1 / 16

Guidelines for endpoint definitions in cancer trials

Guidelines for endpoint definitions in cancer trials. Bonnetain F DATECAN Project on behalf DATECAN steering committee Statisticians from CRLCC, EORTC, FFCD : Bellara C, Collette L, Dousseau A, Gourgou S, Kramar A, Ouali M, Mathoulin S. Rationale.

lali
Download Presentation

Guidelines for endpoint definitions in cancer trials

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Guidelines for endpoint definitionsin cancer trials Bonnetain F DATECAN Project on behalf DATECAN steering committee Statisticians from CRLCC, EORTC, FFCD : Bellara C, Collette L, Dousseau A, Gourgou S, Kramar A, Ouali M, Mathoulin S

  2. Rationale Review of randomized clinical trials in oncology(Mathoulin et coll. JCO 2008) Medlinedatabases 2004: Cancer / RandomisedClinical Trial : 8 journals: Lancet, JAMA, BMJ, NEJM / BJC, JCO, JNCI, Cancer Review of phase II (11) and phase III (104) randomized clinical trials • 1) Heterogeneity in the selection of ‘survival’ endpoints 2) Non-optimal survival endpoint definition

  3. Rationale

  4. Rationale

  5. Rationale

  6. Summary • Definitions of guidelines in publications: • Without formal consensus (rather expert opinion) • Not often used • Available for only few cancer sites • Heterogeneity in: • The selection of time to event (survival) endpoints • The definitions of these endpoints

  7. Events contributing to DFS in adj Colon Cancer MOSAIC/PETACC8 PETACC-3/ACCORD-02 • Locoregional recurrence EE • Distant metastases EE • Second primary, same cancer E E • Second primary, other cancer IE • (Second primary, colorectal) EE • Death from same cancer EE • Death from other cancer E E • Non-cancer related death E E • Treatment related death E E • Loss to follow-up CC • DFS definitions • MOSAIC/PETACC8 • relapse, death, 2nd colorectal cancer • 2nd cancer other than colorectal (ignored) • PETACC-3/ACCORD-02 • relapse, death, 2nd colon cancer • 2nd cancer other than colon (event / RFS including only 2 nd colon cancer)

  8. Summary • Consequences  Difficulties of interpretation • Comparison between trials • Different conclusions according to different definitions • Example: PETACC 03 • (Van Cutsem E et al. J Clin Oncol 2009)(irinotecan / 5-fluorouracil (5-FU) / folinic acid (FA) versus 5-FU/FA in stage III colon cancer) • DFS (with second primary tumors)  Significant difference • DFS (without second primary tumors)  Non significant difference

  9. Objective To develop guidelines for survival endpoints definitions  standardization: • To define terminology • To define events and censoring process

  10. Methods • Identification of selected cancer sites and relevant endpoints, based on literature review • For each cancer site Develop guidelines with: • Consensus methods based on expert opinion obtained in a systematic manner • European consultation • Consultation of experts with various backgrounds (oncologist, surgeon, radiotherapist, biostatistician, …) • Later contact EMEA etc..

  11. Target cancer sites • First year 2010 - 2011 • Sarcomas • Pancreas cancer • Breast cancer • Following years: • Colo-Rectal cancer • GI cancer (Stomach) ± oesophagus • Kidney & Bladder cancer • Lymphomas • Head & Neck cancer • Lung cancer

  12. Consensus method

  13. Example of questionnaire (GI) • Should the following clinical events be regarded as events in the definition of the endpoint Disease Free survival (DFS)? Please place one tick  on each line. • Table 2 (Setting “no detectable disease” only)

  14. EORTC Group contribution • To provide list of experts: • For participation in the design of the questionnaire (2-3) • Inclusion criteria • Experience in the specialty (>15 years: yes / no) • Principal investigator in clinical trials (>3: yes / no) • Participation in research projects (>3 : yes / no) • Publications in the specialty (>3: Yes / No) • For completion of the questionnaire (15-20) • Inclusion criteria • Experience in the specialty (>10 years: yes / no) (not strict) • Principal investigator in clinical trials (>1: yes / no) • Participation in research projects (>1 : yes / no) • Publications in the specialty (>3: Yes / No)

  15. Schedule • January 2010 – May 2010 • List and agreement of expert for Pilot Group and RC for Pancreatic, Sarcoma and Breast • May – Sept 2010 • Creation of questionnaire forms • Validation and pre-test by pilot group (ongoing for breast) • Database constitution and validation (e-crf) • Since Nov 2010 • First round consensus for Pancreatic and Sarcoma

More Related