Search

Abstract Background Homeopathy is often sought by patients with depression. In classical homeopathy, the treatment consists of two main elements: the case history and the prescription of an individually selected homeopathic remedy. Previous data suggest that individualized homeopathic Q-potencies were not inferior to the antidepressant fluoxetine in a sample of patients with moderate to severe depression. However, the question remains whether individualized homeopathic Q-potencies and/or the type of the homeopathic case history have a specific therapeutical effect in acute depression as this has not yet been investigated. The study aims to assess the two components of individualized homeopathic treatment for acute depression, i.e., to investigate the specific effect of individualized Q-potencies versus placebo and to investigate the effect of different approaches to the homeopathic case history. Methods/Design A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2 × 2 factorial design with a six-week study duration per patient will be performed. 228 patients diagnosed with major depression (moderate episode) by a psychiatrist will be included. The primary endpoint is the total score on the 17-item Hamilton Depression Rating Scale after six weeks. Secondary end points are: Hamilton Depression Rating Scale total score after two and four weeks; response and remission rates, Beck Depression inventory total score, quality of life and safety at two, four and six weeks. Statistical analyses will be by intention-to-treat. The main endpoint will be analysed by a two-factorial analysis of covariance. Within this model generalized estimation equations will be used to estimate differences between verum and placebo, and between both types of case history. Discussion For the first time this study evaluates both the specific effect of homeopathic medicines and of a homeopathic case taking in patients with depression. It is an attempt to deal with the challenges of homeopathic research and the results might be useful information in the current discussion about the evidence on homeopathy Trial registration ClinicalTrials.gov: NCT01178255

Abstract Background The purpose of clinical trials of acupuncture is to help clinicians and patients make decisions about treatment. Yet this is not straightforward: some trials report acupuncture to be superior to sham (placebo) acupuncture while others show evidence that acupuncture is superior to usual care but not sham, and still others conclude that acupuncture is no better than usual care. Meta-analyses of these trials tend to come to somewhat indeterminate conclusions. This appears to be because, until recently, acupuncture research was dominated by small trials of questionable quality. The Acupuncture Trialists' Collaboration, a group of trialists, statisticians and other researchers, was established to synthesize patient-level data from several recently published large, high-quality trials. Methods There are three distinct phases to the Acupuncture Trialists Collaboration: a systematic review to identify eligible studies; collation and harmonization of raw data; statistical analysis. To be eligible, trials must have unambiguous allocation concealment. Eligible pain conditions are osteoarthritis; chronic headache (tension or migraine headache); shoulder pain; and non-specific back or neck pain. Once received, patient-level data will undergo quality checks and the results of prior publications will be replicated. The primary analysis will be to determine the effect size of acupuncture. Each trial will be evaluated by analysis of covariance with the principal endpoint as the dependent variable and, as covariates, the baseline score for the principal endpoint and the variables used to stratify randomization. The effect size for acupuncture from each trial - that is, the coefficient and standard error from the analysis of covariance - will then be entered into a meta-analysis. We will compute effect sizes separately for comparisons of acupuncture with sham acupuncture, and acupuncture with no acupuncture control for each pain condition. Other analyses will investigate the impact of different sham techniques, styles of acupuncture or frequency and duration of treatment sessions. Discussion Individual patient data meta-analysis of high-quality trials will provide the most reliable basis for treatment decisions about acupuncture. Above all, however, we hope that our approach can serve as a model for future studies in acupuncture and other complementary therapies.

Background: Traumatic events like critical illness and intensive care are threats to life and bodily integrity and pose a risk factor for posttraumatic stress disorder (PTSD). PTSD affects the quality of life and morbidity and may increase health-care costs. Limited access to specialist care results in PTSD patients being treated in primary care settings. Narrative exposure therapy (NET) is based on the principles of cognitive behavioral therapy and has shown positive effects when delivered by health-care professionals other than psychologists. The primary aims of the PICTURE trial (from "PTSD after ICU survival") are to investigate the effectiveness and applicability of NET adapted for primary care with case management in adults diagnosed with PTSD after intensive care., Methods/design: This is an investigator-initiated, multi-center, primary care-based, randomized controlled two-arm parallel group, observer-blinded superiority trial conducted throughout Germany. In total, 340 adult patients with a total score of at least 20 points on the posttraumatic diagnostic scale (PDS-5) 3 months after receiving intensive care treatment will be equally randomized to two groups: NET combined with case management and improved treatment as usual (iTAU). All primary care physicians (PCPs) involved will be instructed in the diagnosis and treatment of PTSD according to current German guidelines. PCPs in the iTAU group will deliver usual care during three consultations. In the experimental group, PCPs will additionally be trained to deliver an adapted version of NET (three sessions) supported by phone-based case management by a medical assistant. At 6 and 12 months after randomization, structured blinded telephone interviews will assess patient-reported outcomes. The primary composite endpoint is the absolute change from baseline at month 6 in PTSD symptom severity measured by the PDS-5 total score, which also incorporates the death of any study patients. Secondary outcomes cover the domains depression, anxiety, disability, health-related quality-of-life, and cost-effectiveness. The principal analysis is by intention to treat., Discussion: If the superiority of the experimental intervention over usual care can be demonstrated, the combination of brief NET and case management could be a treatment option to relieve PTSD-related symptoms and to improve primary care after intensive care., Trial Registration: ClinicalTrials.gov, NCT03315390 . Registered on 10 October 2017. German Clinical Trials Register, DRKS00012589 . Registered on 17 October 2017.

Background: Selective reporting of outcomes in clinical trials is a serious problem. We aimed to investigate the influence of the peer review process within biomedical journals on reporting of primary outcome(s) and statistical analyses within reports of randomised trials., Methods: Each month, PubMed (May 2014 to April 2015) was searched to identify primary reports of randomised trials published in six high-impact general and 12 high-impact specialty journals. The corresponding author of each trial was invited to complete an online survey asking authors about changes made to their manuscript as part of the peer review process. Our main outcomes were to assess: (1) the nature and extent of changes as part of the peer review process, in relation to reporting of the primary outcome(s) and/or primary statistical analysis; (2) how often authors followed these requests; and (3) whether this was related to specific journal or trial characteristics., Results: Of 893 corresponding authors who were invited to take part in the online survey 258 (29%) responded. The majority of trials were multicentre (n = 191; 74%); median sample size 325 (IQR 138 to 1010). The primary outcome was clearly defined in 92% (n = 238), of which the direction of treatment effect was statistically significant in 49%. The majority responded (1-10 Likert scale) they were satisfied with the overall handling (mean 8.6, SD 1.5) and quality of peer review (mean 8.5, SD 1.5) of their manuscript. Only 3% (n = 8) said that the editor or peer reviewers had asked them to change or clarify the trial's primary outcome. However, 27% (n = 69) reported they were asked to change or clarify the statistical analysis of the primary outcome; most had fulfilled the request, the main motivation being to improve the statistical methods (n = 38; 55%) or avoid rejection (n = 30; 44%). Overall, there was little association between authors being asked to make this change and the type of journal, intervention, significance of the primary outcome, or funding source. Thirty-six percent (n = 94) of authors had been asked to include additional analyses that had not been included in the original manuscript; in 77% (n = 72) these were not pre-specified in the protocol. Twenty-three percent (n = 60) had been asked to modify their overall conclusion, usually (n = 53; 88%) to provide a more cautious conclusion., Conclusion: Overall, most changes, as a result of the peer review process, resulted in improvements to the published manuscript; there was little evidence of a negative impact in terms of post hoc changes of the primary outcome. However, some suggested changes might be considered inappropriate, such as unplanned additional analyses, and should be discouraged.

Background: Academic infrastructures and networks for clinical research in primary care receive little funding in Germany. We aimed to provide an overview of the quantity, topics, methods and findings of randomised controlled trials published by German university departments of general practice., Methods: We searched Scopus (last search done in April 2015), publication lists of institutes and references of included articles. We included randomised trials published between January 2000 and December 2014 with a first or last author affiliated with a German university department of general practice or family medicine. Risk of bias was assessed with the Cochrane tool, and study findings were quantified using standardised mean differences (SMDs)., Results: Thirty-three trials met the inclusion criteria. Seventeen were cluster-randomised trials, with a majority investigating interventions aimed at improving processes compared with usual care. Sample sizes varied between 6 and 606 clusters and 168 and 7807 participants. The most frequent methodological problem was risk of selection bias due to recruitment of individuals after randomisation of clusters. Effects of interventions over usual care were mostly small (SMD <0.3). Sixteen trials randomising individual participants addressed a variety of treatment and educational interventions. Sample sizes varied between 20 and 1620 participants. The methodological quality of the trials was highly variable. Again, effects of experimental interventions over controls were mostly small., Conclusions: Despite limited funding, German university institutes of general practice or family medicine are increasingly performing randomised trials. Cluster-randomised trials on practice improvement are a focus, but problems with allocation concealment are frequent.

Background: Homeopathy is often sought by patients with depression. In classical homeopathy, the treatment consists of two main elements: the case history and the prescription of an individually selected homeopathic remedy. Previous data suggest that individualized homeopathic Q-potencies were not inferior to the antidepressant fluoxetine in a sample of patients with moderate to severe depression. However, the question remains whether individualized homeopathic Q-potencies and/or the type of the homeopathic case history have a specific therapeutical effect in acute depression as this has not yet been investigated. The study aims to assess the two components of individualized homeopathic treatment for acute depression, i.e., to investigate the specific effect of individualized Q-potencies versus placebo and to investigate the effect of different approaches to the homeopathic case history., Methods/design: A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2 x 2 factorial design with a six-week study duration per patient will be performed. 228 patients diagnosed with major depression (moderate episode) by a psychiatrist will be included. The primary endpoint is the total score on the 17-item Hamilton Depression Rating Scale after six weeks. Secondary end points are: Hamilton Depression Rating Scale total score after two and four weeks; response and remission rates, Beck Depression inventory total score, quality of life and safety at two, four and six weeks. Statistical analyses will be by intention-to-treat. The main endpoint will be analysed by a two-factorial analysis of covariance. Within this model generalized estimation equations will be used to estimate differences between verum and placebo, and between both types of case history., Discussion: For the first time this study evaluates both the specific effect of homeopathic medicines and of a homeopathic case taking in patients with depression. It is an attempt to deal with the challenges of homeopathic research and the results might be useful information in the current discussion about the evidence on homeopathy, Trial Registration: ClinicalTrials.gov: NCT01178255.

Background: The purpose of clinical trials of acupuncture is to help clinicians and patients make decisions about treatment. Yet this is not straightforward: some trials report acupuncture to be superior to sham (placebo) acupuncture while others show evidence that acupuncture is superior to usual care but not sham, and still others conclude that acupuncture is no better than usual care. Meta-analyses of these trials tend to come to somewhat indeterminate conclusions. This appears to be because, until recently, acupuncture research was dominated by small trials of questionable quality. The Acupuncture Trialists' Collaboration, a group of trialists, statisticians and other researchers, was established to synthesize patient-level data from several recently published large, high-quality trials., Methods: There are three distinct phases to the Acupuncture Trialists Collaboration: a systematic review to identify eligible studies; collation and harmonization of raw data; statistical analysis. To be eligible, trials must have unambiguous allocation concealment. Eligible pain conditions are osteoarthritis; chronic headache (tension or migraine headache); shoulder pain; and non-specific back or neck pain. Once received, patient-level data will undergo quality checks and the results of prior publications will be replicated. The primary analysis will be to determine the effect size of acupuncture. Each trial will be evaluated by analysis of covariance with the principal endpoint as the dependent variable and, as covariates, the baseline score for the principal endpoint and the variables used to stratify randomization. The effect size for acupuncture from each trial--that is, the coefficient and standard error from the analysis of covariance--will then be entered into a meta-analysis. We will compute effect sizes separately for comparisons of acupuncture with sham acupuncture, and acupuncture with no acupuncture control for each pain condition. Other analyses will investigate the impact of different sham techniques, styles of acupuncture or frequency and duration of treatment sessions., Discussion: Individual patient data meta-analysis of high-quality trials will provide the most reliable basis for treatment decisions about acupuncture. Above all, however, we hope that our approach can serve as a model for future studies in acupuncture and other complementary therapies.