants received genetic counseling and completed the Impact of Event Scale (IES), a measure of test-specific distress. Scores were analyzed at the time point closest to one year post-disclosure at which IES data were available. The role of genetic test result (positive vs. negative) and type of genetic testing (deterministic vs. susceptibility) in predicting log-transformed IES scores was assessed with linear regression, controlling for age, gender, and time from disclosure.
Subjects from the REVEAL Study who learned that they were positive for the susceptibility gene APOE ε4+ experienced similar, low levels of test-specific distress compared to those who received positive results of deterministic testing in the University of Washington study (p= 0.78). APOE ε4+ individuals in the susceptibility protocol experienced more test-specific distress than those who tested ε4− in the same study (p= 0.04); however, among those receiving deterministic test disclosure, the subjects who received positive results did not experience significantly higher levels of distress when compared to those who received negative results (p= 0.88).
The findings of this preliminary study, with limited sample size, suggest that the test-related distress experienced by those receiving positive results for a deterministic mutation is similar to the distress experienced by those receiving positive results from genetic susceptibility testing, and that the majority of participants receiving genotype disclosure do not experience clinically significant distress as indicated by IES scores one year after learning of their test results.
PMCID: PMC2610442  PMID: 19012865
genetic susceptibility testing; deterministic testing; Alzheimer’s disease; APOE; genetic counseling
14.  Development of a Standardized Approach to Disclosing Amyloid Imaging Research Results in Mild Cognitive Impairment 
The increased use of PET amyloid imaging in clinical research has sparked numerous concerns about whether and how to return such research test results to study participants. Chief among these is the question of how best to disclose amyloid imaging research results to individuals who have cognitive symptoms that could impede comprehension of the information conveyed. We systematically developed and evaluated informational materials for use in pre-test counseling and post-test disclosures of amyloid imaging research results in mild cognitive impairment (MCI). Using simulated sessions, persons with MCI and their family care partners (N=10 dyads) received fictitious but realistic information regarding brain amyloid status, followed by an explanation of how results impact Alzheimer’s disease risk. Satisfaction surveys, comprehension assessments, and focus group data were analyzed to evaluate the materials developed. The majority of persons with MCI and their care partners comprehended and were highly satisfied with the information presented. Focus group data reinforced findings of high satisfaction and included 6 recommendations for practice: 1) offer pre-test counseling, 2) use clear graphics, 3) review participants’ own brain images during disclosures, 4) offer take-home materials, 5) call participants post-disclosure to address emerging questions, and 6) communicate seamlessly with primary care providers. Further analysis of focus group data revealed that participants understood the limitations of amyloid imaging, but nevertheless viewed the prospect of learning one’s amyloid status as valuable and empowering.
PMCID: PMC4860948  PMID: 27060950
15.  Disclosure of Individualized Research Results: A Precautionary Approach 
Accountability in research  2011;18(6):382-397.
Assessing and managing risks to participants is a central point of contention in the debate about disclosing individualized research results. Those who favor disclosure of only clinically significant results think that disclosing clinically insignificant results is risky and costly, and that harm prevention should take precedence over other ethical considerations. Those who favor giving participants the option of full disclosure regard these risks as insubstantial, and think that obligations to benefit participants and promote their autonomy and right to know outweigh the obligation to prevent harm or financial considerations. The risks of disclosing clinically insignificant research results are currently not quantifiable, due to lack of empirical data. The precautionary principle provides some insight into this debate because it applies to decision-making concerning risks that are plausible but not quantifiable. A precautionary approach would favor full disclosure of individualized results with appropriate safeguards to prevent, minimize, or mitigate risks to participants, such as: validating testing methods; informing participants about their options for receiving tests results and the potential benefits and risks related to receiving results; assessing participants' comfort with handling uncertainty; providing counseling and advice to participants; following-up with individuals who receive tests results; and forming community advisory boards to help investigators deal with issues related to disclosure.
PMCID: PMC3953618  PMID: 22011068
autonomy; beneficence; disclosing research results; precautionary principle; risk
16.  HIV serostatus disclosure among people living with HIV/AIDS in Mwanza, Tanzania 
Disclosing HIV serostatus is important for HIV prevention and maintenance of health for people living with HIV their spouses and the community, it plays a role in the social relation which is critical in reducing HIV transmission. The process may have positive and negative effects to the HIV infected people who disclose their status. The present study was undertaken to describe HIV serostatus disclosure among HIV infected people attending care and treatment clinic at Sekou-Toure hospital in Mwanza, Tanzania.
A cross-sectional study was carried out on 270 HIV infected adults attending Care and Treatment Clinic (CTC) at Sekou-Toure hospital between September and October, 2010. A Swahili questionnaire was used to obtain demographic and HIV disclosure information.
Hundred and ninety five (72.5%) of all recruited participants were females, 88.1% (238/270) were aged above 30 years and 44.1% (119/270) were married. The prevalence of serostatus disclosure was 93.3% (252/270) with participants aged above 30 years having significantly higher proportion of serostatus disclosure compared to those aged below 30 years (94.5% vs. 84.4%, p < 0.05). Among the participants who disclosed their status, 69.3% reported closeness to the disclosed person as the reason for disclosure while 25.8% (65/252) disclosed because they needed help. Two hundred (79.4%) reported to have received emotional support following disclosure while 25.8% and 29.7% received financial support and freedom to use their anti-retroviral drugs around the person they disclosed their status respectively. Thirty four participants reported to have been discriminated following disclosure and 12 participants reported to have been divorced.
Rate of disclosure of HIV serostatus was noted to be high in this study. Delayed disclosure was also noted in small proportion of participants. Negative outcomes following disclosure of serostatus were reported by participants. Efforts need to be increased to promote disclosure of HIV serostatus in Tanzania through health education and awareness for both HIV infected individuals and the community.
PMCID: PMC3900936  PMID: 24450933
17.  Acknowledging awareness: informing families of individual research results for patients in the vegetative state 
Journal of Medical Ethics  2014;41(7):534-538.
Recent findings in cognitive neuroscience have revealed that some patients previously diagnosed as being in a vegetative state may retain some degree of covert awareness. However, it is unclear whether such findings should be disclosed to the families of these patients. Concerns about the preservation of scientific validity, reliability of results and potential harms associated with disclosure suggest that individual research results should be disclosed only under certain conditions. In the following paper, we offer four criteria for the disclosure of individual research results. Because the results of functional neuroimaging studies to detect covert awareness in vegetative patients are scientifically valid, informative and reasonably reliable and have considerable potential benefit for the patient, researchers have an obligation to disclose such results to family members. Further work is needed to develop educational materials for families and to systematically study the impact of disclosure on the families themselves.
PMCID: PMC4515978  PMID: 25079068
Research Ethics; Neuroimaging; Neuroethics; Informed Consent; Consciousness
18.  Using AD biomarker research results for clinical care 
Neurology  2013;81(13):1114-1121.
To inform whether the Alzheimer's Disease Neuroimaging Initiative (ADNI) should change its policy of not returning research results to ADNI participants, we surveyed investigators and research staff about disclosing ADNI biomarker information to research participants, with particular emphasis on amyloid imaging results.
In April 2012, just before Food and Drug Administration approval of the amyloid-binding radiotracer, florbetapir, all ADNI investigators and personnel were recruited to complete an anonymous online survey that contained fixed choice and free-text questions.
Although ADNI participants often requested amyloid imaging results (the proportions of investigators who reported requests from more than half of their participants with normal cognition or mild cognitive impairment were 20% and 22%, respectively), across all diagnostic groups, the majority of ADNI investigators (approximately 90%) did not return amyloid imaging results to ADNI participants. However, the majority of investigators reported that, if the Food and Drug Administration approved florbetapir, they would support the return of amyloid imaging results to participants with mild cognitive impairment and normal cognition, but they emphasized the need for guidance on how to provide these results to participants and for research to assess the value of returning results as well as how returning results will affect study validity and participant well-being.
A majority of ADNI investigators support returning amyloid imaging results to ADNI participants. The findings that they want guidance on how to do this and research on the impact of disclosure suggest how to develop and monitor a disclosure process.
PMCID: PMC3795601  PMID: 23966249
19.  Physician self-disclosure in primary care: a mixed methods study of GPs’ attitudes, skills, and behaviour 
The British Journal of General Practice  2015;65(638):e601-e608.
There is a debate in medicine about the use and value of self-disclosure by the physician as a communication tool. There is little empirical evidence about GPs and self-disclosure.
To explore what GPs’ attitudes, skills, and behaviour are with regard to self-disclosure during a clinical consultation and whether there is a need for the development of training resources.
Design and setting
Mixed methods using open-ended and semi-structured interviews in Auckland, New Zealand, and the surrounding districts.
Sixteen GPs were interviewed on the issue of self-disclosure in clinical practice. A general inductive approach was used for data analysis.
Self-disclosure was common in this group of GPs, contrary to training in some of the groups, and was seen as a potentially positive activity. Family and physical topics were most common, yet psychological and relationship issues were also discussed. Knowing patients made self-disclosure more likely, but a GP’s intuition played the main role in determining when to self-disclose, and to whom. GPs have developed their own guidelines, shaped by years of experience; however, there was a consensus that training would be helpful.
Self-disclosure is common and, in general, seen as positive. Major personal issues were acceptable for some GPs to self-disclose, especially to known patients. Although participants had developed their own guidelines, exposure of trainees to the issue of self-disclosure would be of value to prevent future mistakes and to protect both doctor and patient from any unintended harm, for example, developing a dependent relationship.
PMCID: PMC4540400  PMID: 26324497
education; general practice; physician–patient relations; self disclosure
20.  Disclosing clinical adverse events to patients: can practice inform policy? 
Objectives  To understand patients’ and health professionals’ experience of Open Disclosure and how practice can inform policy.
Background  Open Disclosure procedures are being implemented in health services worldwide yet empirical evidence on which to base models of patient–clinician communication and policy development is scant.
Design, setting and participants  A qualitative method was employed using semi‐structured open‐ended interviews with 154 respondents (20 nursing, 49 medical, 59 clinical/administrative managerial, 3 policy coordinators, 15 patients and 8 family members) in 21 hospitals and health services in four Australian states.
Results  Both patients and health professionals were positive about Open Disclosure, although each differed in their assessments of practice effectiveness. We found that five major elements influenced patients’ and professionals’ experience of openly disclosing adverse events namely: initiating the disclosure, apologizing for the adverse event, taking the patient’s perspective, communicating the adverse event and being culturally aware.
Conclusions  Evaluating the impact of Open Disclosure refines policy implementation because it provides an evidence base to inform policy. Health services can use specific properties relating to each of the five Open Disclosure elements identified in this study as training standards and to assess the progress of policy implementation. However, health services must surmount their sensitivity to revealing the extent of error so that research into patient experiences can inform practice and policy development.
PMCID: PMC5060526  PMID: 19804555
evaluation; medical error; Open Disclosure; patient involvement; policy implementation
21.  A Randomized Non-inferiority Trial of Condensed Protocols for Genetic Risk Disclosure of Alzheimer’s Disease 
Conventional multi-session genetic counseling is currently recommended when disclosing APOE genotype for risk of Alzheimer’s disease (AD) in cognitively normal individuals.
To evaluate the safety of brief disclosure protocols for disclosing APOE genotype for risk of Alzheimer’s disease (AD).
A randomized, multicenter non-inferiority trial was conducted at 4 sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared to condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Pre-planned co-primary outcomes were anxiety and depression scales 12 months after disclosure.
343 adults (mean age 58.3, range 33–86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n= 115), CP-GC protocol (n=116) or CP-MD protocol (n=112). Mean post-disclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC to SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all p<0.001 on non-inferiority tests), establishing non-inferiority for condensed protocols. Results were similar between European Americans and African Americans.
These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.
PMCID: PMC4461546  PMID: 25499536
Alzheimer; APOE; genetics; genomics; risk assessment; personalized medicine
22.  Disclosing intimate partner violence to health care clinicians - What a difference the setting makes: A qualitative study 
BMC Public Health  2008;8:229.
Despite endorsement by national organizations, the impact of screening for intimate partner violence (IPV) is understudied, particularly as it occurs in different clinical settings. We analyzed interviews of IPV survivors to understand the risks and benefits of disclosing IPV to clinicians across specialties.
Participants were English-speaking female IPV survivors recruited through IPV programs in Massachusetts. In-depth interviews describing medical encounters related to abuse were analyzed for common themes using Grounded Theory qualitative research methods. Encounters with health care clinicians were categorized by outcome (IPV disclosure by patient, discovery evidenced by discussion of IPV by clinician without patient disclosure, or non-disclosure), attribute (beneficial, unhelpful, harmful), and specialty (emergency department (ED), primary care (PC), obstetrics/gynecology (OB/GYN)).
Of 27 participants aged 18–56, 5 were white, 10 Latina, and 12 black. Of 59 relevant health care encounters, 23 were in ED, 17 in OB/GYN, and 19 in PC. Seven of 9 ED disclosures were characterized as unhelpful; the majority of disclosures in PC and OB/GYN were characterized as beneficial. There were no harmful disclosures in any setting. Unhelpful disclosures resulted in emotional distress and alienation from health care. Regardless of whether disclosure occurred, beneficial encounters were characterized by familiarity with the clinician, acknowledgement of the abuse, respect and relevant referrals.
While no harms resulted from IPV disclosure, survivor satisfaction with disclosure is shaped by the setting of the encounter. Clinicians should aim to build a therapeutic relationship with IPV survivors that empowers and educates patients and does not demand disclosure.
PMCID: PMC2474863  PMID: 18601725
23.  The role of disclosure in relation to assent to participate in HIV-related research among HIV-infected youth: a formative study 
The objective of this study was to develop a culturally appropriate approach for obtaining assent from children aged eight to 17 years to participate in paediatric HIV-related operational research in Kinshasa, Democratic Republic of Congo (DRC). Included within this objective was to determine whether or not HIV disclosure should be included as part of the assent process prior to research participation, a component of research participation, or not incorporated in any aspect of the child's involvement in the research. Factors that influence parents' and caregivers' decisions to disclose HIV status to children in non-research contexts were also explored.
A qualitative formative study was conducted. Semi-structured interviews were conducted with 19 youth living with HIV, 36 parents and caregivers of youth living with HIV, and 17 health professionals who provide care and support to youth living with HIV and their families. Participants were purposefully selected from three HIV care, treatment and/or psychosocial support programmes in Kinshasa, DRC.
Most youth interviewed believed minors participating in HIV-related research should be informed of their HIV-positive status. Parents and caregivers and health professionals had varied perspectives on if and when HIV status should be disclosed to minors during research participation. The age of the youth influenced parents and caregivers' responses, and disclosure to adolescents was more frequently supported than disclosure to children.
Several parents and caregivers, as well as some health professionals, suggested that minors should never be told their HIV-positive status when participating in HIV-related research, regardless of their age. Within the context of treatment programmes, disclosure of HIV status to minors was supported by youth, parents and caregivers, and health professionals as a means to improve adherence to medication.
In settings where most minors are unaware of their HIV infection, researchers should consider excluding the term, "HIV", when explaining HIV-related research to minors, and omitting it from assent forms or informational sheets related to research participation. However, an individualized disclosure plan should be initiated with parents and caregivers at the time of enrolment in HIV-related research, particularly in research that involves treatment.
PMCID: PMC2753623  PMID: 19712468
Integrative cancer therapies  2008;7(3):122-129.
Physician awareness of their patients’ use of complementary and alternative medicine (CAM) is crucial, particularly in the setting of a potentially life-threatening disease such as cancer. The potential for harmful treatment interactions may be greatest when a patient sees a CAM practitioner – perceived as a physician-like authority figure – but does not disclose this to their physician. We therefore investigated the extent of nondisclosure in a large cohort of cancer patients.
We investigated CAM use in participants of the UCSD Women’s Healthy Eating and Living (WHEL) Study, a multicenter study of the effect of diet and lifestyle on disease-free and overall survival in women ages 18–70 who had completed treatment for invasive breast cancer between 1995 and 2000. Data regarding CAM use and disclosure was collected via a telephone-administered questionnaire in 2003–2004. This questionnaire asked about different CAM modalities including those requiring a “skilled CAM practitioner” (acupuncturist, chiropractor, homeopath, or naturopath) for administration. Demographic data was obtained at the WHEL baseline clinic interview. Modality-specific disclosure rates were determined and a comparison of demographic variables of disclosers versus nondisclosers was conducted using Chi-squared tests for categorical variables, and t-tests for continuous variables.
Of 3088 total WHEL participants, 2527 completed the CAM questionnaire. Of these, 2017 reported using some form of CAM. Of these, 300 received treatment from an acupuncturist, chiropractor, homeopath, or naturopath and also provided information on whether or not they disclosed this care to their conventional physician. The highest disclosure rate was for naturopathy (85%), followed by homeopathy (74%), acupuncture (71%), and chiropractic (47%). Among demographic characteristics, only education (p = 0.047) and study site (p=0.039) were associated with disclosure. College graduates and postgraduates, in particular, were more likely to disclose CAM use to their physicians than those with lesser education.
Overall, we observed moderately high rates of physician disclosure of CAM use for all modalities except chiropractic. Education and study site associations suggest that disclosure may be greater when CAM use is more prevalent and possibly more socially accepted. These findings underscore the importance of open, destigmatized patient-physician communication regarding CAM use.
PMCID: PMC2763208  PMID: 18956493
Breast cancer; CAM; complementary and alternative medicine; acupuncture; naturopathy; chiropractic; health communication; disclosure
25.  Disclosure of HIV status to children in resource-limited settings: a systematic review 
Informing children of their own HIV status is an important aspect of long-term disease management, yet there is little evidence of how and when this type of disclosure takes place in resource-limited settings and its impact.
MEDLINE, EMBASE and Cochrane Databases were searched for the terms hiv AND disclos* AND (child* OR adolesc*). We reviewed 934 article citations and the references of relevant articles to find articles describing disclosure to children and adolescents in resource-limited settings. Data were extracted regarding prevalence of disclosure, factors influencing disclosure, process of disclosure and impact of disclosure on children and caregivers.
Thirty-two articles met the inclusion criteria, with 16 reporting prevalence of disclosure. Of these 16 studies, proportions of disclosed children ranged from 0 to 69.2%. Important factors influencing disclosure included the child's age and perceived ability to understand the meaning of HIV infection and factors related to caregivers, such as education level, openness about their own HIV status and beliefs about children's capacities. Common barriers to disclosure were fear that the child would disclose HIV status to others, fear of stigma and concerns for children's emotional or physical health. Disclosure was mostly led by caregivers and conceptualized as a one-time event, while others described it as a gradual process. Few studies measured the impact of disclosure on children. Findings suggested adherence to antiretroviral therapy (ART) improved post-disclosure but the emotional and psychological effects of disclosure were variable.
Most studies show that a minority of HIV-infected children in resource-limited settings know his/her HIV status. While caregivers identify many factors that influence disclosure, studies suggest both positive and negative effects for children. More research is needed to implement age- and culture-appropriate disclosure in resource-limited settings.
PMCID: PMC3665848  PMID: 23714198
HIV; disclosure; children; resource-limited settings; systematic review

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