Evidence-based medicine promotes and relies on the use of evidence in developing clinical practice guidelines (CPGs). The Chinese healthcare system includes both traditional Chinese medicine (TCM) and Western medicine, which are expected to be equally reflected in Chinese CPGs.
To evaluate the inclusion of TCM-related information in Western medicine CPGs developed in China and the adoption of high level evidence.
All CPGs were identified from the China Guideline Clearinghouse (CGC), which is the main Chinese organisation maintaining the guidelines issued by the Ministry of Health of China, the Chinese Medical Association and the Chinese Medical Doctors’ Association.
TCM-related contents were extracted from all the CPGs identified. Extracted information comprised the institution issuing the guideline, date of issue, disease, recommendations relating to TCM, evidence level of the recommended content and references supporting the recommendations.
A total of 604 CPGs were identified, only a small number of which (74/604; 12%) recommended TCM therapy and only five guidelines (7%) had applied evidence grading. The 74 CPGs involved 13 disease systems according to the International Classification of Diseases 10th edition. TCM was mainly recommended in the treatment part of the guidelines (73/74, 99%), and more than half of the recommendations (43/74, 58%) were related to Chinese herbal medicine (single herbs or herbal treatment based on syndrome differentiation).
Few Chinese Western medicine CPGs recommend TCM therapies and very few provide evidence grading for the TCM recommendation. We suggest that future guideline development should be based on systematic searches for evidence to support CPG recommendations and involve a multidisciplinary approach including TCM expertise.
COMPLEMENTARY MEDICINE; TRANSPLANT MEDICINE; GENERAL MEDICINE (see Internal Medicine)
To quantitatively determine the prevalence of anxiety and depression in men on active surveillance (AS).
Cross-sectional questionnaire survey.
Secondary care prostate cancer (PCa) clinics across South, Central and Western England.
313 men from a total sample of 426 with a histological diagnosis of PCa currently managed with AS were identified from seven UK urology departments. The mean age of respondents was 70 (51–86) years with the majority (76%) being married or in civil partnerships. 94% of responders were of white British ethnicity.
Primary outcome measures
The prevalence of clinically meaningful depression and anxiety as assessed by the Hospital Anxiety and Depression Scale (HADS; score ≥8/21).
Secondary outcome measures
Patient demographic data (age, employment, relationship, ethnic and educational status). Each demographic variable was cross-tabulated against patients identified as depressed or anxious to allow for the identification of variables that were significantly associated with depression and anxiety. In order to determine predictors for depression and anxiety among the demographic variables, logistic regression analyses were conducted, with p<0.05 considered as indicating statistical significance.
The prevalence of clinical anxiety and depression as determined via the HADS (HADS ≥8) was 23% (n=73) and 12.5% (n=39), respectively. Published data from men in the general population of similar age has shown prevalence rates of 8% and 6%, respectively, indicating a twofold increase in depression and a threefold increase in anxiety among AS patients. Our findings also suggest that AS patients experience substantially greater levels of anxiety than patients with PCa treated radically. The only demographic predictor for anxiety or depression was divorce.
Patients with PCa managed with AS experienced substantially higher rates of anxiety and depression than that expected in the general population. Strategies to address this are needed to improve the management of this population and their quality of life.
The impact of living with metastatic breast cancer (MBC) is considerable and psychosocial support can be beneficial. Mindfulness-based stress reduction (MBSR) can help self-management of anxiety, depression, quality of life (QoL), and fatigue and has been evaluated in early-stage breast cancer but not MBC. This study investigated the acceptability and feasibility of providing MBSR for women with MBC and of introducing MBSR into a National Health Service (NHS) setting. A mixed methods convergent design was used. Eligible women with MBC, an Eastern Cooperative Oncology Group (ECOG) score of 0 to 2, stable disease, and life expectancy of at least 6 months were invited to attend (by their oncologist) an 8-week MBSR course. Qualitative interviews with patients, a focus group, and interview with NHS staff were held to explore acceptability and feasibility of MBSR. Questionnaires at baseline, during (weeks 4, 8), and after (weeks 16, 24) the course measured fatigue, anxiety and depression, mindfulness, disease-specific QoL, and generic preference based QoL. Of 100 women approached, 20 joined the study. One woman dropped out prior to the intervention due to illness progression. Nineteen women took part in 3 MBSR courses. Recruitment to 2 of the 3 courses was slow. Commitment to 8 weeks was a reason for non-participation, and proved challenging to participants during the course. Participants found the course acceptable and reported many cumulative and ongoing benefits. These included feeling less reactive to emotional distress and more accepting of the disruption to life that occurs with living with MBC. There was high attendance, completion of course sessions, adherence to home practice, excellent follow-up rates, and high questionnaire return rates. MBSR was acceptable to MBC patients, who perceived benefits such as improved anxiety and QoL; but the MBSR course requires a considerable time commitment. There is scope to tailor the intervention so that it is less intensive.
feasibility; mixed methods; metastatic breast cancer; mindfulness-based stress reduction; psychosocial support
Chinese proprietary herbal medicines (CPHMs) have long history in China for the treatment of common cold, and lots of them have been listed in the ‘China national essential drug list’ by the Chinese Ministry of Health. The aim of this review is to provide a well-round clinical evidence assessment on the potential benefits and harms of CPHMs for common cold based on a systematic literature search to justify their clinical use and recommendation.
We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites from their inception to 31 March 2013 for clinical studies of CPHMs listed in the ‘China national essential drug list’ for common cold. There was no restriction on study design.
A total of 33 CPHMs were listed in ‘China national essential drug list 2012’ for the treatment of common cold but only 7 had supportive clinical evidences. A total of 6 randomised controlled trials (RCTs) and 7 case series (CSs) were included; no other study design was identified. All studies were conducted in China and published in Chinese between 1995 and 2012. All included studies had poor study design and methodological quality, and were graded as very low quality.
The use of CPHMs for common cold is not supported by robust evidence. Further rigorous well designed placebo-controlled, randomized trials are needed to substantiate the clinical claims made for CPHMs.
Recurrent urinary tract infections (RUTIs) are commonly presented by women in primary care. In order to explore the poorly described experience of women with RUTIs a qualitative study was conducted that analysed data from a publically accessible internet-based self-help forum.
Qualitative Description was used to analyse the text with an emphasis on using the naturalistic language of the informants to portray their perceptions and experiences of RUTIs. Individual codes were identified inductively and grouped according to common ideas into related categories, before being incorporated into five main themes.
Women of diverse ages and geographical location contributed to the website. Themes were identified that vividly explored the atypical symptomatology of RUTIs, the serious impact it had on many aspects of women’s lives, different attitudes to treatments options such as antibiotics, the use of unorthodox approaches such as complementary and alternative medicines (CAM) and contrasting experiences of medical practitioners.
A web-based analysis can vividly capture the views of a diverse population. RUTIs can have a disabling effect on women’s health, their intimate and social relationships, self-esteem, and capacity for work. Further research is required to clarify the wider relevance of the qualitative themes identified, to identify key elements of good practice, and to provide a more rigorous assessment of CAM interventions.
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), in its most severe clinical presentation, can result in patients becoming housebound and bedbound so unable to access most available specialist services. This presents particular clinical risks and treatment needs for which the National Institute for Health and Care Excellence (NICE) advises specialist medical care and monitoring. The extent of National Health Service (NHS) specialist provision in England for severe CFS/ME is currently unknown.
To establish the current NHS provision for patients with severe CFS/ME in England.
Setting and participants
All 49 English NHS specialist CFS/ME adult services in England, in 2013.
Cross-sectional survey by email questionnaire.
Primary outcome measures
Adherence to NICE guidelines for severe CFS/ME.
All 49 services replied (100%). 33% (16/49) of specialist CFS/ME services provided no service for housebound patients. 55% (27/49) services did treat patients with severe CFS/ME and their interventions followed the NICE guidelines. The remaining services (12%, 6/49) offered occasional or minimal support where funding allowed. There was one NHS unit providing specialist inpatient CFS/ME provision in England.
Study findings highlight substantial variation in access to specialist care for patients with severe presentation of CFS/ME. Where treatment was provided, this appeared to comply with NICE recommendations for this patient group.
Neurology; Primary Care
In a recent individual patient data meta-analysis, acupuncture was found to be superior to both sham and non-sham controls in patients with chronic pain. In this paper we identify variations in types of sham and non-sham controls used and analyze their impact on the effect size of acupuncture.
Based on literature searches of acupuncture trials involving patients with headache and migraine, osteoarthritis, and back, neck and shoulder pain, 29 trials met inclusion criteria, 20 involving sham controls (n = 5,230) and 18 non-sham controls (n = 14,597). For sham controls, we analysed non-needle sham, penetrating sham needles and non-penetrating sham needles. For non-sham controls, we analysed non-specified routine care and protocol-guided care. Using meta-regression we explored impact of choice of control on effect of acupuncture.
Acupuncture was significantly superior to all categories of control group. For trials that used penetrating needles for sham control, acupuncture had smaller effect sizes than for trials with non-penetrating sham or sham control without needles. The difference in effect size was −0.45 (95% C.I. −0.78, −0.12; p = 0.007), or −0.19 (95% C.I. −0.39, 0.01; p = 0.058) after exclusion of outlying studies showing very large effects of acupuncture. In trials with non-sham controls, larger effect sizes associated with acupuncture vs. non-specified routine care than vs. protocol-guided care. Although the difference in effect size was large (0.26), it was not significant with a wide confidence interval (95% C.I. −0.05, 0.57, p = 0.1).
Acupuncture is significantly superior to control irrespective of the subtype of control. While the choice of control should be driven by the study question, our findings can help inform study design in acupuncture, particularly with respect to sample size. Penetrating needles appear to have important physiologic activity. We recommend that this type of sham be avoided.
To systematically review the literature pertaining to the prevalence of depression and anxiety in patients with prostate cancer as a function of treatment stage.
Systematic review and meta-analysis.
4494 patients with prostate cancer from primary research investigations.
Primary outcome measure
The prevalence of clinical depression and anxiety in patients with prostate cancer as a function of treatment stage.
We identified 27 full journal articles that met the inclusion criteria for entry into the meta-analysis resulting in a pooled sample size of 4494 patients. The meta-analysis of prevalence rates identified pretreatment, on-treatment and post-treatment depression prevalences of 17.27% (95% CI 15.06% to 19.72%), 14.70% (95% CI 11.92% to 17.99%) and 18.44% (95% CI 15.18% to 22.22%), respectively. Pretreatment, on-treatment and post-treatment anxiety prevalences were 27.04% (95% CI 24.26% to 30.01%), 15.09% (95% CI 12.15% to 18.60%) and 18.49% (95% CI 13.81% to 24.31%), respectively.
Our findings suggest that the prevalence of depression and anxiety in men with prostate cancer, across the treatment spectrum, is relatively high. In light of the growing emphasis placed on cancer survivorship, we consider that further research within this area is warranted to ensure that psychological distress in patients with prostate cancer is not underdiagnosed and undertreated.
MENTAL HEALTH; STATISTICS & RESEARCH METHODS
In September 2012, the Acupuncture Trialists' Collaboration published the results of an individual patient data meta-analysis of close to 18,000 patients in high quality-randomized trials. The results favored acupuncture. Although there was little argument about the findings in the scientific press, a controversy played out in blog posts and the lay press. This controversy was characterized by ad hominem remarks, anonymous criticism, phony expertise, and the use of opinion to contradict data, predominately by self-proclaimed skeptics. There was a near complete absence of substantive scientific critque. The lack of any reasoned debate about the main findings of the Acupuncture Trialists' Collaboration paper underlines that mainstream science has moved on from the intellectual sterility and ad hominem attacks that characterize the skeptics’ movement.
Pain; Skepticism; Headache; Acupuncture; Statistics and Research Design
The use of complementary and alternative Medicine (CAM) has increased over the past two decades in Europe. Nonetheless, research investigating the evidence to support its use remains limited. The CAMbrella project funded by the European Commission aimed to develop a strategic research agenda starting by systematically evaluating the state of CAM in the EU. CAMbrella involved 9 work packages covering issues such as the definition of CAM; its legal status, provision and use in the EU; and a synthesis of international research perspectives. Based on the work package reports, we developed a strategic and methodologically robust research roadmap based on expert workshops, a systematic Delphi-based process and a final consensus conference. The CAMbrella project suggests six core areas for research to examine the potential contribution of CAM to the health care challenges faced by the EU. These areas include evaluating the prevalence of CAM use in Europe; the EU cititzens’ needs and attitudes regarding CAM; the safety of CAM; the comparative effectiveness of CAM; the effects of meaning and context on CAM outcomes; and different models for integrating CAM into existing health care systems. CAM research should use methods generally accepted in the evaluation of health services, including comparative effectiveness studies and mixed-methods designs. A research strategy is urgently needed, ideally led by a European CAM coordinating research office dedicated to fostering systematic communication between EU governments, the public, charitable and industry funders, researchers and other stakeholders. A European Centre for CAM should also be established to monitor and further a coordinated research strategy with sufficient funds to commission and promote high quality, independent research focusing on the public’s health needs and pan-European collaboration. There is a disparity between highly prevalent use of CAM in Europe and solid knowledge about it. A strategic approach on CAM research should be established to investigate the identified gaps of knowledge and to address upcoming health care challenges.
Complementary and alternative medicine; Research strategy; Randomized clinical trials; Safety; Qualitative studies; Comparative effectiveness research
Digital interventions are becoming an increasingly popular method of delivering healthcare as they enable and promote patient self-management. This paper provides a methodological guide to the processes involved in developing effective digital interventions, detailing how to plan and develop such interventions to avoid common pitfalls. It demonstrates the need for mixed qualitative and quantitative methods in order to develop digital interventions which are effective, feasible, and acceptable to users and stakeholders.
A large number of infertile couples are choosing Chinese herbal medicine (CHM) as an adjuvant therapy to improve their success when undergoing in vitro fertilization (IVF). There is no systematic review to evaluate the impact of CHM on the IVF outcomes.
To evaluate the effectiveness of CHM with concurrent IVF versus IVF alone on the outcomes of IVF and its safety.
The protocol of this study is registered at PROSPERO. Eligible RCTs searched from 8 databases which compared a combination of CHM and IVF with IVF alone were included. Two authors independently selected studies, extracted data and assessed methodological quality. Meta-analysis of RCTs was conducted if there was non-significant heterogeneity (evaluated by I2 test) among trials. All statistical analysis was performed using RevMan 5.1 software.
Twenty trials involving 1721 women were included in the meta-analysis. Three trials were evaluated as having an unclear risk of bias. The remaining trials were evaluated as having a high risk of bias. Combination of CHM and IVF significantly increases clinical pregnancy rates (OR 2.04, 95%CI 1.67 to 2.49, p<0.00001) and ongoing pregnancy rates (OR 1.91, 95%CI 1.17 to 3.10, p = 0.009). Use of CHM after embryo transfer had no better outcome in reducing the rate of ovarian hyper stimulation syndrome (OR 0.39, 95%CI 0.14 to 1.11, p = 0.08).
This meta-analysis showed that combination of IVF and CHM used in the included trials improve IVF success, however due to the high risk of bias observed with the trials, the significant differences found with the meta-analysis are unlikely to be accurate. No conclusion could be drawn with respect to the reproductive toxicity of CHM. Further large randomized placebo controlled trials are warranted to confirm these findings before recommending women to take CHM to improve their IVF success.
Although acupuncture is widely used for chronic pain, there remains considerable controversy as to its value. We aimed to determine the effect size of acupuncture for four chronic pain conditions: back and neck pain, osteoarthritis, chronic headache, and shoulder pain.
We conducted a systematic review to identify randomized trials of acupuncture for chronic pain where allocation concealment was determined unambiguously to be adequate. Individual patient data meta-analyses were conducted using data from 29 of 31 eligible trials, with a total of 17,922 patients analyzed.
In the primary analysis including all eligible trials, acupuncture was superior to both sham and no acupuncture control for each pain condition (all p<0.001). After exclusion of an outlying set of trials that strongly favored acupuncture, the effect sizes were similar across pain conditions. Patients receiving acupuncture had less pain, with scores 0.23 (95% C.I. 0.13, 0.33), 0.16 (95% C.I. 0.07, 0.25) and 0.15 (95% C.I. 0.07, 0.24) standard deviations lower than sham controls for back and neck pain, osteoarthritis, and chronic headache respectively; the effect sizes in comparison to no acupuncture controls were 0.55 (95% C.I. 0.51, 0.58), 0.57 (95% C.I. 0.50, 0.64) and 0.42 (95% C.I. 0.37, 0.46). These results were robust to a variety of sensitivity analyses, including those related to publication bias.
Acupuncture is effective for the treatment of chronic pain and is therefore a reasonable referral option. Significant differences between true and sham acupuncture indicate that acupuncture is more than a placebo. However, these differences are relatively modest, suggesting that factors in addition to the specific effects of needling are important contributors to the therapeutic effects of acupuncture.
Recent evidence shows that acupuncture is effective for chronic pain. However we do not know whether there are characteristics of acupuncture or acupuncturists that are associated with better or worse outcomes.
An existing dataset, developed by the Acupuncture Trialists’ Collaboration, included 29 trials of acupuncture for chronic pain with individual data involving 17,922 patients. The available data on characteristics of acupuncture included style of acupuncture, point prescription, location of needles, use of electrical stimulation and moxibustion, number, frequency and duration of sessions, number of needles used and acupuncturist experience. We used random-effects meta-regression to test the effect of each characteristic on the main effect estimate of pain. Where sufficient patient-level data were available, we conducted patient-level analyses.
When comparing acupuncture to sham controls, there was little evidence that the effects of acupuncture on pain were modified by any of the acupuncture characteristics evaluated, including style of acupuncture, the number or placement of needles, the number, frequency or duration of sessions, patient-practitioner interactions and the experience of the acupuncturist. When comparing acupuncture to non-acupuncture controls, there was little evidence that these characteristics modified the effect of acupuncture, except better pain outcomes were observed when more needles were used (p=0.010) and, from patient level analysis involving a sub-set of five trials, when a higher number of acupuncture treatment sessions were provided (p<0.001).
There was little evidence that different characteristics of acupuncture or acupuncturists modified the effect of treatment on pain outcomes. Increased number of needles and more sessions appear to be associated with better outcomes when comparing acupuncture to non-acupuncture controls, suggesting that dose is important. Potential confounders include differences in control group and sample size between trials. Trials to evaluate potentially small differences in outcome associated with different acupuncture characteristics are likely to require large sample sizes.
Clinical trials on Traditional Chinese Medicine (TCM) should be registered in a publicly accessible international trial register and report on all outcomes. We systematically assessed and evaluated TCM trials in registries with their subsequent publications.
To describe the characteristics of TCM trials, estimate bias risk and outcome-reporting bias in clinical trials.
Data sources and study selection
Fifteen trial registries were searched from their inception to July 2012 to identify randomised trials on TCM including Chinese herbs, acupuncture and/or moxibustion, cupping, tuina, qigong, etc.
We extracted data including TCM specialty and treated disease/conditions from the registries and searched for subsequent publications in PubMed and Chinese databases. We compared information in the registries of completed trials with any publications focusing on study design, sample size, randomisation, bias risk including reporting bias from the register protocol.
1096 registered randomised trials were identified evaluating TCM, of which 505 were completed studies (46.1%). The most frequent conditions were pain (13.3%), musculoskeletal (11.7%), nervous (8.7%), digestive (7.1%), circulatory (6.5%), respiratory (6.3%), mental and behavioural disorders (6.2%) and cancer (6.0%). The trial register data identified parallel, phase II/III randomised trials with sample size estimations and blinding, but limited information about randomisation (sequence generation and allocation concealment). Comparing trial registration data of 115 completed trials (22.8%) with their subsequent 136 publications, inconsistencies were identified in one or more of the following: sample size (11%), outcome assessor blinding (37.5%), primary outcomes (29%) and safety (28%) reporting.
Increasing numbers of clinical trials investigating a variety of TCM interventions have been registered in international trial registries. The study design of registered TCM trials has improved in estimating sample size, use of blinding and placebos. However, selective outcome reporting is widespread and similar to conventional medicine and therefore study conclusions should be interpreted with caution.
Current evidence-based guidelines for low back pain (LBP) recommend multiple diverse approaches to treatment and suggest considering patient preferences when formulating a treatment plan.
To explore patient preferences and to identify patients’ beliefs about LBP treatments.
Design and setting
Qualitative study using focus groups in primary care in South-West England.
Thirteen focus groups were organised with a purposive sample of 75 adults with LBP. Group discussions of LBP treatments were facilitated, audiorecorded, and the verbatim transcripts thematically analysed.
Eight themes were identified, four related to treatment beliefs and four to seeking treatment. Treatment beliefs comprised participants’ expectations and appraisals of specific treatments, which were underpinned by four distinct dimensions: credibility, effectiveness, concerns and individual fit. Treatment beliefs were expressed in the broader context of treatment seeking: participants’ primary concern was to obtain a clear explanation of their LBP which went beyond a diagnostic label and provided an understanding of the cause(s) of their LBP. They described engaging in self-management activities and claimed they were willing to try anything if it might help them. Participants wanted an empathic and expert practitioner who could deliver a suitable treatment (or refer them on to someone else) and help them to negotiate the challenges of the healthcare system.
These findings highlight the importance of helping patients develop coherent illness representations about their LBP before trying to engage them in treatment-decisions, uptake, or adherence. Addressing patients’ illness and treatment perceptions in clinical practice could improve shared decision making and patient outcomes.
back pain; health knowledge, attitudes, practice; illness behaviour; patient preference; primary health care; qualitative research
Like any other form of healthcare, acupuncture takes place in a particular context which can enhance or diminish treatment outcomes (i.e. can produce contextual effects). Patients’ expectations of acupuncture might be an important component of contextual effects, but we know relatively little about the origins and nature of patients’ expectations or wider preconceptions about acupuncture. Our aim was to identify the processes the underpin patients’ decisions to try acupuncture and thus begin to tease out the origins and nature of patients’ preconceptions.
One-off semi-structured interviews were conducted with a purposive, varied sample of 35 adults who had tried acupuncture for various conditions. Interviews explored people’s experiences of acupuncture treatment and techniques from framework and inductive thematic analysis were used to relate the data to the research question.
We identified four distinct processes within participants’ accounts of deciding to try acupuncture: establishing a need for treatment, establishing a need for a new treatment, deciding to try acupuncture, and finding an acupuncturist. Family, friends and health care professionals played a role in these processes, providing support, advice, and increasing people’s general familiarity with acupuncture. When they came to their first acupuncture appointment, participants had hopes, concerns, and occasionally concrete expectations as to the nature of acupuncture treatment and its likely effects.
Existing theories of how context influences health outcomes could be expanded to better reflect the psychological components identified here, such as hope, desire, optimism and open-mindedness. Future research on the context of acupuncture should consider these elements of the pre-treatment context in addition to more established components such as expectations. There appears to be a need for accessible (i.e. well-disseminated), credible, and individualised, patient-centred materials that can allay people’s concerns about the nature of acupuncture treatment and shape realistic hopes and expectations.
Placebo; Context; Acupuncture; Health care utilisation; Complementary medicine; Expectations; Health knowledge attitudes practice; Illness behaviour; Qualitative research; Patient preference; Treatment seeking
Surveys in various countries suggest 17% to 80% of doctors prescribe ‘placebos’ in routine practice, but prevalence of placebo use in UK primary care is unknown.
We administered a web-based questionnaire to a representative sample of UK general practitioners. Following surveys conducted in other countries we divided placebos into ‘pure’ and ‘impure’. ‘Impure’ placebos are interventions with clear efficacy for certain conditions but are prescribed for ailments where their efficacy is unknown, such as antibiotics for suspected viral infections. ‘Pure’ placebos are interventions such as sugar pills or saline injections without direct pharmacologically active ingredients for the condition being treated. We initiated the survey in April 2012. Two reminders were sent and electronic data collection closed after 4 weeks.
We surveyed 1715 general practitioners and 783 (46%) completed our questionnaire. Our respondents were similar to those of all registered UK doctors suggesting our results are generalizable. 12% (95% CI 10 to 15) of respondents used pure placebos while 97% (95% CI 96 to 98) used impure placebos at least once in their career. 1% of respondents used pure placebos, and 77% (95% CI 74 to 79) used impure placebos at least once per week. Most (66% for pure, 84% for impure) respondents stated placebos were ethical in some circumstances.
Conclusion and implications
Placebo use is common in primary care but questions remain about their benefits, harms, costs, and whether they can be delivered ethically. Further research is required to investigate ethically acceptable and cost-effective placebo interventions.
The increasing burden of chronic diseases presents not only challenges to the knowledge and expertise of the professional medical community, but also highlights the need to improve the quality and relevance of clinical research in this domain. Many patients now turn to complementary and integrative medicine (CIM) to treat their chronic illnesses; however, there is very little evidence to guide their decision-making in usual care. The following research recommendations were derived from a CIM Stakeholder Symposium on Comparative Effectiveness Research (CER): (1) CER studies should be made a priority in this field; (2) stakeholders should be engaged at every stage of the research; (3) CER study designs should highlight effectiveness over efficacy; (4) research questions should be well defined to enable the selection of an appropriate CER study design; (5) the CIM community should cultivate widely shared understandings, discourse, tools, and technologies to support the use and validity of CER methods; (6) Effectiveness Guidance Documents on methodological standards should be developed to shape future CER studies. CER is an emerging field and its development and impact must be reflected in future research strategies within CIM. This stakeholder symposium was a first step in providing systematic guidance for future CER in this field.
Hypercholesterolemia is an important key contributory factor for ischemic heart disease and is associated with age, high blood pressure, a family history of hypercholesterolemia, and diabetes. Chinese herbal medicines have been used for a long time as lipid-lowering agents.
To assess the effects of Chinese herbal medicines on hypercholesterolemia.
We searched the following databases: The Cochrane Library (issue 8, 2010), MEDLINE (until July 2010), EMBASE (until July 2010), Chinese BioMedical Database (until July 2010), Traditional Chinese Medical Literature Analysis and Retrieval System (until July 2010), China National Knowledge Infrastructure (until July 2010), Chinese VIP Information (until July 2010), Chinese Academic Conference Papers Database and Chinese Dissertation Database (until July 2010), and Allied and Complementary Medicine Database (until July 2010).
We considered randomized controlled clinical trials in hypercholesterolemic participants comparing Chinese herbal medicines with placebo, no treatment, and pharmacological or non-pharmacological interventions.
Data collection and analysis
Two review authors independently extracted data and assessed the risk of bias. We resolved any disagreements with this assessment through discussion and a decision was achieved based by consensus. We assessed trials for the risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, incomplete outcome data, selective outcome reporting and other sources of bias.
We included 22 randomized trials (2130 participants). The mean treatment duration was 2.3 ± 1.3 months (ranging from one to six months). Twenty trials were conducted in China and 18 trials were published in Chinese. Overall, the risk of bias of included trials was high or unclear. Five different herbal medicines were evaluated in the included trials, which compared herbs with conventional medicine in six comparisons (20 trials), or placebo (two trials). There were no outcome data in any of the trials on cardiovascular events and death from any cause. One trial each reported well-being (no significant differences) and economic costs. No serious adverse events were observed. Xuezhikang was the most commonly used herbal formula investigated. A significant effect on total cholesterol (two trial, 254 participants) was shown in favor of Xuezhikang when compared with inositol nicotinate (mean difference (MD) −0.90 mmol/L, 95% confidence interval (CI) −1.13 to −0.68) .
Some herbal medicines may have cholesterol-lowering effects. Our findings have to be interpreted with caution due to high or unclear risk of bias of the included trials.
Placebo groups are used in randomised clinical trials (RCTs) to control for placebo effects, which can be large. Participants in trials can misunderstand written information particularly regarding technical aspects of trial design such as randomisation; the adequacy of written information about placebos has not been explored. We aimed to identify what participants in major RCTs in the UK are told about placebos and their effects.
Methods and Findings
We conducted a content analysis of 45 Participant Information Leaflets (PILs) using quantitative and qualitative methodologies. PILs were obtained from trials on a major registry of current UK clinical trials (the UKCRN database). Eligible leaflets were received from 44 non-commercial trials but only 1 commercial trial. The main limitation is the low response rate (13.5%), but characteristics of included trials were broadly representative of all non-commercial trials on the database. 84% of PILs were for trials with 50∶50 randomisation ratios yet in almost every comparison the target treatments were prioritized over the placebos. Placebos were referred to significantly less frequently than target treatments (7 vs. 27 mentions, p<001) and were significantly less likely than target treatments to be described as triggering either beneficial effects (1 vs. 45, p<001) or adverse effects (4 vs. 39, p<001). 8 PILs (18%) explicitly stated that the placebo treatment was either undesirable or ineffective.
PILs from recent high quality clinical trials emphasise the benefits and adverse effects of the target treatment, while largely ignoring the possible effects of the placebo. Thus they provide incomplete and at times inaccurate information about placebos. Trial participants should be more fully informed about the health changes that they might experience from a placebo. To do otherwise jeopardises informed consent and is inconsistent with not only the science of placebos but also the fundamental rationale underpinning placebo controlled trials.