When to stop immune checkpoint inhibitor for malignant melanoma? Challenges in emulating target trials
Observational data have become a popular source of evidence for causal effects when no randomized controlled trial exists, or to supplement information provided by those. In practice, a wide range of designs and analytical choices exist, and one recent approach relies on the target trial emulation framework. This framework is particularly well suited to mimic what could be obtained in a specific randomized controlled trial, while avoiding time-related selection biases. In this abstract, we present how this framework could be useful to emulate trials in malignant melanoma, and the challenges faced when planning such a study using longitudinal observational data from a cohort study. More specifically, two questions are envisaged: duration of immune checkpoint inhibitors, and trials comparing treatment strategies for BRAF V600-mutant patients (targeted therapy as 1st line, followed by immunotherapy as 2nd line, vs. immunotherapy as 2nd line followed by targeted therapy as 1st line). Using data from 1027 participants to the MELBASE cohort, we detail the results for the emulation of a trial where immune checkpoint inhibitor would be stopped at 6 months vs. continued, in patients in response or with stable disease.
Impact evaluation for COVID-19 non-pharmaceutical interventions: what is (un)knowable?
COVID-19 non-pharmaceutical intervention (NPI) policies have been one of the most important and contentious decisions of our time. Beyond even the "normal" inherent difficulties in impact evaluation with observational data, COVID-19 NPI policy evaluation is complicated by additional challenges related to infectious disease dynamics and lags, lack of direct observation of key outcomes, and a multiplicity of interventions occurring on an accelerated time scale. Randomized controlled trials also suffer from what is feasible and ethical to randomize as well as the sheer scale, scope, time, and resources required for an NPI trial to be informative (or at least not misinformative). In this talk, Dr. Haber will discuss the challenges in generating useful evidence for COVID-19 NPIs, the landscape of the literature, and highlight key controversies in several high profile studies over the course of the pandemic. Chasing after unknowables poses major problems for the metascience/replicability movement, institutional research science, and decision makers. If the only choices for informing an important topic are "weak study design" vs "do nothing," when is "do nothing" the best choice?