Registered trials address questions already answered with high-certainty evidence: A sample of current redundant research

Published:February 05, 2021DOI:


      • Redundant trials exist despite previous findings of the same clinical question.
      • Existing high certainty evidence may not be considered when planning new trials.
      • Redundant trials should be avoided because of their ethical implications.



      To identify clinical trials registered later than 2015, that study the effect of an intervention on a primary outcome whose “Certainty of Evidence” (CoE) has already been rated “high” in a Cochrane SR.

      Study Design and Setting

      We searched the Cochrane Library for all SRs from 2015. We analyzed SRs of interventions and excluded withdrawn reviews or those with no Summary of Findings (SoF) table. We retrieved the GRADE CoE ratings of each SR's primary outcomes in the SoF tables and identified those rated “high.” We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials to identify records of clinical studies that tackled those outcomes and were registered after the date of publication of the respective 2015 SR.


      We selected 602 SRs. Eighty-one contained a “high” CoE rating on at least one primary outcome, totaling 152 primary outcomes rated “high.” We found 39 clinical trials registered for primary outcomes with evidence already rated as “high” in a 2015 Cochrane SR.


      This study shows the existence of clinical trials registered to study primary outcomes whose CoE has already been rated “high” in a Cochrane SR.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Clinical Epidemiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Learn About Clinical Studies - [Internet]. [cited 2020 Apr 24]. Available from:

        • Chan A-W
        • Tetzlaff JM
        • Altman DG
        • Laupacis A
        • Gøtzsche PC
        • Krleža-Jerić K
        • et al.
        SPIRIT 2013 statement: defining standard protocol items for clinical trials.
        Ann Intern Med. 2013; 158: 200-207
        • Guyatt GH
        • Oxman AD
        • Vist GE
        • Kunz R
        • Falck-Ytter Y
        • Alonso-Coello P
        • et al.
        GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
        BMJ. 2008; 336: 924-926
      2. Chapter 14: Completing “Summary of findings” tables and grading the certainty of the evidence [Internet]. [cited 2020 Apr 24]. Available from:

        • Guyatt GH
        • Thorlund K
        • Oxman AD
        • Walter SD
        • Patrick D
        • Furukawa TA
        • et al.
        GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles-continuous outcomes.
        J Clin Epidemiol. 2013; 66: 173-183
        • Guyatt GH
        • Oxman AD
        • Santesso N
        • Helfand M
        • Vist G
        • Kunz R
        • et al.
        GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes.
        J Clin Epidemiol. 2013; 66: 158-172
        • Chalmers I
        • Bracken MB
        • Djulbegovic B
        • Garattini S
        • Grant J
        • Gülmezoglu AM
        • et al.
        How to increase value and reduce waste when research priorities are set.
        Lancet. 2014; 383 ( 156-165
        • Glasziou P
        • Altman DG
        • Bossuyt P
        • Boutron I
        • Clarke M
        • Julious S
        • et al.
        Reducing waste from incomplete or unusable reports of biomedical research.
        Lancet. 2014; 383: 267-276
        • Ioannidis JPA
        • Greenland S
        • Hlatky MA
        • Khoury MJ
        • Macleod MR
        • Moher D
        • et al.
        Increasing value and reducing waste in research design, conduct, and analysis.
        Lancet. 2014; 383: 166-175
        • Lau J
        • Antman EM
        • Jimenez-Silva J
        • Kupelnick B
        • Mosteller F
        • Chalmers TC.
        Cumulative meta-analysis of therapeutic trials for myocardial infarction.
        N Engl J Med. 1992; 327: 248-254
      3. A WM. Ethics and medical research. In: Association WM, editor. Medical Ethics Manual, 2015, p. 98–115.

      4. WMA - The World Medical Association-WMA Declaration of Helsinki – ethical principles for medical research involving human subjects [Internet]. [cited 2020 Apr 24]. Available from:

        • Freedman B.
        Equipoise and the ethics of clinical research.
        N Engl J Med. 1987; 317: 141-145
        • Hey SP
        • London AJ
        • Weijer C
        • Rid A
        • Miller F.
        Is the concept of clinical equipoise still relevant to research?.
        BMJ. 2017; 359: j5787
        • Padhy BM
        • Meher BR.
        Seeding trials: Marketing gimmick or credible scientific research.
        Indian J Anaesth. 2019; 63: 235-238
        • Matheson A.
        Marketing trials, marketing tricks - how to spot them and how to stop them.
        Trials. 2017; 18: 105
        • Paludan-Müller AS
        • Ogden MC
        • Marquardsen M
        • Vive J
        • Jørgensen KJ
        • Gøtzsche PC.
        Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols.
        BMJ Open. 2019; 9 (e026661)
        • Clarke M
        • Hopewell S
        • Chalmers I.
        Clinical trials should begin and end with systematic reviews of relevant evidence: 12 years and waiting.
        Lancet. 2010; 376: 20-21
        • Heneghan C
        • Aronson JK.
        Why reports of clinical trials should include updated meta-analyses.
        BMJ Evid Based Med. 2020; 25: 1-2
        • Mahtani KR.
        All health researchers should begin their training by preparing at least one systematic review.
        J R Soc Med. 2016; 109: 264-268
        • Shuster JJ
        Review: cochrane handbook for systematic reviews for interventions.
        Research Synthesis Methods. 2011; 2 (Version 5.1.0, published 3/2011. Julian P.T. Higgins and Sally Green, Editors)
        • Carrasco-Labra A
        • Brignardello-Petersen R
        • Santesso N
        • Neumann I
        • Mustafa RA
        • Mbuagbaw L
        • et al.
        Improving GRADE evidence tables part 1: a randomized trial shows improved understanding of content in summary of findings tables with a new format.
        J Clin Epidemiol. 2016; 74: 7-18
        • Langendam M
        • Carrasco-Labra A
        • Santesso N
        • Mustafa RA
        • Brignardello-Petersen R
        • Ventresca M
        • et al.
        Improving GRADE evidence tables part 2: a systematic survey of explanatory notes shows more guidance is needed.
        J Clin Epidemiol. 2016; 74: 19-27
        • Santesso N
        • Carrasco-Labra A
        • Langendam M
        • Brignardello-Petersen R
        • Mustafa RA
        • Heus P
        • et al.
        Improving GRADE evidence tables part 3: detailed guidance for explanatory footnotes supports creating and understanding GRADE certainty in the evidence judgments.
        J Clin Epidemiol. 2016; 74: 28-39
        • Gartlehner G
        • Dobrescu A
        • Evans TS
        • Bann C
        • Robinson KA
        • Reston J
        • et al.
        The predictive validity of quality of evidence grades for the stability of effect estimates was low: a meta-epidemiological study.
        J Clin Epidemiol. 2016; 70: 52-60
        • Keats EC
        • Haider BA
        • Tam E
        • Bhutta ZA.
        Multiple-micronutrient supplementation for women during pregnancy.
        Cochrane Database Syst Rev. 2019; 3 (CD004905)
        • Norhayati MN
        • Ho JJ
        • Azman MY.
        Influenza vaccines for preventing acute otitis media in infants and children.
        Cochrane Database Syst Rev. 2017; 10CD010089
        • Webster J
        • Osborne S
        • Rickard CM
        • Marsh N.
        Clinically-indicated replacement versus routine replacement of peripheral venous catheters.
        Cochrane Database Syst Rev. 2019; 1 (CD007798)