That is the subtitle of a paper by Vreman et al. (2020). The authors look at all treatments approved by FDA and EMA that were subsequently reviewed by HTA bodies in both jurisdictions between 1995 and 2018. The authors used ICER as the US HTA body; European HTA bodies included IQWiG (Germany), NICE (UK), ZIN (Netherlands), and EUnetHTA. From these reports the authors classified any uncertainties mentioned into six categories:
- Safety: small sample size, causality of adverse events uninterpretable, long-term safety
- Trial validity: Selection bias, performance bias, detection bias, attrition bias, reporting bias
- Population: Population does not match practice, subgroups not adequately studied/reported
- Intervention: Unreliable or missing information on interactions with other medication, unreliable or missing information on monotherapy or combination regimen, unreliable or missing information on appropriate treatment duration
- Comparative effects: Unreliable or missing information on effects against relevant comparators, unreliable indirect comparisons, unreliable or missing information on appropriate treatment line
- Outcomes: Unreliable or missing information on long-term effects, relevant outcomes not measured or reported
Using this approach, the authors evaluated 33 drugs, covering 34 indications. The authors found that 7.4 uncertainties (SD 3.8) were raised per drug per institution, with HTA bodies more likely to raise uncertainties compared to regulators. What did the authors find:
Safety issues—such as those related to sample size or uncertainties in causality—were raised by regulators for almost all drugs assessed (94% for the FDA and 85% for the EMA). HTA bodies raised safety issues for only 59% (ICER) and 53% (AGGR-EUR) of drugs…
HTA bodies raised uncertainties related to effects against relevant comparators for almost all drugs (100% in the United States and 88% in Europe), whereas this category was hardly addressed by the FDA (12%) and only slightly more by the EMA (32%).
One can see the breakdown by category visually in the graph below.
Interesting throughout. You can read the full paper here.