Wednesday, August 26, 2020

Rapid, Up-to-Date Evidence Synthesis in the Time of COVID

In emergent situations with sparse and rapidly evolving bodies of research, evidence synthesis programs must be able to adapt to a shortened timeline to provide clinicians with the best available evidence for decision-making. (See our previous posts on rapid systematic review and guideline development, here, here, here, and here). But perhaps no health crisis in the modern era has made this more clear than the coronavirus disease 2019 (COVID-19) pandemic.

Recently, Murad and colleagues published a framework detailing a four-pillar program through which they have been able to synthesize evidence related to the COVID-19 pandemic. This system has been tried and tested within the Mayo Clinic, a multi-state academic center with more than 1.2 million patients per year.


Launched within two weeks of the World Health Organization’s declaration of COVID-19 as a pandemic, Mayo Clinic’s evidence synthesis program consisted of four major components:

  • What is New?: an automatically generated list of COVID-19-related studies published within the last three days and categorized into topic areas such as diagnosis or prevention
  • Repository of Studies: a running list of previously published studies since the first case report of COVID-19, including those that move from the “What is New?” list after three days’ time
  • Rapid Reviews: reviews published within three to four days in response to pressing clinical questions from those on the frontlines and utilizing the study repository. To facilitate evidence synthesis, studies are often screened and selected by a single reviewer and evidence is rarely meta-analyzed.
  • Repository of Reviews: a collection of reviews including those developed at Mayo and elsewhere, identified in twice-weekly searches and through a list of predetermined websites. To supplement knowledge, some reviews included indirect evidence borrowed from studies of other coronaviruses or respiratory infections, when appropriate.
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Within one month of the framework’s establishment, the team had conducted seven in-house rapid reviews and had indexed more than 100 newly published reviews into a database housing over 2,000 total.

The authors conclude that while an intensive system such as this may not be feasible in smaller health systems, cross-collaboration and sharing of knowledge can allow for informed and up-to-date clinical care that adapts in the face of a rapidly changing landscape of evidence.

Murad, M.H., Nayfeh, T., Suarez, M.U., Seisa, M.O., Abd-Rabu, R., Farah, M.H.E..., & Saadi, S.M. 2020. A framework for evidence synthesis programs to respond to a pandemic. Mayo Clin Proc 95(7):1426-1429.

Manuscript available at the publisher's website here.

Friday, August 14, 2020

New Elaboration of CONSORT Items Aims to Improve the Reporting of Deprescribing Trials

Deprescribing is the act of withdrawing a treatment prescription from patients for whom a medication has become inappropriate or in whom the risks may now outweigh the benefits. However, trials examining the effects of deprescribing are often complex and multi-faceted, and reporting of these trials can miss important aspects such as patient selection and length of follow-up. 

A recently published paper by Blom et al. used a multistep process to develop a reporting guideline for deprescribing trials based on a systematic review of this body of research, paying close attention to those aspects that most commonly went unreported. The result was an elaboration of the Consolidated Standards of Reporting Trials (CONSORT) statement, with the addition of items reviewed by a panel of 14 experts in the areas of ranging from pharmacology and geriatric medicine to statistics and reporting guidelines. The process, which ended with a one-day face-to-face meeting to approve the elaborated items, also took into account the Template for Intervention Description and Replication (TIDieR) checklist to ensure that a comprehensive list was created.

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The panel determined that all items of the original CONSORT checklist are applicable to deprescribing trials, but that certain items required further detail. The CONSORT items that required the most attention with regards to deprescribing studies included the following:

  • description of trial design
  • participant selection 
  • detailed information that would allow replication of the intervention studied
  • pre-specification of primary and secondary outcome
  • discussion of adverse events and harms, including those related to drug withdrawal
  • defined periods of recruitment and follow-up


In addition to improving the quality of reporting in deprescribing trials, the authors also recommend increasing the amount of dedicated funds available for deprescribing studies, which are currently scarce and not incentivized by common streams of research funding.

Blom, J.W., Muth, C., Glasziou, P., McCormarck, J.P., Perera, R., Poortvliet, R.K.E..., & Knottnerus, J.A. 2020. Describing deprescribing trials better: An elaboration of the CONSORT statement. J Clin Epidemiol 127: 87-95.

Manuscript available from the publisher's website here.

Thursday, August 6, 2020

New Systematic Review Suggests Noncordance with COI Disclosure to Reporting Databases is Widespread, but Methodological Quality of Studies is Variable

Disclosure of conflict of interest (COI) is a major point of concern in the development of guidelines as well as original research papers. Over the years, multiple studies have aimed to elucidate just how closely the disclosures of individual authors tracks with their reported COI in open databases. A new systematic review of 27 such studies, recently published online in the Journal of Clinical Epidemiology, compiles the findings of these studies into some eyebrow-raising statistics while also taking a look at the methodological quality of these studies.


In their review, El-Rayass and colleagues found that although the methodological quality for assessing the concordance of authors’ COI disclosures within papers and according to public databases varied widely, a median of 81.2% of authors across 20 studies had “noncorcordant” disclosures, (ranging from 41.8% to 98.6% across all studies) and that more than half (43.4% of all authors) of these were “completely nonconcordant” (ranging from 15% to 89.5% across all studies). What’s more, among seven studies that analyzed company reporting on the individual level, between 23.1% and 85.4% of companies did not report their payments to authors.

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For the five studies that analyzed disclosures on the study rather than the individual author level, all found at least some degree of discordance between in-study disclosures and database reports. The rate of nonconcordant disclosures among these studies ranged from 6 to 92.6%


The authors note that ulterior motives of authors are just one potential explanation for the high observed rate of nonconcordant COI disclosure and reporting. Vague instructions and parameters set by journals during the article submission process may undermine efforts to transparently report any and all potential sources of conflict, be they financial, intellectual or otherwise. In addition, the authors found that studies of COI reporting that tended to have higher methodological quality also tended to report lower estimates of nonconcordance, meaning that the overall combined estimates may be artificially inflated – for instance, due to some studies not making a distinction about the relevancy of potential COI sources to the topic of the articles analyzed. The authors note potential sources of nondirectional error as well, such as how differences in COI categories between in-paper disclosures and reference databases were handled, which additionally lowers confidence in the current estimate.

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In sum, the recent review by El-Rayess et al. points out that issues with concordance between authors’ COI disclosures in their published works seem to be at odds with publicly available reports of these relationships; however, the degree of nonconcordance overall is still uncertain. Those looking to complete future analyses of COI disclosure policies may want to use this paper as a roadmap to improving our certainty in the actual magnitude of the issue.

El-Rayess, H., Khamis, A.M., Haddad, S., Ghaddara, H.A., Hakoum, M., Ichkhanian, Y., Bejjani, M., and Akl, E.A. Assessing concordance of financial conflicts of interest disclosures with payments' databases: A systematic survey of the health literature. J Clin Epidemiol 127:19-28.

Manuscript available at the publisher's website here.