Missing clinical trial data: the evidence gap in primary data for potential COVID-19 drugs
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Abstract
Background
Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of overall clinical trial results on public registries or through academic publication. We aimed to analyse the evidence gap in this data by conducting a rapid review of results posting on ClinicalTrials.gov and in academic publications to quantify the number of trials missing results for drugs potentially being repurposed for COVID-19.
Methods
ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for results and for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance.
Results
Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. Tabular results were available on ClinicalTrials.gov for 1172 (31.2%) completed trials. A further 1066 (28.4%) had published results in the academic literature, but did not report results on ClinicalTrials.gov . Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%).
Conclusions
There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause unnecessary additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.
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SciScore for 10.1101/2020.05.30.20117523: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding The protocol during the second review remained unchanged and researchers were blinded to the results of the first review. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:However, the proportion of studies with results available in the academic literature is an approximation and there are …
SciScore for 10.1101/2020.05.30.20117523: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding The protocol during the second review remained unchanged and researchers were blinded to the results of the first review. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:However, the proportion of studies with results available in the academic literature is an approximation and there are several limitations to our study. Firstly, our trial population was limited only to those registered on ClinicalTrials.gov. While ClinicalTrials.gov is the largest registry in the world, with over 340,000 registrations as of writing and an order of magnitude greater than the next largest journal, additional trials on these therapies may have been registered elsewhere. However, it is unlikely that these would be expected to report at a different rate than those registered to ClinicalTrials.gov. Secondly, our strategy for locating publications included only those listed on ClinicalTrials.gov and identified through searches on PubMed and Google Scholar, which are open-access resources that should cover a majority of published clinical research. While including proprietary databases like Scopus or Ovid may have located some additional publications, we do not believe this would have substantially impacted our overall results (34). Thirdly, we are aware that trials that were not registered at all or published in non-English language journals without inclusion of the NCT number would not have been captured by our methodology. Finally, searcher heterogeneity and difficulty identifying results publication in the academic literature limits accuracy in any manual publication search, however, our search strategy was standardised and produced a high level of agreement bet...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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