Doctor of Philosophy, Universite Claude-Bernard (Lyon I) (2017)
John Ioannidis, Postdoctoral Faculty Sponsor
Do patients with cystic fibrosis participating in clinical trials demonstrate placebo response? A meta-analysis.
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
BACKGROUND: Patients' and families' expectation that a cure for cystic fibrosis (CF) will be found is high. In other debilitating conditions, high expectation has been shown to drive a strong placebo response (PR). Therefore, our goal was to evaluate PR on objective continuous outcomes (FEV1, BMI) and the CF Questionnaire Revised-Respiratory Domain (CFQR-RD) monitored during randomised clinical trials (RCTs) for CF.METHODS: We conducted a meta-analysis after a systematic review of the literature carried out to identify RCTs with FEV1, CFQR-RD and BMI as outcome measures. The standardised mean difference (SMD) was calculated to estimate the PR. A meta-regression analysis was conducted to assess other contributing factors on PR such as study design, trial duration, patient age and disease severity.RESULTS: Out of 289 RCTs found in the search, we identified 61 articles (published from 1987 to 2017) with respectively 59, 17 and 9 reporting FEV1, CFQR-RD and BMI at the start and at the end of the RCTs. No significant PR was found on FEV1 or CFQR-RD. However, a small but significant PR was found on BMI SMD, 0.09 (95% CI (0.01; 0.17); p = 0.03).CONCLUSION: The PR seems higher when measuring BMI. However, it is not clear whether this improvement can be explained by a PR alone.
View details for DOI 10.1016/j.jcf.2019.02.003
View details for PubMedID 30772244
New clinical trial designs in the era of precision medicine: An overview of definitions, strengths, weaknesses, and current use in oncology.
Cancer treatment reviews
2018; 73: 20–30
With expanding knowledge in tumor biology and biomarkers, oncology therapies are increasingly moving away from the "one-size-fits-all" rationale onto biomarker-driven therapies tailored according to patient-specific characteristics, most commonly the tumor's molecular profile. The advent of precision medicine in oncology has been accompanied by the introduction of novel clinical trial designs that aim to identify biomarker-matched subgroups of patients that will benefit the most from targeted therapies. This innovation comes with the promise of answering more treatment questions, more efficiently and in less time. In this article, we give an overview of the different biomarker-based designs, comparing the features of enrichment, randomize-all, umbrella, and basket trials, and highlighting their advantages and disadvantages. We focus more on the novel designs known as master protocols, which include umbrella and basket trials. We have also conducted a search in ClinicalTrials.gov for registered oncology-related protocols of ongoing or completed trials labeled as umbrella or basket trials for solid tumors; we also included additional relevant trials retrieved from other reviews. We present and discuss the key features of the 30 eligible basket trials and 27 eligible umbrella trials. Only a minority of them are randomized (2 and 9, respectively), including three trials with adaptive randomization. Five of these trials have been completed as of July 2018. Precision medicine trial designs fuel new hopes for identifying best treatments, but there is also the potential for hype. The benefits and challenges associated with their use will need continued monitoring.
View details for DOI 10.1016/j.ctrv.2018.12.003
View details for PubMedID 30572165
- Correction to: Industry-funded versus non-profit-funded critical care research: a meta-epidemiological overview. Intensive care medicine 2018
Industry-funded versus non-profit-funded critical care research: a meta-epidemiological overview.
Intensive care medicine
PURPOSE: To study the landscape of funding in intensive care research and assess whether the reported outcomes of industry-funded randomized controlled trials (RCTs) are more favorable.METHODS: We systematically assembled meta-analyses evaluating any type of intervention in the critical care setting and reporting the source of funding for each included RCT. Furthermore, when the intervention was a drug or biologic, we searched also the original RCT articles, when their funding information was unavailable in the meta-analysis. We then qualitatively summarized the sources of funding. For binary outcomes, separate summary odds ratios were calculated for trials with and without industry funding. We then calculated the ratio of odds ratios (RORs) and the summary ROR (sROR) across topics. ROR<1 implies that the experimental intervention is relatively more favorable in trials with industry funding compared with trials without industry funding. For RCTs included in the ROR analysis, we also examined the conclusions of their abstract.RESULTS: Across 67 topics with 568 RCTs, 88 were funded by industry and another 73 had both industry and non-profit funding. Across 33 topics with binary outcomes, the sROR was 1.10 [95% CI (0.96-1.26), I2=1%]. Conclusions were not significantly more commonly unfavorable for the experimental arm interventions in industry-funded trials (21.3%) compared with trials without industry funding (18.2%).CONCLUSION: Industry-funded RCTs are the minority in intensive care. We found no evidence that industry-funded trials in intensive care yield more favorable results or are less likely to reach unfavorable conclusions.
View details for DOI 10.1007/s00134-018-5325-3
View details for PubMedID 30151688
- Assessment of Pragmatism in Recently Published Randomized Clinical Trials. JAMA internal medicine 2018