Factors relating to nonpublication and publication bias in clinical trials in Canada: A qualitative interview study.

AIMS: This study aims to understand factors contributing to nonpublication and publication bias in clinical trials in Canada. METHODS: Qualitative interviews were conducted between March 2019 and April 2021 with 34 participants from the Canadian provinces of Alberta, British Columbia and Ontario, including 17 clinical trial investigators, 1 clinical research coordinator, 3 research administrators, 3 research ethics board members and 10 clinical trial participants. We conducted a thematic analysis involving coding of interview transcripts and memo-writing to identify key themes. RESULTS: Several factors contribute to nonpublication and publication bias in clinical trial research. A core theme was that reporting practices are shaped by incentives within the research system taht favour publication of positive over negative trials. Investigators are discouraged from reporting by experiences or perceptions of difficulty in publishing negative findings but rewarded for publishing positive findings in various ways. Trial investigators more strongly associated positive clinical trials than negative trials with opportunities for industry and nonindustry funding and with academic promotion, bonuses and recognition. Research institutions and ethics boards tended to lack well-resourced, proactive policies and practices to ensure trial findings are reported in registries or journals. CONCLUSION: Clinical trial reporting practices in Canada are shaped by incentives favouring reporting of positive over negative trials, such as funding opportunities and academic promotion, bonuses and recognition. Research institutions could help change incentives by adopting performance metrics that emphasize full reporting of results in journals or registries.

The publication of impaired doctors' identity by Australian and New Zealand tribunals: law, practice, and reform.

For doctors with mental health or substance use disorders, publication of their name and sensitive medical history in disciplinary decisions may adversely impact their health and may reinforce barriers to accessing early support and treatment. This article challenges the view that naming impaired doctors or disclosing the intimate details of their medical condition in disciplinary decisions always serves the public interest in open justice. We analysed and compared the approach of Australian and New Zealand health tribunals to granting orders that suppress the name and/or medical history of impaired doctors. This revealed that Australian tribunals are less likely to grant non-publication orders compared to New Zealand, despite shared common law history and similar medical regulatory frameworks. We argue that Australian tribunals could be more circumspect when dealing with sensitive information in published decisions, especially where such information does not directly form a basis for the decision reached. This could occur without compromising public protection or the underlying goals of open justice. Finally, we argue that a greater distinction should be made between those aspects of decisions that deal with conduct allegations, where full details should be published, and those that deal with impairment allegations, where only limited information should be disclosed.

Publication of neurology clinical trials registered with clinical trial registry of India: A cross-sectional study.

OBJECTIVES: Unbiased and full disclosure of trial results is vital to evidence-based medicine. Non-publication and selective publication leads to publication bias and unrealistic risk-benefit ratio. In the present study, we aim to determine the publication rate of clinical trials related to neurology registered with the Clinical Trial Registry of India (CTRI), compare the characteristics of published and unpublished trials, and evaluate the adherence of investigators to ethics-approved criteria and outcomes. MATERIALS AND METHODS: A cross-sectional search using the keyword "neurology" was carried out in CTRI registry. Two independent investigators searched Pubmed, Medline, Scopus, and Google Scholar for published manuscripts. The final literature search occurred in November 2021. RESULTS: Out of 325 trials, 102 trials were published (31.4%). Ninety-one trials were beyond 3 years of expected time of trial completion and were still unpublished. Randomized trials had a slightly higher publication rate than non-randomized ones (56% vs. 46%, p = .223); however the difference was not statistically significant. Majority of trials sponsored by pharmaceutical companies were not published, while majority of those sponsored by non-pharmaceutical institutions were published (34.5% vs. 69.3%, p < .001). Feedback to CTRI about trial status was particularly poor (31.5% - informed vs. 68.5% - not informed, p < .001). 52 (50.9%) and 65 (63.7%) of the 102 published trials had changed the registered inclusion and exclusion criteria, respectively, in the CTRI registry compared to those in the published manuscript. In 29 (28.3%) of the 102 trials, the primary outcome did not match with that registered in the CTRI and in 73 (57.8%) trials, the secondary outcomes did not match. CONCLUSION: A large proportion of neurology registered trials are still unpublished, with a majority of pharmaceutical company-sponsored trials not being published. There is scope for improving the provisions in CTRI for enlisting trial results, that may prevent publication bias and also ensure the investigators adhere to the pre-specified ethics approved trial procedures and outcomes.

Delays in reporting and publishing trial results during pandemics: cross sectional analysis of 2009 H1N1, 2014 Ebola, and 2016 Zika clinical trials.

BACKGROUND: Pandemic events often trigger a surge of clinical trial activity aimed at rapidly evaluating therapeutic or preventative interventions. Ensuring rapid public access to the complete and unbiased trial record is particularly critical for pandemic research given the urgent associated public health needs. The World Health Organization (WHO) established standards requiring posting of results to a registry within 12 months of trial completion and publication in a peer reviewed journal within 24 months of completion, though compliance with these requirements among pandemic trials is unknown. METHODS: This cross-sectional analysis characterizes availability of results in trial registries and publications among registered trials performed during the 2009 H1N1 influenza, 2014 Ebola, and 2016 Zika pandemics. We searched trial registries to identify clinical trials testing interventions related to these pandemics, and determined the time elapsed between trial completion and availability of results in the registry. We also performed a comprehensive search of MEDLINE via PubMed, Google Scholar, and EMBASE to identify corresponding peer reviewed publications. The primary outcome was the compliance with either of the WHO's established standards for sharing clinical trial results. Secondary outcomes included compliance with both standards, and assessing the time elapsed between trial completion and public availability of results. RESULTS: Three hundred thirty-three trials met eligibility criteria, including 261 H1N1 influenza trials, 60 Ebola trials, and 12 Zika trials. Of these, 139 (42%) either had results available in the trial registry within 12 months of study completion or had results available in a peer-reviewed publication within 24 months. Five trials (2%) met both standards. No results were available in either a registry or publication for 59 trials (18%). Among trials with registered results, a median of 42 months (IQR 16-76 months) elapsed between trial completion and results posting. For published trials, the median elapsed time between completion and publication was 21 months (IQR 9-34 months). Results were available within 24 months of study completion in either the trial registry or a peer reviewed publication for 166 trials (50%). CONCLUSIONS: Very few trials performed during prior pandemic events met established standards for the timely public dissemination of trial results.

Low dissemination rates, non-transparency of trial premature cessation and late registration in child mental health: observational study of registered interventional trials.

The aim of this observational study was to explore trial premature cessation, non-publication and trial registration time in child mental health. Data were extracted for "closed" trials in Clinicaltrials.gov registry and European Union Clinical Trial Register (EUCTR) and corresponding publications of completed trials indexed in three data bases (PubMed, Scopus and Google Scholar). We restricted the extraction to the 'Behaviours and Mental Disorders' category and participants' age of 0-17 years. Outcome measures were trial completion, results reporting within a year after the trial completion, publishing an article in a peer-reviewed journal within an average time to publish (729 days), and registration time. The number of EUCTR trials was relatively small (n = 35) and with many inconsistencies. Out of 827 "closed" trials extracted from ClinicalTrials.gov, 69% were completed, 24.2% of prematurely ceased trials did not report reasons for early termination, 12.2% of the completed trials had results reported within a year, and 29.3% had an article published within 24 months after completion. Middle-sized (100-499 participants) and behavioural trials had higher chances of being successfully completed. Middle-sized and industry-funded trials were associated with results reporting. Chances for publishing an article were lower for industry-funded trials. Industry funding and drug interventions were related to timely registration. Large sample and non-industry funding were related to retrospective registration, which was recorded more often in recent years than before (we observed trials registered from 2002 until 2017). This study found low dissemination rates in the field of child mental health, with worrying under-reporting of premature termination causes. These findings indicate that more children are being subjected to unnecessary risk that comes with trial participation.

An observational analysis of discontinuation and non-publication of osteoarthritis trials.

OBJECTIVE: Discontinuation and nonpublication are causes for concern in highly funded research areas of prevalent medical conditions. The aim of our study is to evaluate the rate of discontinuation and nonpublication in osteoarthritis randomized controlled clinical trials. DESIGN: We used the ClinicalTrials.gov advanced search using the keyword "osteoarthritis" for phase 3 or phase 4 clinical trials in adults. Two investigators then independently screened the search results by registered title, condition, study design, and completion date. We then performed a systematic search to determine the publication status of the study. RESULTS: Our final analysis included 273 studies. Our analysis of these studies included 243 (89%) completed and 30 (11%) discontinued trials. A total of 121,307 (92%) and 10,368 (8%) patients participated in completed and discontinued trials, respectively. Following our searches of PubMed, Embase, and Google Scholar, we identified 67 of the 243 (27.6%) studies as completed but having not reached publication in manuscript form. CONCLUSIONS: If discontinuation and non-publication rates in osteoarthritis trials continue to be sub-optimal, already scarce research resources will continue to be wasted. One possible explanation for the witnessed nonpublication that warrants further investigation is the issue of publication bias or selective reporting bias, two known problems that decrease research productivity and ethics.

Non-publication and publication bias in reproductive medicine: a cohort analysis.

STUDY QUESTION: Does publication bias or non-publication exist in fertility trials presented as conference abstracts? SUMMARY ANSWER: This study did not detect any publication bias; however, it did identify a high level of non-publication, with only 49% of abstracts reaching full-text publication four or more years after abstract presentation. WHAT IS KNOWN ALREADY: Systematic reviews of randomized controlled trials (RCTs) are the foundation of evidence based medicine. Non-publication or publication deficit refer to the failure to publish trial results. A publication bias exists when there is any tendency on the parts of the investigators or editors to fail to publish study results on the basis or strength of the study findings. Both present a serious problem for researchers, clinicians and policymakers alike, and ultimately impact on patient care. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study identified 337 fertility RCTs presented as conference abstracts between 2007 and 2010, as captured by an electronic search of the Cochrane Gynaecology and Fertility Database. After excluding ineligible trials and duplicates, 224 abstracts remained. PARTICIPANTS/MATERIALS, SETTING, METHODS: A search for the full-text papers of each abstract was undertaken in Pubmed, MEDLINE, Embase, CINAHL and Google in May 2015 using a probabilistic approach. Trial authors were contacted to query the publication status of abstracts when no full-text was identified. The association between individual variables and the probability of publication, and time to publication, was assessed using logistic regression and Cox regression, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 224 included abstracts, only 110 (49%; 95% CI: 42.6, 55.6) were found to be published as full-text articles. Publication bias was not identified in this cohort; studies with positive results had a similar probability of reaching full-text publication 52/113 (46%; 95% CI: 37.0, 55.3) as studies with non-positive (negative or null) results 58/111 (52%; 95% CI: 17.8, 33.9) (adjusted odds ratio (AOR): 1.02; 95% CI: 0.53, 1.97). Similarly, the time from abstract presentation to full-text publication was similar in studies with positive and non-positive results. Oral presentations were more likely to be published, and to be published sooner, than poster presentations (poster presentation AOR: 0.31; 95% CI: 0.15, 0.61 and adjusted hazard ratio (AHR): 0.57; 95% CI: 0.38, 0.86). Studies that were not registered were less likely to be published and to have delayed publication, than studies which were registered either prospectively or retrospectively (AOR: 0.14; 95% CI: 0.04, 0.44 and AHR: 0.43; 95% CI: 0.25, 0.72). Abstracts which were presented a longer time ago also had a higher probability of reaching full-text publication (P  = 0.01). LIMITATIONS, REASONS FOR CAUTION: Commencing with a cohort of RCTs from ethics committee registers may provide a better picture of the extent of non-publication and publication bias, as not all trials reach the stage of abstract presentation. It is also possible that the search did not identify all published trials, as some may have been published after the follow-up period. WIDER IMPLICATIONS OF THE FINDINGS: This study did not identify any publication bias. However, only half of the abstracts in this cohort have been published as full-text articles, four or more years after their presentation at a conference. This is similar to publication rates reported previously for fertility trials, and is despite increasing awareness of the importance of publishing trial results, and subsequent requirements for all RCTs to be registered prior to trial initiation. A better understanding of the reasons for non-publication should assist in facilitating the prompt full-text publication of RCTs in the future. STUDY FUNDING/COMPETING INTEREST(S): Funding provided from the University of Auckland. All authors declare they have no conflicts of interest in relation to this article. TRIAL REGISTRATION NUMBER: Not applicable.

Discontinuation and nonpublication of nasopharyngeal carcinoma clinical trials.

OBJECTIVES: To determine the extent of research waste in the field of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: In this cross-sectional study, we explored the rates, causes and predictors of discontinuation and nonpublication of NPC clinical trials. The sample was derived using the ClinicalTrials.gov advanced search function. Adjusted logistic regression was used to ascertain the effect of trial characteristics on completion and publication status. If a trial discontinuation explanation or publication status could not be determined through the systematic search, the corresponding author was emailed. RESULTS: Ultimately, 311 NPC clinical trials were included (255 [82.0 %] completed and 56 [18.0 %] discontinued trials). The most common reason for trial discontinuation was poor accrual (50 %, 23/46). Industry funding (adjusted OR, 3.12; P = 0.003) and recurrent/metastatic setting (adjusted OR, 11.95; P = 0.003) were significantly associated with increased likelihood of trial discontinuation. Of the 207 completed trials included in the publication query, 141 (68.1 %) were published in peer-reviewed journals, 10 (4.8 %) had results only available on ClinicalTrials.gov, and 56 (27.1 %) remained unpublished 3 or more years after trial completion. Radiation with or without pharmacologic interventions significantly increased the potential of publication (adjusted OR, 3.20; P = 0.048). Among published trials, the median time to publication was 28.47 months (interquartile range, 15.27-44.98 months). CONCLUSION: We identified the difficulties inherent in NPC clinical trials from completion to publication. This represents considerable research waste in NPC, thus raising ethical concerns about the concealment of clinical data and futile patient participation and attendant risks.

Discontinuation and nonpublication of clinical trials in orthopaedic oncology.

BACKGROUND: Despite the pivotal role of clinical trials in advancing orthopaedic oncology knowledge and treatment strategies, the persistent issues of trial discontinuation and nonpublication are significant problems. This study conducted an analysis examining clinical trial discontinuation rates, associations between intervention types and discontinuation/nonpublication, and the role of funding, enrollment size, and their implications for trial success and completion. METHODS: This study, conducted on May 1, 2023, utilized a cross-sectional design to comprehensively analyze phase 3 and 4 randomized controlled trials within the realm of orthopaedic oncology. We specifically incorporated Phase 3 and 4 trials as they are designed to evaluate prolonged outcomes in human subjects and are more likely to reach publication. Study characteristics of interest included the intervention utilized in the clinical trial, presence of funding, whether the trial was published, completed, and trial enrollment size. The investigation involved an examination of ClinicalTrials.gov, a prominent online repository of clinical trial data managed by the National Library of Medicine of the USA. Descriptive statistics and multivariate logistic regressions were used to determine statistical significance. RESULTS: Among the cohort of 130 trials, 19.2% were prematurely discontinued. Completion rates varied based on intervention type; 111 pharmaceutical trials demonstrated a completion rate of 83.8%, whereas 19 non-pharmaceutical trials exhibited a completion rate of 8.0% (P < .001). Surgical trials, totaling 10, showed a completion rate of 90%. The overall trial publication rate was 86.15%, with pharmaceutical interventions achieving a publication rate of 91.96%. Larger-scale trials (≥ 261 participants) emerged as a protective factor against both discontinuation (Adjusted Odds Ratio [AOR]: 0.85, 95% Confidence Interval [CI] 0.42-0.95) and nonpublication (AOR: 0.19, 95% CI 0.13-.47), compared to smaller-scale trials. CONCLUSION: This study accentuates the heightened vulnerability of non-pharmaceutical interventions and trials exhibiting lower rates of enrollment to the issues of discontinuation and nonpublication. Moving forward, the advancement of clinical trials necessitates a concerted effort to enhance trial methodologies, especially concerning nonpharmaceutical interventions, along with a meticulous refinement of participant enrollment criteria.

Discontinuation and nonpublication analysis of chronic pain randomized controlled trials.

Introduction: The primary objective of this cross-sectional analysis is to evaluate rates of discontinuation and nonpublication of Randomized controlled trials (RCTs) of therapeutic interventions to treat chronic pain. Methods: Using ClinicalTrials.gov, a sample was obtained which included clinical trials pertaining to chronic pain. Trials were analyzed for publication status and completion status of each trial. If information was unavailable on the trial registry database, or could not be allocated through a systematic search, the corresponding trialist was contacted and data points were gathered. Results: In our final analysis of the 408 RCTs, we found that 281 (68.9%) were published in a peer-reviewed journal and 127 (31.1%) were unpublished trials. Of 112 discontinued trials, 59 (52.7%) reached publication. In addition, 221 of 296 completed trials (74.7%) were published, and 75 (25.3%) remained unpublished after trial completion. The most common listed reason for trial discontinuation was administrative recommendations (41 of 71 trials [57.7%]), while not receiving an email reply to our standardized email from the corresponding trialist was the most common result for trial nonpublication (49 of 88 trials [55.7%]). Clinical trials funded by nonindustry sponsors were more likely to reach publication than industry-funded clinical trials (unadjusted odds ratio 1.86 [95% CI, 1.18-2.95]; adjusted odds ratio 3.01 [95% CI, 1.76-5.14]). Conclusion: The rate of discontinuation of RCTs involving patients with chronic pain is concerning. Chronic pain affects many patients; thus, the importance of having quality data from clinical trials cannot be overstated. Our study indicates that chronic pain RCTs are frequently discontinued and their findings often go unpublished - all of which could provide crucial information to providers and patients regarding the treatment of chronic pain. We offer suggestions to enhance chronic pain RCT completion, thereby reducing the waste of resources in chronic pain research.

Rates of discontinuation and non-publication of upper and lower extremity fracture clinical trials.

PURPOSE: To our knowledge, no study has quantified the rate of discontinuation and nonpublication of randomized controlled trials (RCTs) regarding upper and lower extremity fractures. METHODS: We searched ClinicalTrials.gov on September 9th, 2020, for phase 3 and 4 RCTs pertaining to upper and lower extremity fractures. Trial completion status was determined using records available on ClinicalTrials.gov. Publication status was determined using records on ClinicalTrials.gov and by searching PubMed (MEDLINE), Embase, and Google Scholar. We queried corresponding authors on trial status if a peer-reviewed publication was not identified. RESULTS: Our final analysis included 142 RCTs, of which 57 (40.1%) were discontinued and 71 (50%) were unpublished. Thirty-six (of 57, 63.2%) discontinued trials failed to provide a reason for discontinuation, the most commonly identified reason for discontinuation was due to inadequate recruitment (13/21, 61.9%). Completed trials were more likely to reach publication (59/85; 69.4%; X2 = 32.92; P ≤ 0.001) than discontinued trials. Trials with more than 80 participants were less likely not to reach publication (AOR: 0.12; 95% CI 0.15-0.66). CONCLUSION: Our analysis of 142 upper and lower extremity fracture RCTs demonstrated one-half failed to reach publication and two-fifths were discontinued prior to trial completion. These findings indicate the need for increased guidance in developing, completing, and publishing RCTs in upper and lower extremity fractures. Discontinuation and nonpublication of orthopaedic RCTs hinder the public's access to collected data and negate the valued contribution from study participants. Discontinuation and non-publication of clinical trials may subject participants to potentially harmful interventions, limit the advancement of clinical research, and contribute to research waste. LEVEL OF EVIDENCE: III.

Industry Sponsor Influence in Clinical Trial Reporting in Canada: A Qualitative Interview Study.

PURPOSE: Approximately 40% of randomized controlled trials are not published, leading to publication bias and less informed clinical decision-making. Qualitative interviews were conducted to understand whether and how industry sponsors of clinical trials of drugs and biologics in Canada influence decisions to report trial results. METHODS: Participants eligible for an interview included clinical trial investigators and research coordinators with experience in drug research, research ethics board members with at least 1 year of experience in ethical review of trials, research administrators with knowledge of dissemination of clinical trial findings or relations with trial sponsors, and trial participants who had taken part in a drug trial as an adult in the 5 years before their interview. Semi-structured interviews were held in person or by telephone between March 2019 and April 2021 with participants in Alberta, British Columbia, and Ontario, Canada. Qualitative analysis included coding of interview transcripts and identification of key themes. FINDINGS: Interviews were conducted with 34 participants, including 17 clinical trial investigators, 1 clinical research coordinator, 3 research administrators, 3 research ethics board members, and 10 clinical trial participants. Participants involved in the conduct, administration, or ethical review of trials represented a range of medical disciplines. Interview participant accounts indicated that in some cases, industry sponsors influence whether results are reported. A core theme was that companies have a weaker incentive to publish trials with unfavorable findings and trials for products that they have decided not to develop further. Companies may influence reporting in various ways, including stopping trials early and not reporting results of stopped trials, owning and controlling access to data, and negotiating clinical trial agreements in multicenter trials that do not fully protect the ability of investigators to publish. Internal company trials represent an additional source of unpublished trials. More broadly, the research system creates a dependency on funding from industry sponsors that may weaken the ability of researchers and research institutions to negotiate terms with industry sponsors that would fully protect publication rights. IMPLICATIONS: Interviews with trial investigators and others connected to trial research indicate that in some cases, industry sponsors of clinical trial research in Canada influence whether results are reported. Policies aiming to bring about full reporting of trials could benefit from considering the commercial incentives of companies and the ways in which industry sponsors may influence clinical trial reporting. Future research could examine the generalizability of these findings to other jurisdictions.

Is there resource wastage in the research for spinal diseases? An observational analysis of discontinuation and non-publication in randomised controlled trials.

Introduction: The scale of waste in research funding systems is large and detrimental to research capacity. Both incompleteness and non-publication of Randomised Controlled Trials (RCTs) have been increasingly reported in the literature. This is a serious consequence as RCTs demand monumental amounts of healthcare resources leading to wastage. Most importantly, both under-reporting and non-publication can distort the evidence landscape and obscure rationale behind clinical decisions. Research question: We, therefore, aimed at conducting the first systematic assessment of registered trial discontinuation and non-publication in the field of spinal disorders. Material and methods: A list of RCTs was obtained from the U.S National Library of Medicine ClinicalTrials.gov database from January 1st, 2013, to December 31st, 2020. Two independent authors excluded all non-RCTs, trials unrelated to spinal diseases, and trials that are in or before the recruitment phase. We extracted the progress status, sources of funding, the number of centres, type of intervention, principal investigator's department affiliation, publication status, location, the reason for discontinuation, publication date, and subtopics. Results: 112 trials were included in the study. 25 (22%) trials were discontinued early, with slow recruitment being the major reason (38%). Only 56 (50%) of the trials were published in peer-reviewed journals. The publication rate amongst discontinued trials was significantly lower compared to completed trials (P â€‹< â€‹0·001). The trial discontinuation rate was much higher in trials registered in the United States (US) compared to other countries (P â€‹= â€‹0·009). Industry-sponsored studies had 11 trials (23·4%) that were discontinued whilst there was 20% of non-industry-sponsored studies that were unfinished. Only 20% of the trials were compliant with the FDA reporting requirements over the study period. Discussion and conclusion: Nearly a quarter of all trials in spinal disorders were discontinued. Half of the trials were unpublished. There was over a third of trials that were completed but not published. These rates remain worrisome from an ethical and financial perspective. Both under-reporting and non-publication adversely affect efforts in evidence synthesis and can compromise clinical guideline development.

Individual and Institutional Factors Preventing Completion of Research by Medical Graduate Students at Cairo University: Questionnaire Study.

BACKGROUND: Medical research plays a significant role in advancing the level of health care worldwide. This research is a crucial part of the development of any educational system. In developing countries, the publication rate related to the medical sciences is lower than that in developed countries. OBJECTIVE: The aim of this study was to explore the causes of delay in publishing research and the factors that hinder the completion of master's degree projects in a group of medical graduate students at Cairo University Faculty of Medicine. METHODS: A web-based questionnaire was introduced to approximately 150 medical graduates in different specialties through social media. The questionnaire aimed to investigate the reasons for delays in publishing master's degree manuscripts after graduation among a group of medical graduates. RESULTS: Of the graduates contacted, 130 responded to the web-based survey. The ages of the participants ranged from 23-38 years (SD 3.88); 72 of them were male, and 58 were female. Causes of noncompletion of manuscripts were analyzed; lack of proper research training and the absence of supportive mentorship were top reasons. We found a significant relationship between being married and failing to complete the assigned project from its start up to publication. Moreover, we found that the frequency of nonfulfillment increased among those who experienced poor mentorship. CONCLUSIONS: Several factors are contributing to the delay in publication of medical manuscripts related to research projects by medical graduates of the Cairo University Faculty of Medicine. Pensive supervision must be implemented to decipher the persistent institutional problems that obstruct research progress.

Discontinuation and non-publication of heart failure randomized controlled trials: a call to publish all trial results.

AIMS: Discontinuation or non-publication of trials may hinder scientific progress and violates the commitment made to research participants. We sought to identify the prevalence of discontinuation and non-publication of heart failure (HF) clinical trials. METHODS AND RESULTS: We conducted a cross-sectional search of ClinicalTrials.gov to identify all completed and discontinued HF clinical trials. We limited our search to only include trials that were completed by 31 December 2017. Trials were investigated to identify reasons for discontinuation. Informative termination was defined as trial termination due to safety or efficacy concerns. Data pertaining to the trial phase, funding, intervention, enrolment, and trial completion date were extracted for each trial. A total of 572 trials were included. Of these, 21% (n = 118) were discontinued before completion. Patient accrual was the most frequently cited reason (n = 42; 36%) for trial discontinuation, followed by informative termination (n = 16; 14%) and funding (n = 14; 12%). Overall, 24 780 patients were enrolled in trials that were terminated. Of trials that were completed and not terminated, nearly one-third (n = 131/454; 29%) were not published. Seventy-nine (24%) trials were published within 12 months, 192 (59%) within 24 months, and 252 (78%) trials within 36 months. CONCLUSIONS: Discontinuation and non-publication of HF trials is common. This raises ethical concerns towards participants who volunteer for research and are exposed to potential risks, inconvenience, and discomfort without furthering scientific progress.

Discontinuation and nonpublication of interventional clinical trials conducted in patients with mild cognitive impairment and Alzheimer's disease.

INTRODUCTION: Discontinuation and nonpublication of interventional clinical trials represents a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in patients afflicted by mild cognitive impairment and Alzheimer's disease. METHODS: We conducted a retrospective, cross-sectional study on mild cognitive impairment and Alzheimer's disease-based interventional clinical trials in ClinicalTrials.gov dating back to 1995. The analyzed data included trial phase, intervention type, enrollment, and funding sources. Fisher's exact and χ2 tests were used to determine any potential associations between trial characteristics and completion. RESULTS: A total of 744 studies were identified, of which 502 (67%) were industry-sponsored ones. A total of 127 (17%) were discontinued prematurely. Of the 617 completed trials, 450 (73%) were not published, representing approximately 66,655 participants who incurred the risks of trial participation without subsequently contributing to the medical literature. Similarly, there were 18,246 patients from unpublished, discontinued trials. Of the 744 trials examined, 247 publications from 167 trials could be identified via PubMed/MEDLINE and EMBASE searches. Most notably, the odds of nonpublication among industry-sponsored trials were more than 75% higher than those in studies funded by academia (odds ratio = 1.78; 95% confidence interval, 1.14-2.78; P = .01). Furthermore, industry-sponsored trials had a 50% greater odds of study discontinuation compared with trials funded by academia (odds ratio = 1.50; 95% confidence interval, 1.04-2.16; P = .03). DISCUSSION: The nonpublication of many trials and preliminary results of trials that are discontinued early dilutes the quality and decreases the comprehensive nature of the medical literature. This occurs in both industry and academia. Publication of inconclusive or negative results ensures that all research activities, regardless of outcome, contribute to global medical knowledge.

Discontinuation and non-publication of clinical trials in cardiovascular medicine.

BACKGROUND: Appropriate dissemination of clinical data is crucial for minimising bias. Despite this, high rates of study discontinuation and non-publication have been reported among clinical trials. Cardiovascular medicine receives a substantial proportion of academic funding; however, predictors of non-publication among cardiovascular trials are not well-established. METHODS: The National Clinical Trials database was searched for cardiovascular trials completed between January 2010 and January 2014. Associated publications were identified in Medline or Embase. Relevant variables were extracted and subject to chi-squared and logistic regression to identify predictors of discontinuation and non-publication. RESULTS: After reviewing 2035 trials, 431 trials were included, of which 82.1% (n=354; 119,233 participants) were completed. Among completed trials, 70.3% (n=249; 99,095 participants) were published. Industry funding was associated with increased likelihood of non-publication (odds ratio [OR] 2.84; 95% confidence interval [CI] 1.47-5.51; P=0.002), while non-randomised studies were more likely to remain unpublished than randomised counterparts. Industry-funded studies were over three times more likely to be discontinued than those sponsored by academic institutions (OR 3.89; CI 1.54-9.83; P=0.004). Trials studying heart failure and atrial fibrillation were more likely to be discontinued compared to trials studying coronary artery disease (OR 2.83; CI 1.23-6.51; and OR 3.10; CI 1.21-7.96, respectively). Of the total 135,714 participants, 25,565 were recruited into unpublished studies. CONCLUSIONS: Discontinuation and non-publication of cardiovascular trials are common, resulting in data from thousands of participants remaining unpublished. Funding source and randomisation are strong predictors of non-publication, while sponsor type, phase and blinding status are key predictors of discontinuation.

Discontinuation and non-publication of randomised clinical trials supported by the main public funding body in Switzerland: a retrospective cohort study.

OBJECTIVE: The Swiss National Science Foundation (SNSF) promotes academic excellence through competitive selection of study proposals and rigorous evaluation of feasibility, but completion status and publication history of SNSF-supported randomised clinical trials (RCTs) remain unclear. The main objectives were to review all healthcare RCTs supported by the SNSF for trial discontinuation and non-publication, to investigate potential risk factors for trial discontinuation due to poor recruitment and non-publication, and to compare findings to other Swiss RCTs not supported by the SNSF. DESIGN: We established a retrospective cohort of all SNSF-supported RCTs for which recruitment and funding had ended in 2015 or earlier. For each RCT, two investigators independently searched corresponding publications in electronic databases. In addition, we approached all principal investigators to ask for additional publications and information about trial discontinuation. Teams of two investigators independently extracted details about study design, recruitment of participants, outcomes, analysis and sample size from the original proposal and, if available, from trial registries and publications. We used multivariable regression analysis to explore potential risk factors associated with discontinuation due to poor recruitment and with non-publication, and to compare our results with data from a previous cohort of Swiss RCTs not supported by the SNSF. RESULTS: We included 101 RCTs supported by the SNSF between 1986 and 2015. Eighty-seven (86%) principal investigators responded to our survey. Overall, 69 (68%) RCTs were completed, 26 (26%) RCTs were prematurely discontinued (all due to slow recruitment) and the completion status remained unclear for 6 (6%) RCTs. For analysing publication status, we excluded 4 RCTs for which follow-up was still ongoing and 9 for which manuscripts were still in preparation. Of the remaining 88 RCTs, 53 (60%) were published as full articles in peer-reviewed journals. Multivariable regression models suggested that discontinued trials were at higher risk for non-publication than completed trials (adjusted OR 7.61; 95% CI 2.44 to 27.09). Compared with other Swiss RCTs, the risk of discontinuation for SNSF-supported RCTs was higher than in industry-initiated RCTs (adjusted OR 3.84; 95% CI 1.68 to 8.74), but not significantly different from investigator-initiated RCTs not supported by the SNSF (adjusted OR 1.05; 95% CI 0.51 to 2.11). We found no evidence that the proportion of discontinued or unpublished RCTs decreased over the last 20 years. CONCLUSIONS: One out of four SNSF-supported RCTs were prematurely discontinued due to slow recruitment, 40% of all included RCTs and 70% of all discontinued RCTs were not published in peer-reviewed journals. There is a case to reconsider how public funding bodies such as the SNSF could improve their feasibility assessment and promote publication of RCTs irrespective of completion status.

Network meta-analyses performed by contracting companies and commissioned by industry.

BACKGROUND: Industry commissions contracting companies to perform network meta-analysis for health technology assessment (HTA) and reimbursement submissions. Our objective was to estimate the number of network meta-analyses performed by consulting companies contracted by industry, to assess whether they were published, and to explore reasons for non-publication. METHODS: We searched MEDLINE for network meta-analyses of randomized trials. Papers were included if they had authors affiliated with any contracting company. All identified contracting companies as well as additional ones from the list of the exhibitors at the International Society for Pharmacoeconomics and Outcomes Research, an annual meeting that representatives from many contracting companies attend and exhibit at, were surveyed regarding conduct and publication of network meta-analyses. RESULTS: In 162 of 822 (20%) network meta-analysis papers, authors were affiliated to 66 contracting companies. Another 36 contracting companies were identified by the exhibitors list. Three companies had no contact information and six merged with others, therefore 93 companies were contacted. Thirty seven out of ninety three (40%) companies responded, and 19 indicated that they had performed a total of 476 network meta-analyses, but only 102 (21%) papers were published. Thirteen companies that disclosed to have conducted 174 network meta-analyses (45 published) provided reasons for non-publication. Of the 129 still unpublished meta-analyses, for 40 there were plans for future publication, for 37 the sponsor did not allow publication, for 16 the contracting companies did not plan to publish the meta-analysis, for another 23 plans were unclear, and the remaining 13 were used as HTA submission. The protocol of the network meta-analysis was publically available from 11/162 (6.8%) network meta-analyses published by authors affiliated with contracting companies. CONCLUSIONS: There is a prolific sector of professional contracting companies that perform network meta-analyses. Industry commissions many network meta-analyses, but most are not registered before or published after analyses in the scientific literature. Mechanisms to improve publication rates of network meta-analysis commissioned by industry are warranted.