Platform trials

Rethinking the pros and cons of randomized controlled trials and observational studies in the era of big data and advanced methods: a panel discussion

“…This leads to predetermined changes based on the analyses of accumulating data, all the while maintaining trial validity and integrity [ 15 ] Despite being more complex than traditional RCTs, adaptive trials can bring about numerous benefits, such as shortening trial duration or obtaining more precise conclusions [ 15 ] Jardine et al 2022 [ 25 ] Wang et al 2018 [ 26 ] Sequential trials Sequential trials are an approach to clinical trials during which subjects are serially recruited and study results are continuously analyzed [ 16 ]. Once enough data enabling a decision regarding treatment effectiveness is collected, the trial is stopped [ 17 ] Since a sequential trial can be halted as soon as treatment efficacy or lack thereof is demonstrated, a reliable result is obtained with a minimum number of patients [ 16 ] Lewis and Bessen 1990 [ 16 ] Gu et al 2015 [ 27 ] Platform trials Platform trials are a type of clinical trial during which multiple interventions can be compared simultaneously to a common control group within a single master protocol [ 28 ] With a platform trial, having a common control arm can decrease the number of patients to be enrolled, the cost, and the time of a RCT [ 29 ] Parker et al 2018 [ 30 ] Yee et al 2022 [ 31 ] EHR (Electronic Health Record)-based clinical trials EHRs and an expanded access to routinely-collected clinical data has resulted in RCTs being conducted within the context of EHR-based clinical trials. [ 19 ] EHRs may facilitate pre-screening of patients by age, sex, and diagnosis, helping to exclude ineligible patients, and reduce the overall screening duration in clinical trials [ 32 ] Price et al 2017 [ 33 ] Bereznicki et al 2008 [ 34 ] Observational studies Innovation Definition Strengths Application of the method Causal infer...…”

How Much More Efficient Are Adaptive Platform Trials Than Multiple Stand‐Alone Trials? A Comprehensive Simulation Study for Streamlining Drug Development During a Pandemic

“…However, in APT‐nonSPE, where patient enrollment for each drug was initiated at different times, the non‐concurrent randomized control group that included patients who did not undergo randomization concurrently emerged during the trials. The use of data on such nonconcurrent randomized controls, in addition to concurrent controls, can improve the efficiency of increasing the power for statistical hypothesis testing but could bias the study results due to time trends 23–26 . In the COVID‐19 setting, because of the change in the virus variants over time, the initiation of vaccination and spread of infection resulting in immunity during the trials can affect the 28‐day mortality rate, we used only concurrent randomized controls in the statistical comparison of the 28‐day mortality rate between the drug and placebo groups in the simulation studies.…”

“…The use of data on such nonconcurrent randomized controls, in addition to concurrent controls, can improve the efficiency of increasing the power for statistical hypothesis testing but could bias the study results due to time trends. [23][24][25][26] In the COVID-19 setting, because of the change in the virus variants over time, the initiation of vaccination and spread of infection resulting in immunity during the trials can affect the 28-day mortality rate, we used only concurrent randomized controls in the statistical comparison of the 28-day mortality rate between the drug and placebo groups in the simulation studies. Although some statistical approaches for adjusting the time-trend bias…”