• 21st century cures: is US medicines bill a colossal mistake?

      Doshi, Peter (BMJ Publishing Group, 2015-07-23)
    • Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology

      Bourgeois, Florence; Hong, Kyungwan; Lee, Haeyoung; Shamseer, Larissa; Spence, O'Mareen; Jefferson, Tom; Doshi, Peter; Jones, Mark A., B.Sc., Ph.D. (BMJ, 2020-03-17)
      Purpose: Trustworthy reporting of quadrivalent human papillomavirus (HPV) vaccine trials is the foundation for assessing the vaccine’s risks and benefits. However, several pivotal trial publications incompletely reported important methodological details and inaccurately described the formulation that the control arms received. Under the Restoring Invisible and Abandoned Trials initiative (RIAT), we aim to restore the public record regarding the content and rationale of the controls used in the trials. Methods: We assembled a cohort (five randomised controlled trials) described as placebo-controlled using clinical study reports (CSRs) obtained from the European Medicines Agency. We extracted the content and rationale for the choice of control used in each trial across six data sources: trial publications, register records, CSR synopses, CSR main bodies, protocols and informed consent forms. Results: Across data sources, the controlwas inconsistently reported as ‘placebo’- containing aluminium adjuvant (sometimes with dose information). Amorphous aluminium hydroxyphosphate sulfate (AAHS) was not mentioned in any trial registry entry, but was mentioned in all publications and CSRs. In three of five trials, consent forms described the control as an ‘inactive’ substance. No rationale for the selection of the control was reported in any trial publication, register, consent form, CSR synopsis or protocol. Three trials reported the rationale for choice of control in CSRs: to preserve blinding and assess the safety of HPV virus-like particles as the ‘safety profile of (AAHS) is well characterised’. Conclusions: The stated rationale of using AAHS control—to characterise the safety of the HPV virus-like particles—lacks clinical relevance. A nonplacebo control may have obscured an accurate assessment of safety and the participant consent process of some trials raises ethical concerns. Trial registration numbers NCT00092482, NCT00092521, NCT00092534, NCT00090220, NCT00090285.
    • Another question for GSK

      Doshi, Peter; Jefferson, Tom (BMJ Publishing Group, 2010-06-29)
    • Antibiotics Approved for Marketing in Populations Specifically Excluded From Premarketing Trials, 1999-2018

      Kuzucan, Aida; Powers, John H; Doshi, Peter
      Approval by the US Food and Drug Administration (FDA) of a drug for a given indication is thought to reassure clinicians, other health care providers, and patients that substantial evidence of effectiveness exists for specific indicated populations (patients and diseases). This study examines whether FDA approval of certain antibiotics should be so reassuring for all patient populations identified in the FDA-approved labels. Specifically, this study compared patient populations covered by FDA-approved labels for 21 novel antibiotics approved between 1999 and 2018 to the patient exclusion and inclusion criteria of pivotal trials that supported those approvals. We found that every FDA-approved label for these antibiotics included at least one identifiable patient population that was explicitly excluded from enrolling in the supporting pivotal trials. Two antibiotics, bedaquiline and ceftazidime-avibactam, were approved for use in populations that were fully excluded from enrolling in registration trials.
    • Are manufacturers sharing data as promised?

      Doshi, Peter; Mayo-Wilson, Evan; Dickersin, Kay (BMJ Publishing Group, 2015-09-25)
    • Are US flu death figures more PR than science?

      Doshi, Peter (BMJ Publishing Group, 2005-12-10)
    • Assessing Muscle-Related Adverse Events in Randomized Trials of Statins.

      Doshi, Peter; Hong, Kyungwan; Tanveer, Sarah; Jefferson, Tom (Springer Nature, 2022-03-16)
    • Authors' reply to Dunning

      Doshi, Peter; Jefferson, Tom (BMJ Publishing Group, 2014-04-30)
    • Calibrated response to emerging infections

      Doshi, Peter (BMJ Publishing Group, 2009-09-03)
    • Cherry-picking by trialists and meta-analysts can drive conclusions about intervention efficacy

      Doshi, Peter (Elsevier, 2017-08-22)
      Objective: To determine whether disagreements among multiple data sources affect systematic reviews of randomized clinical trials (RCTs). Study Design and Setting: Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and non-public sources (clinical study reports [CSRs] and individual participant data [IPD]). Results: We found 21 gabapentin RCTs (74 reports, six IPD) and seven quetiapine RCTs (50 reports, one IPD); most were reported in journal articles (18/21 [86%] and 6/7 [86%], respectively). When available, CSRs contained the most trial design and risk of bias information. CSRs and IPD contained the most results. For the outcome domains “pain intensity” (gabapentin) and “depression” (quetiapine), we found single trials with 68 and 98 different meta-analyzable results, respectively; by purposefully selecting one meta-analyzable result for each RCT, we could change the overall result for pain intensity from effective (standardized mean difference [SMD]=-0.45; 95%CI -0.63 to -0.27) to ineffective (SMD=-0.06; 95%CI -0.24 to 0.12). We could change the effect for depression from a medium effect (SMD=-0.55; 95%CI -0.85 to -0.25) to a small effect (SMD=-0.26; 95%CI -0.41 to -0.1). Conclusions: Disagreements across data sources affect the effect size, statistical significance, and interpretation of trials and meta-analyses.
    • Clinical trial data: get them while you can

      Doshi, Peter; Groves, Trish; Loder, Elizabeth (BMJ Publishing Group, 2014-01-06)
    • Contradictory findings on efficacy of neuraminidase inhibitors not cited

      Doshi, Peter; Jefferson, Tom; Heneghan, Carl; Jones, Mark A., B.Sc., Ph.D. (Oxford University Press (OUP), 2020-04-24)
    • Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies

      Spelsberg, Angela; Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich (BMJ Publishing Group, 2017-02-07)
      Objectives: To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act. Design: Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10. Setting: Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany. Main outcome measures: Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions. Results: Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals. Conclusions: Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor. High remuneration and strict confidentiality clauses in these studies could influence the physicians’ reporting behaviours of adverse drug reactions.
    • Convicting Zika

      Doshi, Peter (BMJ Publishing Group, 2016-04-07)
    • Covid-19 vaccine trial protocols released

      Doshi, Peter (BMJ Publishing Group, 2020-10-21)
    • Covid-19 vaccines and treatments: we must have raw data, now

      Doshi, Peter; Godlee, Fiona; Abbasi, Kamran (BMJ, 2022-01-19)