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Table 2 Key free text quotes from responses

From: Synthesizing existing evidence to design future trials: survey of methodologists from European institutions

From respondents who answered “No” or “Possibly” to the question “Would you be willing to consider a conditional trial design next time you plan a trial?”

 • “Lots of examples where a large definitive trial has contradicted the results of a meta-analysis of smaller trials”

 • “Any meta-analysis is observational research”

 • “Because when you finalize the trial, the meta-analysis will be outdated. Your study should be a standalone trial”

 • “Not enough faith in the homogeneity/comparability of the studies”

 • “The assumptions behind a meta-analysis (homogeneity, no publication bias), are very rarely plausible, so a typical RCT has to offer a chance of providing a definitive conclusion on its own”

 • “Clinical trials are perceived as independent pieces of evidence. There would need to be a major shift by regulators, HTA bodies and physicians for companies to design trials in the context of meta-analyses”

 • “Usually the context in which I work is of trials supporting applications for a license. Regulators require each study to be ‘significant’ independently of others”

 • “Wonder whether it would be convincing to authorities”

 • “In the regulatory context, meta-analyses are typically NOT considered for approval decisions, at least not directly. (Typically). I would answer differently for publicly funded studies. A newish suggestion—most of our trials are phase II/III, where things are a little different”

From respondents who replied “Other” to the question “What do you think is the biggest barrier towards adopting conditional trial design in designing trials?”

 • “Although trials can be planned to add just enough power to an existing meta-analysis, there is a high risk that such planning fails because of wrong assumptions, differences in study execution, or other reasons”

 • “It is flawed and too risky (why give an experimental drug in an underpowered study)”

 • “Guidelines from important regulatory and health economic agencies”

 • “Lack of dissemination”

 • “Skepticism as trials should be powered to stand alone, I would think. All other studies in the MA may not be comparable or of high quality”

 • “It’s not necessarily logical”

 • “I don’t believe this is an appropriate way to design trials”

  1. HTA health technology assessment, MA meta-analysis, RCT randomized controlled trial