ArticleTherapeutic innovation & regulatory science2026
Predicting the Treatment Regimen Estimand in Phase 3 Studies from the Estimated Efficacy Estimand Based on Phase 2 Data.
Article in Therapeutic innovation & regulatory science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe ICH E9 (R1) addendum establishes frameworks for efficacy estimands (using a hypothetical strategy to handle intercurrent events) and treatment regimen estimands (using a treatment policy strategy to handle intercurrent events) in clinical trials. While Phase 3 studies often adopt treatment regimen estimands for regulatory purposes, direct use of the results from Phase 2 treatment regimen estimands for Phase 3 planning may produce suboptimal results due to differences in population, study duration, treatment regimen itself, and treatment delivery methods that affect adherence rates.
methodsWe developed a modeling framework that decomposes treatment regimen estimands into adherent (efficacy estimand) and non-adherent patient responses. Using historical Phase 3 study data from chronic weight management and type 2 diabetes populations, we first establish empirical linear relationships between efficacy and non-adherent responses through regression modeling without intercept. Then we estimate Phase 3 efficacy responses from Phase 2 data, project discontinuation rates for Phase 3 study, and apply the empirical relationship to predict treatment regimen responses.
resultsLinear relationships were identified for change in absolute weight loss and glycated hemoglobin (HbA1c) endpoints using data from multiple Phase 3 studies. Model validation showed close agreement between predicted and observed treatment regimen responses in the training data. Application to the SURPASS-2 Phase 3 study demonstrated reasonable predictive accuracy, with estimates generally within expected ranges of observed results.
conclusionsThis approach provides a systematic method for translating Phase 2 efficacy estimand results into Phase 3 treatment regimen estimand predictions. It leverages empirical relationships between efficacy responses and non-adherent responses, and may complement direct Phase 2 data extrapolation, particularly for endpoints where treatment effects persist after discontinuation. Current applications focus on change in body weight (kg) and change in HbA1c (%).
Indexed as
Identifiers
42315826What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.