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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

In brief

Eight in ten view time to next cancer therapy as a meaningful endpoint

In a Delphi survey of 381 clinicians, patients and relatives, 81% affirmed that time to subsequent therapy (TTST) reflects outcomes important to patients across five tumor types. Researchers identified nine scenarios that justify TTST and created a detailed and short checklist to record reasons and effects of therapy changes, enabling standardized, patient-focused reporting.

Journal
Journal of cancer research and clinical oncology (Q1)
Published
2 September 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Bianca Biedenweg, Thorsten Ruppert, Thomas Kohlmann, Martin Danner, Anja Mehnert-Theuerkauf, Diana Lüftner, et al.
PMID
42742636
DOI
10.1007/s00432-026-06583-w

Why clinicians should know about it

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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.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.