Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

Autor: Nicolas Methy, Franck Bonnetain, Laurent Bedenne
Přispěvatelé: BMC, Ed., Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL )
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Oncology
Cancer Research
Time Factors
Digestive System Neoplasms
[ SDV.CAN ] Life Sciences [q-bio]/Cancer
0302 clinical medicine
Quality of life
Surveys and Questionnaires
Medicine
030212 general & internal medicine
MESH: Treatment Outcome
Response rate (survey)
MESH : Evidence-Based Medicine
Clinical Trials as Topic
Evidence-Based Medicine
MESH: Endpoint Determination
MESH: Research Design
MESH : Questionnaires
MESH : Research Design
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
MESH: Reproducibility of Results
medicine.anatomical_structure
Treatment Outcome
Research Design
030220 oncology & carcinogenesis
Data Interpretation
Statistical
MESH: Survival Analysis
MESH : Disease-Free Survival
MESH : Endpoint Determination
France
MESH : Time Factors
Research Article
medicine.medical_specialty
MESH: Clinical Trials as Topic
Endpoint Determination
Rectum
[SDV.CAN]Life Sciences [q-bio]/Cancer
MESH : Treatment Outcome
lcsh:RC254-282
Disease-Free Survival
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
Internal medicine
Genetics
Humans
MESH : Data Interpretation
Statistical
MESH : France
Survival analysis
MESH: Humans
business.industry
Surrogate endpoint
MESH: Digestive System Neoplasms
MESH : Reproducibility of Results
MESH: Questionnaires
MESH : Humans
MESH: Time Factors
Cancer
Reproducibility of Results
MESH: Quality of Life
MESH : Quality of Life
medicine.disease
Survival Analysis
MESH : Clinical Trials as Topic
MESH: France
Localized disease
MESH: Disease-Free Survival
Quality of Life
MESH : Digestive System Neoplasms
MESH : Survival Analysis
business
MESH: Data Interpretation
Statistical
MESH: Evidence-Based Medicine
Zdroj: BMC Cancer, Vol 10, Iss 1, p 277 (2010)
BMC Cancer
BMC Cancer, BioMed Central, 2010, 10 (1), pp.277. ⟨10.1186/1471-2407-10-277⟩
BMC Cancer, BioMed Central, 2010, 10 (1), pp.277. 〈10.1186/1471-2407-10-277〉
ISSN: 1471-2407
DOI: 10.1186/1471-2407-10-277⟩
Popis: Background Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). Methods In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion. Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Results Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS. DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations. Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed. Conclusion The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.
Databáze: OpenAIRE
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