Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols

Objective To investigate to what extent evidence from previous similar trials or systematic reviews was considered before conducting new trials.Design Cohort study of contemporary protocols for trials with ethical approval.Methods All protocols for randomised trials approved by the five ethical comm...

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Main Authors: Asger Sand Paludan-Müller, Peter Christian Gøtzsche, Michelle C Ogden, Mikkel Marquardsen, Jonas Vive, Karsten Juhl Jørgensen
Format: Article
Language:English
Published: BMJ Publishing Group 2019-11-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/11/e026661.full
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author Asger Sand Paludan-Müller
Peter Christian Gøtzsche
Michelle C Ogden
Mikkel Marquardsen
Jonas Vive
Karsten Juhl Jørgensen
author_facet Asger Sand Paludan-Müller
Peter Christian Gøtzsche
Michelle C Ogden
Mikkel Marquardsen
Jonas Vive
Karsten Juhl Jørgensen
author_sort Asger Sand Paludan-Müller
collection DOAJ
description Objective To investigate to what extent evidence from previous similar trials or systematic reviews was considered before conducting new trials.Design Cohort study of contemporary protocols for trials with ethical approval.Methods All protocols for randomised trials approved by the five ethical committees in Denmark between January 2012 and March 2013 were screened for eligibility. Included protocols were read in full to determine whether a systematic search had been conducted and references were checked to evaluate whether trial rationale and design could be challenged for not adequately considering previous evidence. To investigate whether protocols cited relevant trials, we used simple search strategies that could easily be conducted by researchers without experience with literature searches.Results Sixty-seven protocols were included. Only two (3%) of the protocols explicitly stated to have conducted a literature search and only one (1%) provided information that allowed the search to be replicated. Eleven (16%) of the protocols described trials where we found the information insufficient to judge if the trial was ethically justified, either due to a comparator that was not supported by the presented evidence (six protocols), because they did not present a rationale for conducting the trial (two protocols), or for both reasons (three protocols). For eight (12%) of the protocols, our search identified trials that could have been relevant to cite as justification.Conclusions While most protocols seem to adequately consider existing evidence, a substantial minority of trials might lack a sufficient evidence base. Very few trials seemed to have been based on a literature search which makes it impossible to know whether all relevant previous trials had been considered. Rules for ethical approval should include requirements for systematic literature searches to ensure that research participants are not exposed to sub-optimal treatments or unnecessary harms as well as to reduce research waste.
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spelling doaj-art-2f3644994cd64b8280f4ae43a1e32b342024-11-30T00:35:11ZengBMJ Publishing GroupBMJ Open2044-60552019-11-0191110.1136/bmjopen-2018-026661Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocolsAsger Sand Paludan-Müller0Peter Christian Gøtzsche1Michelle C Ogden2Mikkel Marquardsen3Jonas Vive4Karsten Juhl Jørgensen51 Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark1 Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark1 Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark1 Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark1 Nordic Cochrane Centre, Rigshospitalet, Copenhagen, DenmarkCentre for Evidence-Based Medicine Odense (CEBMO) and Cochrane Denmark, University of Southern Denmark, Odense, DenmarkObjective To investigate to what extent evidence from previous similar trials or systematic reviews was considered before conducting new trials.Design Cohort study of contemporary protocols for trials with ethical approval.Methods All protocols for randomised trials approved by the five ethical committees in Denmark between January 2012 and March 2013 were screened for eligibility. Included protocols were read in full to determine whether a systematic search had been conducted and references were checked to evaluate whether trial rationale and design could be challenged for not adequately considering previous evidence. To investigate whether protocols cited relevant trials, we used simple search strategies that could easily be conducted by researchers without experience with literature searches.Results Sixty-seven protocols were included. Only two (3%) of the protocols explicitly stated to have conducted a literature search and only one (1%) provided information that allowed the search to be replicated. Eleven (16%) of the protocols described trials where we found the information insufficient to judge if the trial was ethically justified, either due to a comparator that was not supported by the presented evidence (six protocols), because they did not present a rationale for conducting the trial (two protocols), or for both reasons (three protocols). For eight (12%) of the protocols, our search identified trials that could have been relevant to cite as justification.Conclusions While most protocols seem to adequately consider existing evidence, a substantial minority of trials might lack a sufficient evidence base. Very few trials seemed to have been based on a literature search which makes it impossible to know whether all relevant previous trials had been considered. Rules for ethical approval should include requirements for systematic literature searches to ensure that research participants are not exposed to sub-optimal treatments or unnecessary harms as well as to reduce research waste.https://bmjopen.bmj.com/content/9/11/e026661.full
spellingShingle Asger Sand Paludan-Müller
Peter Christian Gøtzsche
Michelle C Ogden
Mikkel Marquardsen
Jonas Vive
Karsten Juhl Jørgensen
Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols
BMJ Open
title Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols
title_full Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols
title_fullStr Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols
title_full_unstemmed Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols
title_short Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols
title_sort do protocols for new randomised trials take previous similar trials into account cohort study of contemporary trial protocols
url https://bmjopen.bmj.com/content/9/11/e026661.full
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