Peter Doshi’s research while affiliated with University of Maryland, Baltimore and other places

"Spin" refers to misleading reporting, interpretation, and extrapolation of findings in primary and secondary research (such as in systematic reviews). The study of spin primarily focuses on beneficial outcomes. The objectives of this research were threefold: first, to develop a framework for identifying spin associated with harms in systematic reviews of interventions; second, to apply the framework to a set of reviews, thereby pinpointing instances where spin may be present; and finally, to revise the spin examples, offering guidance on how spin can be rectified. The authors developed their framework through an iterative process that engaged an international group of researchers specializing in spin and reporting bias. The framework comprises 12 specific types of spin for harms, grouped by 7 categories across the 3 domains (reporting, interpretation, and extrapolation). The authors subsequently gathered instances of spin from a random sample of 100 systematic reviews of interventions. Of the 58 reviews that assessed harm and the 42 that did not, they found that 28 (48%) and 6 (14%), respectively, had at least 1 of the 12 types of spin for harms. Inappropriate extrapolation of the results and conclusions for harms to populations, interventions, outcomes, or settings not assessed in a review was the most common category of spin in 17 of 100 reviews. The authors revised the examples to remove spin, taking into consideration the context (for example, medical discipline, source population), findings for harms, and methodological limitations of the original reviews. They provide guidance for authors, peer reviewers, and editors in recognizing and rectifying or (preferably) avoiding spin, ultimately enhancing the clarity and accuracy of harms reporting in systematic review publications.

Background/aims: Inadequate description of trial interventions in publications has been repeatedly reported, a problem that extends to the description of placebo controls. Without describing placebo contents, it cannot be assumed that a placebo is inert. Pharmacologically active placebos complicate accurate estimation and interpretation of efficacy and safety data. In this study, we sought to assess whether placebo contents are described in study protocols and publications of trials published in high-impact medical journals. Methods: We identified all placebo-controlled randomized clinical trials (RCTs) published in 2016 in Annals of Internal Medicine, The BMJ, the Journal of the American Medical Association (JAMA), The Lancet, and the New England Journal of Medicine (NEJM). We included all trials with publicly available study protocols. From journal publications and associated study protocols, we searched and recorded: description of placebo contents; the amount of each placebo ingredient; and investigators' stated rationale for selection of placebo ingredients. Results: We included 113 placebo-controlled RCTs. Of the 113 trials, placebo content was described in 22 (19.5%) journal publications and 51 (45.1%) study protocols. The amount of each placebo ingredient was described in 15 (13.3%) journal publications and 47 (41.6%) study protocols. None of the journal publications explained the rationale for the choice of placebo ingredients, whereas a rationale was provided in 4 (3.5%) study protocols. The stated rationales were to ensure the placebo was visually indistinguishable from the experimental intervention (N = 3) and ensure comparability with a previous study (N = 1). Conclusion: There is no accessible record of the composition of placebos for approximately half of high-impact RCTs, even with access to study protocols. This impedes reproducibility and raises unanswerable questions about what effects-beneficial or harmful-the placebo may have had on trial participants, potentially confounding an accurate assessment of the experimental intervention's safety and efficacy. Considering that study protocols are unabridged, detailed documents describing the trial design and methodology, the fact that less than half of the study protocols described the placebo contents raises concerns about clinical trial transparency. To improve the reproducibility and potential of placebo-controlled RCTs to provide reliable evidence on the efficacy and safety profile of drugs and other experimental interventions, more detail regarding placebo contents must be included in trial documents.

Introduction In 2020, prior to COVID-19 vaccine rollout, the Brighton Collaboration created a priority list, endorsed by the World Health Organization, of potential adverse events relevant to COVID-19 vaccines. We adapted the Brighton Collaboration list to evaluate serious adverse events of special interest observed in mRNA COVID-19 vaccine trials. Methods Secondary analysis of serious adverse events reported in the placebo-controlled, phase III randomized clinical trials of Pfizer and Moderna mRNA COVID-19 vaccines in adults (NCT04368728 and NCT04470427), focusing analysis on Brighton Collaboration adverse events of special interest. Results Pfizer and Moderna mRNA COVID-19 vaccines were associated with an excess risk of serious adverse events of special interest of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2 (95 % CI −0.4 to 20.6 and −3.6 to 33.8), respectively. Combined, the mRNA vaccines were associated with an excess risk of serious adverse events of special interest of 12.5 per 10,000 vaccinated (95 % CI 2.1 to 22.9); risk ratio 1.43 (95 % CI 1.07 to 1.92). The Pfizer trial exhibited a 36 % higher risk of serious adverse events in the vaccine group; risk difference 18.0 per 10,000 vaccinated (95 % CI 1.2 to 34.9); risk ratio 1.36 (95 % CI 1.02 to 1.83). The Moderna trial exhibited a 6 % higher risk of serious adverse events in the vaccine group: risk difference 7.1 per 10,000 (95 % CI –23.2 to 37.4); risk ratio 1.06 (95 % CI 0.84 to 1.33). Combined, there was a 16 % higher risk of serious adverse events in mRNA vaccine recipients: risk difference 13.2 (95 % CI −3.2 to 29.6); risk ratio 1.16 (95 % CI 0.97 to 1.39). Discussion The excess risk of serious adverse events found in our study points to the need for formal harm-benefit analyses, particularly those that are stratified according to risk of serious COVID-19 outcomes. These analyses will require public release of participant level datasets.