Reporting of clinical trials: a review of research funders' guidelines

BACKGROUND: Randomised controlled trials (RCTs) represent the gold standard methodological design to evaluate the effectiveness of an intervention in humans but they are subject to bias, including study publication bias and outcome reporting bias. National and international organisations and charities give recommendations for good research practice in relation to RCTs but to date no review of these guidelines has been undertaken with respect to reporting bias. METHODS: National and international organisations and UK based charities listed on the Association for Medical Research Charities website were contacted in 2007; they were considered eligible for this review if they funded RCTs. Guidelines were obtained and assessed in relation to what was written about trial registration, protocol adherence and trial publication. It was also noted whether any monitoring against these guidelines was undertaken. This information was necessary to discover how much guidance researchers are given on the publication of results, in order to prevent study publication bias and outcome reporting bias. RESULTS: Seventeen organisations and 56 charities were eligible of 140 surveyed for this review, although there was no response from 12. Trial registration, protocol adherence, trial publication and monitoring against the guidelines were often explicitly discussed or implicitly referred too. However, only eleven of these organisations or charities mentioned the publication of negative as well as positive outcomes and just three of the organisations specifically stated that the statistical analysis plan should be strictly adhered to and all changes should be reported. CONCLUSION: Our review indicates that there is a need to provide more detailed guidance for those conducting and reporting clinical trials to help prevent the selective reporting of results. Statements found in the guidelines generally refer to publication bias rather than outcome reporting bias. Current guidelines need to be updated and include the statement that all primary and secondary outcomes prespecified in the protocol should be fully reported and should not be selected for inclusion in the final report based on their results

Relation between awareness of circulatory disorders and smoking in a general population health examination

BACKGROUND: Little is known about proportions of smokers who maintain smoking after they are aware of a circulatory disorder. The goal was to analyze the extent to which the number of circulatory disorders may be related to being a current smoker. METHODS: Cross-sectional survey study with a probability sample of residents in Germany investigated in health examination centers. Questionnaire data of 3,778 ever smoking participants aged 18 – 79 were used, questions included whether the respondent had ever had hypertension, myocardial infarction, other coronary artery disease, heart failure, stroke, other cerebrovascular disease, peripheral vascular disease, and venous thrombosis. Logistic regression was calculated for circulatory disorders and their number with current smoking as the dependent variable, and odds ratios (OR) are presented adjusted for physician contact, inpatient treatment, smoking cessation counseling, heavy smoking, exercise, overweight and obesity, school education, sex and age. RESULTS: Among ever smokers who had 1 circulatory disorder, 52.1 % were current smokers and among those who reported that they had 3 or more circulatory disorders 28.0 % were current smokers at the time of the interview. The adjusted odds of being a current smoker were lower for individuals who had ever smoked in life and had 2 or more central circulatory disorders, such as myocardial infarction, heart failure or stroke, than for ever smokers without central circulatory disorder (2 or more disorders: adjusted OR 0.6, 95 % confidence interval, CI, 0.4 to 0.8). CONCLUSION: Among those with central circulatory disorders, there is a substantial portion of individuals who smoke despite their disease. The data suggest that only a portion of smokers among the general population seems to be discouraged from smoking by circulatory disorders or its accompanying cognitive or emotional processes

Are old-old patients with major depression more likely to relapse than young-old patients during continuation treatment with escitalopram?

<p>Abstract</p> <p>Background</p> <p>Escitalopram has shown efficacy and tolerability in the prevention of relapse in elderly patients with major depressive disorder (MDD). This <it>post-hoc </it>analysis compared time to relapse for <it>young-old </it>patients (n = 197) to that for <it>old-old </it>patients (n = 108).</p> <p>Method</p> <p>Relapse prevention: after 12-weeks open-label treatment, remitters (MADRS ≤12) were randomised to double-blind treatment with escitalopram or placebo and followed over 24-weeks. Patients were outpatients with MDD from 46 European centers aged ≥75 years (<it>old-old</it>) or 65-74 years of age (<it>young-old</it>), treated with escitalopram 10-20mg/day. Efficacy was assessed using the Montgomery Åsberg Depression Rating Scale (MADRS).</p> <p>Results</p> <p>After open-label escitalopram treatment, a similar proportion of <it>young-old </it>patients (78%) and <it>old-old </it>patients (72%) achieved remission. In the analysis of time to relapse based on the Cox model (proportional hazards regression), with treatment and age group as covariates, the hazard ratio was 4.4 for placebo <it>versus </it>escitalopram (χ²-test, df = 1, χ²= 22.5, p < 0.001), whereas the effect of age was not significant, with a hazard ratio of 1.2 for <it>old-old </it>versus <it>young-old </it>(χ²-test, df = 1, χ²= 0.41, p = 0.520). Escitalopram was well tolerated in both age groups with adverse events reported by 53.1% of <it>young-old </it>patients and 58.3% of <it>old-old </it>patients. There was no significant difference in withdrawal rates due to AEs between age groups (χ²-test, χ²= 1.669, df = 1, p = 0.196).</p> <p>Conclusions</p> <p><it>Young-old </it>and <it>old-old </it>patients with MDD had comparable rates of remission after open-label escitalopram, and both age groups had much lower rates of relapse on escitalopram than on placebo.</p

Acute atomoxetine treatment of younger and older children with ADHD: A meta-analysis of tolerability and efficacy

<p>Abstract</p> <p>Background</p> <p>Atomoxetine is FDA-approved as a treatment of attention-deficit/hyperactivity disorder (ADHD) in patients aged 6 years to adult. Among pediatric clinical trials of atomoxetine to date, six with a randomized, double-blind, placebo-controlled design were used in this meta-analysis. The purpose of this article is to describe and compare the treatment response and tolerability of atomoxetine between younger children (6–7 years) and older children (8–12 years) with ADHD, as reported in these six acute treatment trials.</p> <p>Methods</p> <p>Data from six clinical trials of 6–9 weeks duration were pooled, yielding 280 subjects, ages 6–7 years, and 860 subjects, ages 8–12 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-diagnosed ADHD. Efficacy was analyzed using the ADHD Rating Scale-IV (ADHD-RS), Conners' Parent Rating Scale-revised (CPRS-R:S), and the Clinical Global Impression of ADHD Severity (CGI-ADHD-S).</p> <p>Results</p> <p>Atomoxetine was superior to placebo in both age categories for mean (SD) change in ADHD-RS total, total T, and subscale scores; 3 CPRS-R:S subscales; and CGI-ADHD-S from baseline. Although there were no significant treatment differentials between the age groups for these efficacy measures, the age groups themselves, regardless of treatment, were significantly different for ADHD-RS total (younger: ATX = -14.2 [13.8], PBO = -4.6 [10.4]; older: ATX = -15.4 [13.2], PBO = -7.3 [12.0]; p = .001), total T (younger: ATX = -15.2 [14.8], PBO = -4.9 [11.2]; older: ATX = -16.4 [14.6], PBO = -7.9 [13.1]; p = .003), and subscale scores (Inattentive: younger: ATX = -7.2 [7.5], PBO = -2.4 [5.7]; older: ATX = -8.0 [7.4], PBO = -3.9 [6.7]; p = .043; Hyperactive/Impulsive: younger: ATX = -7.0 [7.2], PBO = -2.1 [5.4]; older: ATX = -7.3 [7.0], PBO = -3.4 [6.3]; p < .001), as well as the CGI-ADHD-S score (younger: ATX = -1.2 [1.3], PBO = -0.5 [0.9]; older: ATX = -1.4 [1.3], PBO = -0.7 [1.1]; p = .010). Although few subjects discontinued from either age group due to adverse events, a significant treatment-by-age-group interaction was observed for abdominal pain (younger: ATX = 19%, PBO = 6%; older: ATX = 15%, PBO = 13%; p = .044), vomiting (younger: ATX = 14%, PBO = 2%; older: ATX = 9%, PBO = 6%; p = .053), cough (younger: ATX = 10%, PBO = 6%; older: ATX = 3%, PBO = 9%; p = .007), and pyrexia (younger: ATX = 5%, PBO = 2%; older: ATX = 3%, PBO = 5%; p = .058).</p> <p>Conclusion</p> <p>Atomoxetine is an effective and generally well-tolerated treatment of ADHD in both younger and older children as assessed by three recognized measures of symptoms in six controlled clinical trials.</p> <p>Trial Registration</p> <p>Not Applicable.</p

Health research ethics in malaria vector trials in Africa

Malaria mosquito research in Africa as elsewhere is just over a century old. Early trials for development of mosquito control tools were driven by colonial enterprises and war efforts; they were, therefore, tested in military or colonial settings. The failure of those tools and environmental concerns, coupled with the desperate need for integrated malaria control strategies, has necessitated the development of new malaria mosquito control tools, which are to be tested on humans, their environment and mosquito habitats. Ethical concerns start with phase 2 trials, which pose limited ethical dilemmas. Phase 3 trials, which are undertaken on vulnerable civilian populations, pose ethical dilemmas ranging from individual to community concerns. It is argued that such trials must abide by established ethical principles especially safety, which is mainly enshrined in the principle of non-maleficence. As there is total lack of experience with many of the promising candidate tools (eg genetically modified mosquitoes, entomopathogenic fungi, and biocontrol agents), great caution must be exercised before they are introduced in the field. Since malaria vector trials, especially phase 3 are intrusive and in large populations, individual and community respect is mandatory, and must give great priority to community engagement. It is concluded that new tools must be safe, beneficial, efficacious, effective, and acceptable to large populations in the short and long-term, and that research benefits should be equitably distributed to all who bear the brunt of the research burdens. It is further concluded that individual and institutional capacity strengthening should be provided, in order to undertake essential research, carry out scientific and ethical review, and establish competent regulatory frameworks

Effectiveness of second-generation antipsychotics: a naturalistic, randomized comparison of olanzapine, quetiapine, risperidone, and ziprasidone

<p>Abstract</p> <p>Background</p> <p>No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes.</p> <p>Methods</p> <p>Patients ≥ 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years.</p> <p>Results</p> <p>A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups.</p> <p>Conclusions</p> <p>Quetiapine appears to be a good starting drug candidate in this sample of patients admitted to hospital for symptoms of psychosis.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID; URL: <url>http://www.clinicaltrials.gov/</url>: NCT00932529</p

An occupational justice perspective on playing football and living with mental distress

© 2020 The Author(s). Physical inactivity is a global public health priority, yet people living with a disability or long-term health condition, such as those who experience mental distress, continue to face inequalities and barriers to participation in sport and physical activity. These inequalities are considered an occupational injustice, in terms of participation in health enhancing occupations being restricted for these groups of people, despite them wanting to be more active. This study aimed to gain an in-depth understanding of the nature and value of participating in a UK based community football project, for people with experience of mental distress. Twenty-three people took part in this first strand of a larger participatory action research study, which used the World Café as a method for structuring and recording conversations. Data from the three World Café events were analysed collectively and thematically. The study’s findings reveal tensions, nuances, and subtleties that exist in relation to the reciprocal relationship between playing football and people’s health and well-being. The complexity of enabling participation in sport and physical activity amongst marginalised groups, such as people with experience of mental distress, is highlighted.Elizabeth Casson Trus