Conflicts of interest in randomised controlled surgical trials: systematic review and qualitative and quantitative analysis.
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SUBMITTER: Probst P
PROVIDER: S-EPMC6753986 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo characterise and analyse the experiences of trial researchers of if and how conflicts of interest had unduly influenced clinical trials they had worked on, what management strategies they had used to minimise any potential influence, and their experiences and views on conflicts of interest more generally.DesignQualitative interview study.ParticipantsTrial researchers who had participated in at least 10 clinical trials with methodological or statistical expertise. Researchers differed by geographical location, educational background, and experience with different types of funders. Interviewees were identified by searches on Web of Science and snowball sampling. 52 trial researchers were approached by email; 20 agreed to be interviewed.SettingInterviews conducted by telephone, recorded, transcribed verbatim, imported to NVivo 12, and analysed by systematic text condensation. Semistructured interviews focused on financial and non-financial conflicts of interest.ResultsThe interviewees had participated in a median of 37.5 trials and were mainly male physicians who had experience with commercial and non-commercial trial funders. Two predefined themes (influence of conflicts of interest and management strategies) and two additional themes (definition and reporting of conflicts of interest) emerged. Examples of perceived influence of conflicts of interest were: choice of inferior comparator, manipulation of the randomisation process, prematurely stopping the trials, fabrication of data, blocking access to data, and spin (eg, overly favourable interpretation of the results). Examples of strategies to manage conflicts of interest were: disclosure procedures, exclusion of the funder from design and analysis, independent committees, contracts ensuring complete access to the data, and no restriction by the funder on analysis and reporting. Interviewees used different definitions or thresholds for what they considered to be conflicts of interest, and they described different criteria for when to report them. Some interviewees considered non-commercial financial conflicts of interest (eg, funding of trials by governmental health agencies with a political agenda) to be equally or more important than commercial financial conflicts of interest (eg, funding by drug and device companies), but more challenging to report and manage.ConclusionThis study described how trial researchers perceive conflicts of interest unduly influencing clinical trials they had worked on, and the management strategies they used to prevent these influences. The results indicated considerable variability in researchers' understanding of what conflicts of interest are and when they should be reported.
| S-EPMC7590918 | biostudies-literature
Project description:OBJECTIVES:To find evidence, either corroborating or refuting, for many persisting beliefs regarding the feasibility of carrying out surgical randomised controlled trials with a placebo arm, with emphasis on the challenges related to recruitment, funding, anaesthesia or blinding. DESIGN:Systematic review. DATA SOURCES AND STUDY SELECTION:The analysis involved studies published between 1959 and 2014 that were identified during an earlier systematic review of benefits and harms of placebo-controlled surgical trials published in 2014. RESULTS:63 trials were included in the review. The main problem reported in many trials was a very slow recruitment rate, mainly due to the difficulty in finding eligible patients. Existing placebo trials were funded equally often from commercial and non-commercial sources. General anaesthesia or sedation was used in 41% of studies. Among the reviewed trials, 81% were double-blinded, and 19% were single-blinded. Across the reviewed trials, 96% (range 50-100%) of randomised patients completed the study. The withdrawal rate during the study was similar in the surgical and in the placebo groups. CONCLUSIONS:This review demonstrated that placebo-controlled surgical trials are feasible, at least for procedures with a lower level of invasiveness, but also that recruitment is difficult. Many of the presumed challenges to undertaking such trials, for example, funding, anaesthesia or blinding of patients and assessors, were not reported as obstacles to completion in any of the reviewed trials.
| S-EPMC4800115 | biostudies-literature
Project description:To develop an empirically based framework of the aspects of randomised controlled trials addressed by qualitative research. Systematic mapping review of qualitative research undertaken with randomised controlled trials and published in peer-reviewed journals. MEDLINE, PreMEDLINE, EMBASE, the Cochrane Library, Health Technology Assessment, PsycINFO, CINAHL, British Nursing Index, Social Sciences Citation Index and ASSIA. Articles reporting qualitative research undertaken with trials published between 2008 and September 2010; health research, reported in English. 296 articles met the inclusion criteria. Articles focused on 22 aspects of the trial within five broad categories. Some articles focused on more than one aspect of the trial, totalling 356 examples. The qualitative research focused on the intervention being trialled (71%, 254/356); the design, process and conduct of the trial (15%, 54/356); the outcomes of the trial (1%, 5/356); the measures used in the trial (3%, 10/356); and the target condition for the trial (9%, 33/356). A minority of the qualitative research was undertaken at the pretrial stage (28%, 82/296). The value of the qualitative research to the trial itself was not always made explicit within the articles. The potential value included optimising the intervention and trial conduct, facilitating interpretation of the trial findings, helping trialists to be sensitive to the human beings involved in trials, and saving money by steering researchers towards interventions more likely to be effective in future trials. A large amount of qualitative research undertaken with specific trials has been published, addressing a wide range of aspects of trials, with the potential to improve the endeavour of generating evidence of effectiveness of health interventions. Researchers can increase the impact of this work on trials by undertaking more of it at the pretrial stage and being explicit within their articles about the learning for trials and evidence-based practice.
| S-EPMC3669723 | biostudies-literature
Project description:ObjectiveThis study aimed to systematically review the effects of declared and undeclared conflicts of interest on randomised controlled trials (RCTs) of patient blood management (PBM) interventions.DesignWe performed a secondary analysis of a recently published meta-analysis of RCTs evaluating five common PBM interventions in patients undergoing major surgery.Data sourcesThe databases searched by the original systematic reviews were searched using subject headings and Medical Subject Headings terms according to search strategies from the final search time-points until 1 June 2019.Eligibility criteriaRCTs on PBM irrespective of blinding, language, date of publication and sample size were included. Abstracts and unpublished trials were excluded. Conflicts of interest were defined as sponsorship, funding or authorship by industry, professional PBM advocacy groups or blood services.Data extraction and synthesisThree independent reviewers extracted the data and assessed the risk of bias. Pooled treatment effect estimates were reported as risk ratios (RRs) or standardised mean difference with 95% CIs. Heterogeneity was quantified using the I2 statistic.ResultsThree hundred and eighty-nine RCTs totalling 53 635 participants were included. Thirty-two trials (8%) were considered free from important sources of bias. There was reporting bias favouring PBM interventions on transfusion across all analyses. In trials with no declared author conflicts of interest, the treatment effect on mortality was RR 1.12 (0.86 to 1.45). In trials where author conflicts of interest were declared, the treatment effect on mortality was RR 0.84 (0.69 to 1.03), with significant reporting bias favouring PBM interventions. Trials with declared conflicts linked to professional PBM advocacy groups (five studies, n=977 patients) reported statistically significant reductions in mortality RR 0.40 (0.17 to 0.92), unlike other groups.ConclusionsLow certainty of the evidence that guides PBM implementation is confounded by evidence of reporting bias, and the effects of declared and undeclared conflicts of interest, favouring PBM on important trial outcomes.
| S-EPMC9389106 | biostudies-literature
Project description:PurposeRandomised controlled trials (RCTs) are considered the gold standard for evaluating the efficacy of an intervention. However, previous research has shown that RCTs in several surgical specialities are poorly reported, making it difficult to ascertain if various biases have been appropriately minimised. This systematic review assesses the reporting quality of surgical head and neck cancer RCTs.MethodsA literature search of PubMed and Embase was performed. Papers were included if they reported RCTs which assessed a surgical technique used to treat or diagnose head and neck cancer published during or after 2011. The CONSORT 2010 checklist was used to evaluate the reporting quality of these trials.Results41 papers were included. The mean CONSORT score was 16.5/25 (66% adherence) and the scores ranged from 7.5 (30%) to 25. The most common omissions were full trial protocol (found in 14.6%), participant recruitment method (22%) and effect size with a precision estimate for all outcome measures (29.3%). The full design and implementation of the randomisation methods were reported in 6 (14.6%). Papers published in journals which endorsed CONSORT had significantly higher scores (p = 0.02) and the journal impact factor was significantly correlated with CONSORT score (p = 0.01).ConclusionWe have identified several pieces of information that are underreported in surgical head and neck cancer RCTs. These omissions make understanding and comparing the methodologies and conclusions of RCTs more difficult. The endorsement of CONSORT by journals improved adherence, suggesting that wider adoption of the checklist may improve reporting.
| S-EPMC8486722 | biostudies-literature
Project description:BackgroundThe reporting of randomised controlled non-inferiority (NI) drug trials is poor with less than 50% of published trials reporting a justification of the NI margin. This is despite the introduction of the Consolidated Standards of Reporting Trials (CONSORT) extension on reporting of NI and equivalence in randomised trials. It is critical to set the appropriate NI margin as this choice dictates the conclusions of the trial. Methods to estimate the margin are heterogeneous but generally based on clinical judgement and statistical reasoning, and hence tailored to each clinical situation. Yet an appraisal of NI in clinical trials has not been undertaken. Therefore the aim of this systematic review is to assess the reporting and methodological quality of defining the NI margin. Surgical NI trials have been chosen as our prototype to assess this.MethodsWe will conduct a systematic review of published randomised controlled trials in abdominal surgery that use an NI design. Key eligibility criteria will be: surgical intervention in at least one trial arm; adult patients and a sample size of 100 or more. Ovid MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be searched from inception until the date of the search. Identified studies will be assessed for reporting according to the CONSORT recommendations. The outcomes are the description of the methods for defining the NI margin, and the robustness of the NI margin estimation. The latter will be based on simulations using alternative assumptions for model parameters. The results of the simulation will be compared with the trial authors' conclusions.Anticipated resultsThe review will describe and appraise the design and reporting of surgical NI trials including shortcomings thereof and allow a comparison with pharmaceutical trials. These findings will inform researchers on the appropriate design and pitfalls when conducting surgical randomised controlled trials with an NI design and promote thorough and standardised reporting of study findings.Ethics and disseminationEthical approval is not required and any changes to the protocol will be communicated via the registration platform. The final manuscript will be submitted to a journal for publication and the findings will be disseminated through conference presentations to inform researchers and the public.
| S-EPMC11344494 | biostudies-literature
Project description:It is common to undertake qualitative research alongside randomised controlled trials (RCTs) when evaluating complex interventions. Researchers tend to analyse these datasets one by one and then consider their findings separately within the discussion section of the final report, rarely integrating quantitative and qualitative data or findings, and missing opportunities to combine data in order to add rigour, enabling thorough and more complete analysis, provide credibility to results, and generate further important insights about the intervention under evaluation. This paper reports on a 2 day expert meeting funded by the United Kingdom Medical Research Council Hubs for Trials Methodology Research with the aims to identify current strengths and weaknesses in the integration of quantitative and qualitative methods in clinical trials, establish the next steps required to provide the trials community with guidance on the integration of mixed methods in RCTs and set-up a network of individuals, groups and organisations willing to collaborate on related methodological activity. We summarise integration techniques and go beyond previous publications by highlighting the potential value of integration using three examples that are specific to RCTs. We suggest that applying mixed methods integration techniques to data or findings from studies involving both RCTs and qualitative research can yield insights that might be useful for understanding variation in outcomes, the mechanism by which interventions have an impact, and identifying ways of tailoring therapy to patient preference and type. Given a general lack of examples and knowledge of these techniques, researchers and funders will need future guidance on how to undertake and appraise them.
| S-EPMC6886933 | biostudies-literature
Project description:ObjectiveTo systematically evaluate the prevalence of disclosed and undisclosed financial conflicts of interest (FCOI) among clinical practice guidelines (CPGs).MethodsIn this systematic review, we ascertained the prevalence and types of FCOI for CPGs from January 1, 1980, to March 3, 2019. The primary outcome was the prevalence of FCOI among authors of CPGs. FCOI disclosures were compared between medical subspecialties and societies producing CPGs.ResultsAmong the 37 studies including 14,764 total guideline authors, 45% had at least one FCOI. The prevalence of FCOI per study ranged from 6% to 100%. More authors had FCOI involving general payments (39%) compared with research payments (29%). Oncology, neurology, and gastroenterology had the highest prevalence of FCOI compared with other medical specialties. Among the 8 studies that included the monetary values in US dollars of FCOI, average payments per author ranged from $578 to $242,300. Among the 10 studies that included data on undisclosed FCOI, 32% of authors had undisclosed industry payments.ConclusionThere are numerous FCOI among authors of CPGs, many of which are undisclosed. Our study found a significant difference in FCOI prevalence based on types of FCOI and CPG sponsor society. Additional research is required to quantify the implications of FCOI on clinical judgment and patient care.
| S-EPMC8105509 | biostudies-literature
Project description:To explore conflicts of interest (COI) and their reporting in systematic reviews of psychological therapies, and to evaluate spin in the conclusions of the reviews.MEDLINE and PsycINFO databases were searched for systematic reviews published between 2010 and 2013 that assessed effects of psychological therapies for anxiety, depressive or personality disorders, and included at least one randomised controlled trial. Required COI disclosure by journal, disclosed COI by review authors, and the inclusion of own primary studies by review authors were extracted. Researcher allegiance, that is, that researchers concluded favourably about the interventions they have studied, as well as spin, that is, differences between results and conclusions of the reviews, were rated by 2 independent raters.936 references were retrieved, 95 reviews fulfilled eligibility criteria. 59 compared psychological therapies with other forms of psychological therapies, and 36 psychological therapies with pharmacological interventions. Financial, non-financial, and personal COI were disclosed in 22, 4 and 1 review, respectively. 2 of 86 own primary studies of review authors included in 34 reviews were disclosed by review authors. In 15 of the reviews, authors showed an allegiance effect to the evaluated psychological therapy that was never disclosed. Spin in review conclusions was found in 27 of 95 reviews. Reviews with a conclusion in favour of psychological therapies (vs pharmacological interventions) were at high risk for a spin in conclusions (OR=8.31 (1.41 to 49.05)). Spin was related in trend to the inclusion of own primary studies in the systematic review (OR=2.08 (CI 0.83 to 5.18) p=0.11) and researcher allegiance (OR=2.63 (0.84 to 8.16) p=0.16).Non-financial COI, especially the inclusion of own primary studies into reviews and researcher allegiance, are frequently seen in systematic reviews of psychological therapies and need more transparency and better management.
| S-EPMC4853969 | biostudies-other
Project description:OBJECTIVE:Randomised controlled trials (RCT) are the gold standard to provide unbiased data. However, when patients have a treatment preference, randomisation may influence participation and outcomes (eg, external and internal validity). The aim of this study was to assess the influence of patients' preference in RCTs by analysing partially randomised patient preference trials (RPPT); an RCT and preference cohort combined. DESIGN:Systematic review and meta-analyses. DATA SOURCES:MEDLINE, Embase, PsycINFO and the Cochrane Library. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:RPPTs published between January 2005 and October 2018 reporting on allocation of patients to randomised and preference cohorts were included. DATA EXTRACTION AND SYNTHESIS:Two independent reviewers extracted data. The main outcomes were the difference in external validity (participation and baseline characteristics) and internal validity (lost to follow-up, crossover and the primary outcome) between the randomised and the preference cohort within each RPPT, compared in a meta-regression using a Wald test. Risk of bias was not assessed, as no quality assessment for RPPTs has yet been developed. RESULTS:In total, 117 of 3734 identified articles met screening criteria and 44 were eligible (24 873 patients). The participation rate in RPPTs was >95% in 14 trials (range: 48%-100%) and the randomisation refusal rate was >50% in 26 trials (range: 19%-99%). Higher education, female, older age, race and prior experience with one treatment arm were characteristics of patients declining randomisation. The lost to follow-up and cross-over rate were significantly higher in the randomised cohort compared with the preference cohort. Following the meta-analysis, the reported primary outcomes were comparable between both cohorts of the RPPTs, mean difference 0.093 (95% CI -0.178 to 0.364, p=0.502). CONCLUSIONS:Patients' preference led to a substantial proportion of a specific patient group refusing randomisation, while it did not influence the primary outcome within an RPPT. Therefore, RPPTs could increase external validity without compromising the internal validity compared with RCTs. PROSPERO REGISTRATION NUMBER:CRD42019094438.
| S-EPMC6797441 | biostudies-other