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• “Because when you finalize the trial, the meta-analysis will be outdated.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” |