Time to subsequent therapy (TTST) as an endpoint in clinical studies: development of standardized documentation of subsequent therapy through systematic literature review, expert interviews, and Delphi survey.

Bianca Biedenweg; Thorsten Ruppert; Thomas Kohlmann; Martin Danner; Anja Mehnert-Theuerkauf; Diana L&#xfc;ftner; Ulrike Filippig; Janine Ziemann; Ulrike Osowski; Peter Kaskel

doi:10.1007/s00432-026-06583-w

PubMed · 42742636

Time to subsequent therapy (TTST) as an endpoint in clinical studies: development of standardized documentation of subsequent therapy through systematic literature review, expert interviews, and Delphi survey.

Bianca Biedenweg·Thorsten Ruppert·Thomas Kohlmann·Martin Danner·Anja Mehnert-Theuerkauf·Diana Lüftner·Ulrike Filippig·Janine Ziemann·Ulrike Osowski·Peter Kaskel

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Abstract

BACKGROUND: The endpoint Time to Subsequent Therapy (TTST) is an intermediate endpoint used in research and regulatory assessments. TTST denotes initiation of subsequent therapy and is a clearly definable, clinically relevant event for healthcare professionals. However, it has not been systematically established to which extent TTST is subjectively meaningful to patients. The objective of this study was to define TTST as a patient-relevant intermediate endpoint. METHODS: The study examined five oncological indications (breast cancer, prostate cancer, melanoma, multiple myeloma, and non-small cell lung cancer) using a systematic literature review, analysis of case report forms used in international randomized controlled trials, review of German Federal Joint Committee (G-BA) documents, semi-structured interviews and a two-stage Delphi survey with healthcare professionals, patients, and relatives. RESULTS: A total of 35 individuals participated in qualitative interviews. Most of them rated TTST as particularly significant. The Delphi Survey included 264 interviewees in round one, and 117 in round two. Patient-relevance of TTST was confirmed by 81% of respondents (95% confidence interval 76%, 85%). Nine treatment scenarios that justify TTST were identified. To capture patient-relevance, prospective collection of reasons for and consequences of therapy change are required. A checklist with standardized response formats plus free-text fields was developed: a comprehensive master checklist for flexible, complete documentation and a short version focused on therapy change-specific items. CONCLUSIONS: TTST is an intermediate endpoint whose systematic documentation of characteristics demonstrating patient-relevance can be standardized in research and clinical practice using the developed checklists.

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Humans Delphi Technique Neoplasms Male Female Documentation Endpoint Determination Time-to-Treatment Benefit assessment Endpoint Oncology Patient relevance TTST Time to subsequent therapy Journal Article Systematic Review

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Bianca Biedenweg, Thorsten Ruppert, Thomas Kohlmann, Martin Danner, Anja Mehnert-Theuerkauf, Diana Lüftner, Ulrike Filippig, Janine Ziemann, Ulrike Osowski, Peter Kaskel. 2026-09-02. Time to subsequent therapy (TTST) as an endpoint in clinical studies: development of standardized documentation of subsequent therapy through systematic literature review, expert interviews, and Delphi survey.. https://doi.org/10.1007/s00432-026-06583-w

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Journal Article; Systematic Review resource Delphi Technique subject Female subject Humans subject Journal Article subject Male subject Neoplasms subject Oncology subject Systematic reviews study

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