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Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial
Asger Sand Paludan-Müller1, Michelle C Ogden1, Mikkel Marquardsen1
1Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark.
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.
Insights
Few new clinical trials adequately consider previous evidence, potentially exposing participants to suboptimal treatments. Ethical approval processes should mandate systematic literature searches to ensure robust trial justification and reduce research waste.
Area of Science:
- Clinical trial methodology
- Research ethics
- Evidence-based medicine
Background:
- New clinical trials are essential for advancing medical knowledge.
- Ensuring new trials build upon existing evidence is crucial for efficiency and participant safety.
- The extent to which prior research informs new trial design is not well-documented.
Purpose of the Study:
- To assess the consideration of previous trial evidence in new randomized trial protocols.
- To evaluate the justification and evidence base for newly proposed clinical trials.
Main Methods:
- A cohort study of randomized trial protocols approved by Danish ethics committees (January 2012 - March 2013).
- Protocols were screened for explicit mention of literature searches and evidence of systematic searches.
- Simple search strategies were used to identify potentially relevant cited or uncited trials.
Main Results:
- Only 3% of 67 protocols explicitly stated conducting a literature search; only 1% allowed replication.
- 16% of protocols had insufficient information to judge ethical justification due to comparator or rationale issues.
- Relevant prior trials that could have supported justification were identified for 12% of protocols.
Conclusions:
- A substantial minority of new trials may lack a sufficient evidence base.
- The limited use of literature searches hinders the assessment of prior evidence consideration.
- Mandatory systematic literature searches for ethical approval are recommended to prevent research waste and protect participants.
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