Colin Dormuth

Background: Selective publication of clinical trials is common and leads to publication bias, but factors contributing to selective publication are not well understood. It is also unclear whether trialists believe they have a duty to trial participants to report their research.Objective: To understand (i) whether and how industry sponsors of clinical trials influence decisions to report trial results, (ii) factors contributing to nonpublication and publication bias, and (iii) how the experiences and views of trial participants, trial investigators, and others connected to clinical trial research relate to whether researchers have a duty to trial participants to report research findings.Design: Qualitative interview study.Participants: 34 participants including 17 clinical trial investigators, 1 clinical research coordinator, 3 research administrators, 3 research ethics board members, and 10 clinical trial participants. Setting: Semistructured interviews conducted in person or by telephone with participants from Alberta, British Columbia, and Ontario, Canada.Analysis: Data analysis was informed by grounded theory, including coding of interview transcripts, memo-writing, and developing key themes.Results: Industry sponsors may influence whether clinical trials are reported through stopping trials early and not reporting results, ownership and control of data, clinical trial agreements which do not fully protect an investigator’s right to publish, control of internal company trials, and funding dependency. While companies have a commercial incentive to selectively report trials, other incentives within clinical research also appear to favour publication of positive over negative trials. Positive findings are perceived to be easier to publish, to help investigator’s ability to access industry and nonindustry research funding, and to be rewarded by research institutions in hiring, promotion and recognition. Interviews suggested that when participants enter a trial, there is often an implicit understanding between researchers and participants involving a responsibility to report results. Accounts of trial investigators suggested reporting research results is a necessary part of honouring informed consent.Conclusions: While clinical trial reporting is valued in Canada, selective reporting of clinical trials arises for a variety of reasons. Policy to promote full reporting of trials may be strengthened by recognizing factors that contribute to nonpublication and publication bias.

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Background: Smoking is the leading cause of preventable death worldwide. Although smoking cessation (SC) pharmacotherapies have been shown to have a moderate short-term benefit as a quitting aid, substantial cardiovascular and neuropsychiatric safety concerns have been identified in adverse reporting databases, leading to prescription label warnings by Health Canada and the U.S. FDA. However, recent studies indicate these warnings may be without merit.Objectives: This thesis examined the comparative safety and effectiveness of medications commonly used to aid smoking cessation. The thesis focused on real-world safety of varenicline, bupropion, and nicotine replacement therapy (NRT). It also demonstrated a novel method of measuring comparative effectiveness using drug therapy re-initiation as a proxy for treatment failure. Design and Setting: Retrospective cohort studies using linked de-identified claims data from the British Columbia Ministry of Health and U.S. MarketScan® databases. Outcomes: The primary safety outcome was a composite of cardiovascular hospitalizations. Secondary safety outcomes included: all-cause mortality, a composite of neuropsychiatric hospitalizations, and individual components of the primary outcome. Effectiveness was measured using drug therapy re-initiation. Statistical Analysis: Propensity score adjusted log-binomial and Cox proportional hazards regression models.Results: 116,442 B.C. participants and 618,497 U.S. participants were analyzed. In the U.S., compared to NRT, varenicline was associated with a 20% lower 1-year CV risk [adjusted risk ratio (RR) = 0.80, 95% Confidence Interval (CI): (0.75 – 0.85)] and bupropion was associated with a 25% lower 1-year CV risk [RR=0.75, 95% CI: (0.69 – 0.81)]. Varenicline was associated with a 26% lower 1-year risk of neuropsychiatric hospitalization versus NRT [RR=0.74, 95% CI: (0.71 – 0.76)]. In B.C., compared to NRT, varenicline was associated with a 20% one-year relative risk decrease of neuropsychiatric hospitalization [RR: 0.80, CI: (0.71 – 0.89)], and a 19% one-year relative risk decrease of mortality [RR: 0.81, CI: (0.71 – 0.93)]. We found no significant difference in risk between NRT and bupropion for cardiovascular hospitalizations, neuropsychiatric hospitalizations, or mortality.Conclusions: Compared to NRT, varenicline was associated with fewer serious adverse events, and bupropion the same number of serious adverse events. Varenicline and bupropion were associated with fewer subsequent SC drug episodes.

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No abstract available.