Trials - Latest Articles

Obstacles to researching the researchers: A case study of the ethical challenges of undertaking methodological research investigating the reporting of randomised controlled trials

Joanne McKenzie — 2010-03-21T00:00:00Z

Background: Recent cohort studies of randomised controlled trials have provided evidence of within-study selective reporting bias; where statistically significant outcomes are more likely to be more completely reported compared to non-significant outcomes. Bias resulting from selective reporting can impact on meta-analyses, influencing the conclusions of systematic reviews, and in turn, evidence based clinical practice guidelines.In 2006 we received funding to investigate if there was evidence of within-study selective reporting in a cohort of RCTs submitted to New Zealand Regional Ethics Committees in 1998/99. This research involved accessing ethics applications, their amendments and annual reports, and comparing these with corresponding publications. We did not plan to obtain informed consent from trialists to view their ethics applications for practical and scientific reasons.In November 2006 we sought ethical approval to undertake the research from our institutional ethics committee. The Committee declined our application on the grounds that we were not obtaining informed consent from the trialists to view their ethics application. This initiated a seventeen month process to obtain ethical approval. This publication outlines what we planned to do, the issues we encountered, discusses the legal and ethical issues, and presents some potential solutions.Discussion and conclusionMethodological research such as this has the potential for public benefit and there is little or no harm for the participants (trialists) in undertaking it. Further, in New Zealand, there is freedom of information legislation, which in this circumstance, unambiguously provided rights of access and use of the information in the ethics applications. The decision of our institutional ethics committee defeated this right and did not recognise the nature of this observational research.Methodological research, such as this, can be used to develop processes to improve quality in research reporting. Recognition of the potential benefit of this research in the broader research community, and those who sit on ethics committees, is perhaps needed. In addition, changes to the ethical review process which involve separation between those who review proposals to undertake methodological research using ethics applications, and those with responsibility for reviewing ethics applications for trials, should be considered. Finally, we contend that the research community could benefit from quality improvement approaches used in allied sectors.

JinQi-Jiangtang tablet, a Chinese patent medicine, for pre-diabetes: a randomized controlled trial

Hongbo Cao — 2010-03-10T00:00:00Z

Background: Pre-diabetes is a growing health concern where a large percentage of these patients develop full type 2 diabetes. Effective interventions on pre-diabetes can prevent or delay the occurrence or development of diabetes. Pharmaco-dynamics and pre-clinical of JinQi-Jiangtang tablets (JQJT) suggest that it could be benefit for pre-diabetes.Methods/DesignRandomized controlled trial (RCT) is implemented in this study. The study term is 24 months (12 months for intervention and 12 months for follow up). Participants are recruited from four cities of China: Beijing, Tianjin, Xi'an and Nanning. Four hundred participants are randomized to treatment group (JQJT tablets) and control group (Placebo); two hundred participants each. People being included in this study must have been diagnosed as pre-diabetes via western medicine criteria and traditional Chinese medicine (TCM) criteria. The end-point indexes include: incidence of diabetes mellitus and reversion rate. Primary outcome indexes include: oral glucose tolerance test; insulin releasing test; glycosylated hemoglobin (HA1c). Secondary outcome indexes include: score of the Short Form 36 Health Survey Questionnaire (SF-36); score of TCM symptoms; blood lipid test. Indexes of safety include: general medical examination; blood and urine regular test; electrocardiogram (ECG), liver function (ALT) and renal function (BUN, Creatinine) test; record of adverse event, such as headache, faint, etc. Qualitative control will be implemented and a number of standard operating processes (SOPs) will be formed throughout the study: laboratory quality control measures; compliance control for researchers and participants; researcher training before study; supervision; investigational drug management and others.DiscussionThe aim of this study is to evaluate the effectiveness and safety of JinQi JiangTang (JQJT) tablets for the treatment of patients with pre-diabetes.Trial registrationChinese clinical trials register ChiCTR-TRC-00000401

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

Carolina Weller — 2010-03-09T00:00:00Z

Background: The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression. Methods: The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size [less than or equal to]10cm2 or >10cm2.. Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process.DiscussionThe aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes.Trial Registration: ACTRN12608000599370

The effectiveness of a web-based self-help intervention to reduce suicidal thoughts: A randomized controlled trial

Bregje van Spijker — 2010-03-09T00:00:00Z

Background: Suicide, attempted suicide and suicidal thoughts are major public health problems worldwide. Effective face-to-face treatments are Cognitive Behavioural Therapy (CBT), Dialectical Behavioural Therapy (DBT) and Problem Solving Treatment (PST). However, about two-thirds of persons who die by suicide have not been in contact with mental health care services in the preceding year, and many have never been treated. Furthermore, many patients do not disclose their suicidal thoughts to their care provider. This may be out of shame, due to fear of stigma or due to lack of trust in (mental) health care. Since many suicidal individuals seek information online, the internet provides an opportunity to reach suicidal individuals who would not be contacted otherwise. By providing a self-help intervention online, persons can anonymously learn to gain control over their suicidal thoughts. There is convincing evidence that self-help is effective for a number of mental disorders. In this study the effectiveness for suicidal thoughts is examined.Methods/DesignIn this study, a recently developed self-help intervention will be evaluated in a Randomized Controlled Trial. The intervention is based on Cognitive Behavioural Therapy and is aimed at subjects who experience mild to moderate suicidal thoughts. This is defined as a score between 1 and 26 on the Beck Scale for Suicidal Ideation (BSS). Higher and lower scores are excluded. In addition, severely depressed subjects are excluded. In total, 260 subjects will be randomly allocated to the intervention-condition (N = 130) or to the information-control condition (N = 130). Self-report questionnaires will be filled out at baseline, 6 weeks after baseline and 18 weeks after baseline. Primary outcome measure is the reduction in frequency and intensity of suicidal thoughts. Secondary outcome measures are the reduction of hopelessness, anxiety and depression, sleeplessness, worry and quality of life measures.DiscussionThis study is the first to evaluate the effectiveness of a web-based self-help intervention for suicidal thoughts. Several limitations and strengths of the design are discussed.Trial RegistrationNetherlands Trial Register, NTR1689

Individualized chiropractic and integrative care for low back pain: the design of a randomized clinical trial using a mixed-methods approach

Kristine Westrom — 2010-03-08T00:00:00Z

Background: Low back pain (LBP) is a prevalent and costly condition in the United States. Evidence suggests there is no one treatment which is best for all patients, but instead several viable treatment options. Additionally, multidisciplinary management of LBP may be more effective than monodisciplinary care. An integrative model that includes both complementary and alternative medicine (CAM) and conventional therapies, while also incorporating patient choice, has yet to be tested for chronic LBP.The primary aim of this study is to determine the relative clinical effectiveness of 1) monodisciplinary chiropractic care and 2) multidisciplinary integrative care in 200 adults with non-acute LBP, in both the short-term (after 12 weeks) and long-term (after 52 weeks). The primary outcome measure is patient-rated back pain. Secondary aims compare the treatment approaches in terms of frequency of symptoms, low back disability, fear avoidance, self-efficacy, general health status, improvement, satisfaction, work loss, medication use, lumbar dynamic motion, and torso muscle endurance. Patients' and providers' perceptions of treatment will be described using qualitative methods, and cost-effectiveness and cost utility will be assessed.Methods and DesignThis paper describes the design of a randomized clinical trial (RCT), with cost-effectiveness and qualitative studies conducted alongside the RCT. Two hundred participants ages 18 and older are being recruited and randomized to one of two 12-week treatment interventions. Patient-rated outcome measures are collected via self-report questionnaires at baseline, and at 4, 12, 26, and 52 weeks post-randomization. Objective outcome measures are assessed at baseline and 12 weeks by examiners blinded to treatment assignment. Health care cost data is collected by self-report questionnaires and treatment records during the intervention phase and by monthly phone interviews thereafter. Qualitative interviews, using a semi-structured format, are conducted with patients at the end of the 12-week treatment period and also with providers at the end of the trial.DiscussionThis mixed-methods randomized clinical trial assesses clinical effectiveness, cost-effectiveness, and patients' and providers' perceptions of care, in treating non-acute LBP through evidence-based individualized care delivered by monodisciplinary or multidisciplinary care teams.Trial registrationClinicalTrials.gov NCT00567333

Correction: Protocol for the PINCER trial: a cluster randomised trial comparing the effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Anthony Avery — 2010-03-02T00:00:00Z

No description available

Studying a disease with no home - lessons in trial recruitment from the PATCH II study

Kim Thomas — 2010-03-02T00:00:00Z

Background: Cellulitis is a very common condition that often recurs. The PATCH II study was designed to explore the possibility of preventing future episodes of cellulitis, with resultant cost savings for the NHS. This was the first trial to be undertaken by the UK Dermatology Clinical Trials Network. As such, it was the first to test a recruitment model that involved many busy clinicians each contributing just a few patients. Methods: A double-blind randomised controlled trial comparing prophylactic antibiotics (penicillin V) with placebo tablets, for the prevention of repeat episodes of cellulitis of the leg. Primary outcome was time to subsequent recurrence of cellulitis. Results: The PATCH II study was closed to recruitment having enrolled 123 participants from a target of 400. Whilst the recruitment period was extended by 12 months, it was not possible to continue beyond this point without additional funds. Many factors contributed to poor recruitment: (i) changes in hospital policy and the introduction of community-based intravenous teams resulted in fewer cellulitis patients being admitted to hospital; ii) those who were admitted were seen by many different specialties, making it difficult for a network of dermatology clinicians to identify suitable participants; and iii) funding for research staff was limited to a trial manager and a trial administrator at the co-ordinating centre. With no dedicated research nurses at the recruiting centres, it was extremely difficult to maintain momentum and interest in the study. Attempts to boost recruitment by providing some financial support for principal investigators to employ local research staff was of limited success.DiscussionThe model of a network of busy NHS clinicians all recruiting a few patients into large clinical studies requires further testing. It did not work very well for PATCH II, but this was probably because patients were not routinely seen by dermatologists, and recruitment took place prior to research support being available through the Comprehensive Clinical Research Network (CCRN). There is a balance to be struck between asking a lot of centres to recruit just a few patients, and asking a few centres to recruit a lot of patients. Giving modest funds to principal investigators to buy local research nurse time did not work well, probably because too little research time was bought, and it was difficult to separate research tasks from the nurses existing clinical duties. National research infrastructure networks such as the Comprehensive Clinical Research Network will overcome many of the problems encountered in the PATCH II trial.Trial RegistrationThe trial registration number is ISRCTN03813200.

Rationale and design of the randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with Major Depressive Disorder - the EMC trial

Andre Tadic — 2010-02-26T00:00:00Z

Background: In Major Depressive Disorder (MDD), the traditional belief of a delayed onset of antidepressants' effects has lead to the concept of current guidelines that treatment durations should be between 3-8 weeks before medication change in case of insufficient outcome. Post hoc analyses of clinical trials, however, have shown that improvement usually occurs within the first 10-14 days of treatment and that such early improvement (Hamilton Depression Rating Scale [HAMD] decrease ≥20%) has a substantial predictive value for final treatment outcome. Even more important, non-improvement (HAMD decrease <20%) after 14 days of treatment was found to be highly predictive for a poor final treatment outcome.Methods/DesignThe EMC trial is a phase IV, multi-centre, multi-step, randomized, observer-blinded, actively controlled parallel-group clinical trial to investigate for the first time prospectively, whether non-improvers after 14 days of antidepressant treatment with an early medication change (EMC) are more likely to attain remission (HAMD-17 ≤7) on treatment day 56 compared to patients treated according to current guideline recommendation (treatment as usual; TAU). In level 1 of the EMC trial, non-improvers after 14 days of antidepressant treatment will be randomised to an EMC strategy or TAU. The EMC strategy for this study schedules a first medication change on day 15; in case of non-improvement between days 15-28, a second medication change will be performed. TAU schedules the first medication change after 28 days in case of non-response (HAMD-17 decrease <50%). Both interventions will last 42 days. In levels 2 and 3, EMC strategies will be compared with TAU strategies in improvers on day 14, who experience a stagnation of improvement during the course of treatment. The trial is supported by the German Federal Ministry of Education and Research (BMBF) and will be conducted in cooperation with the BMBF funded Interdisciplinary Centre Clinical Trials (IZKS) at the University Medical Centre Mainz and at six clinical trial sites in Germany.DiscussionIf the EMC strategies lead to significantly more remitters, changes of clinical practice, guidelines for the treatment of MDD as well as research settings can be expected.Trial RegistrationClincaltrials.gov Identifier: NCT00974155; EudraCT: 2008-008280-96.

Applicability and generalisability of the results of systematic reviews to public health practice and policy: a systematic review

Nizar Ahmad — 2010-02-26T00:00:00Z

Background: The purpose of the study was to evaluate systematic reviews of research into two public health priorities, tobacco consumption and HIV infection, in terms of the reporting of data related to the applicability of trial results (i.e., whether the results of a trial can be reasonably applied or generalized to a definable group of patients in a particular setting in routine practice, also called external validity or generalisability). Methods: All systematic reviews of interventions aimed at reducing or stopping tobacco use and treating or preventing HIV infection published in the Cochrane database of systematic reviews and in journals indexed in MEDLINE between January 1997 and December 2007 were selected. We used a standardized data abstraction form to extract data related to applicability in terms of the context of the trial, (country, centres, settings), participants (recruitment, inclusion and exclusion criteria, baseline characteristics of participants such as age, sex, ethnicity, coexisting diseases or co-morbidities, and socioeconomic status), treatment (duration, intensity/dose of treatment, timing and delivery format), and the outcomes assessment from selected reviews. Results: A total of 98 systematic reviews were selected (57 Cochrane reviews and 41 non-Cochrane reviews); 49 evaluated interventions aimed at reducing or stopping tobacco use and 49 treating or preventing HIV infection. The setting of the individual studies was reported in 45 (46%) of the systematic reviews, the number of centres in 21 (21%), and the country where the trial took place in 62 (63%). Inclusion and exclusion criteria of the included studies were reported in 16 (16%) and 13 (13%) of the reviews, respectively. Baseline characteristics of participants in the included studies were described in 59 (60%) of the reviews. These characteristics concerned age in about half of the reviews, sex in 46 (47%), and ethnicity in 9 (9%).Applicability of results was discussed in 13 (13%) of the systematic reviews. The reporting was better in systematic reviews by the Cochrane Collaboration than by non-Cochrane groups. Conclusions: Our study highlighted the lack of consideration of applicability of results in systematic reviews of research into 2 public health priorities: tobacco consumption and HIV infection.

Prevention of depression and sleep disturbances in elderly with memory-problems by activation of the biological clock with light - a randomized clinical trial

Els Most — 2010-02-23T00:00:00Z

Background: Depression frequently occurs in the elderly and in patients suffering from dementia. Its cause is largely unknown, but several studies point to a possible contribution of circadian rhythm disturbances. Post-mortem studies on aging, dementia and depression show impaired functioning of the suprachiasmatic nucleus (SCN) which is thought to be involved in the increased prevalence of day-night rhythm perturbations in these conditions. Bright light enhances neuronal activity in the SCN. Bright light therapy has beneficial effects on rhythms and mood in institutionalized moderate to advanced demented elderly. In spite of the fact that this is a potentially safe and inexpensive treatment option, no previous clinical trial evaluated the use of long-term daily light therapy to prevent worsening of sleep-wake rhythms and depressive symptoms in early to moderately demented home-dwelling elderly.Methods/DesignThis study investigates whether long-term daily bright light prevents worsening of sleep-wake rhythms and depressive symptoms in elderly people with memory complaints. Patients with early Alzheimer's Disease (AD), Mild Cognitive Impairment (MCI) and Subjective Memory Complaints (SMC), between the ages of 50 and 75, are included in a randomized double-blind placebo-controlled trial. For the duration of two years, patients are exposed to ~10,000 lux in the active condition or ~300 lux in the placebo condition, daily, for two half-hour sessions at fixed times in the morning and evening. Neuropsychological, behavioral, physiological and endocrine measures are assessed at baseline and follow-up every five to six months.DiscussionIf bright light therapy attenuates the worsening of sleep-wake rhythms and depressive symptoms, it will provide a measure that is easy to implement in the homes of elderly people with memory complaints, to complement treatments with cholinesterase inhibitors, sleep medication or anti-depressants or as a stand-alone treatment.Trial registrationISRCTN29863753