Lead Investigator: Derek Dinart, Institut Bergonié
Title of Proposal Research: Optimal estimation of the number of subjects in clinical trials to improve the quality of clinical research and the development of new treatments for cancer patients
Vivli Data Request: 8833
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
The majority of randomized controlled trials assessing the risk of death assume that the study populations receiving a drug are similar, and that the drug acts in the same way on everyone. However, this assumption may not be valid in all circumstances. Although it has been described in the literature since the 1970s, the differences encountered in multicentre trial have recently received renewed interest due to concerns about the reliability of reported trial results. We defined in this context the differences as a set of characteristics shared by patients that may influence their risk of death and response to drug. Patients may be statistically related because of their lifestyle or because they are managed in the same care center.
We have recently proposed a method for calculating the number of patients to include in a clinical trial that accounts for all these differences. We have shown in our work that these dependencies (correlations) between patients are difficult to measure (quantifiable), thus leading to the underestimation of the number of patients needed, and thus to a failure of the trials, defined here by the inability to demonstrate the effectiveness of the new drug, when it is really effective. A strength of our approach, that is also one of its weaknesses, is to provide plausible values for potential differences between centers in the design of the trial.
By analyzing multiple trials, we could get a trend regarding the underlying differences in study drug effect and/or risk of death within trials which clearly influence the number of patients that need to be included. However, no work has been done to quantify this. Providing an indication of the size of these differences would allow more accurate estimation of drug effect, and avoid missing potentially effective drugs for patients.
Requested Studies:
A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients With Metastatic Colorectal Cancer (MCRC) Treated With Irinotecan / 5-FU Combination (FOLFIRI) After Failure of an Oxaliplatin Based Regimen
Data Contributor: Sanofi
Study ID: NCT00561470
Sponsor ID: EFC10262
A Randomized, Multicenter, Open-Label Cross-Over Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Patients With HER2-Positive Early Breast Cancer
Data Contributor: Roche
Study ID: NCT03674112
Sponsor ID: MO40628
A Placebo-Controlled, Double-Blind, Multicenter, Randomized, Phase II Study of Bevacizumab in Previously Untreated Extensive-Stage Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT00403403
Sponsor ID: AVF3995g
A Randomized, Open-label Study of the Effect of Herceptin Plus Arimidex Compared With Arimidex Alone on Progression-free Survival in Patients With HER2-positive and Hormone-receptor Positive Metastatic Breast Cancer
Data Contributor: Roche
Study ID: NCT00022672
Sponsor ID: BO16216
Randomized, Open-Label, Phase 3 Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non-Small Cell Lung Cancer
Data Contributor: Lilly
Study ID: NCT00762034
Sponsor ID: 9707
A Multicenter, Randomized, Open-label, 3-Arm Phase 3 Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer
Data Contributor: Pfizer Inc.
Study ID: NCT02928224
Sponsor ID: ARRAY-818-302
A Randomized, Double-blind, Multicenter Phase 3 Study of Irinotecan, Folinic Acid, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab or Placebo in Patients With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine
Data Contributor: Lilly
Study ID: NCT01183780
Sponsor ID: 13856
A Double-blind, Randomised, Placebo Controlled Phase III Study of Nintedanib Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Patients With Metastatic Colorectal Cancer Refractory to Standard Therapies.
Data Contributor: Boehringer Ingelheim
Study ID: NCT02149108
Sponsor ID: 1199.52
A Randomised, Open-label Phase III Study to Assess Efficacy and Safety of Bevacizumab in Combination With Capecitabine as First-line Treatment for Elderly Patients With Metastatic Colorectal Cancer
Data Contributor: Roche
Study ID: NCT00484939
Sponsor ID: MO19286
A Phase III, Multicenter, Randomized, Active-Controlled Clinical Trial to Evaluate the Efficacy and Safety of rhuMAb VEGF (Bevacizumab) in Combination With Standard Chemotherapy in Subjects With Metastatic Colorectal Cancer
Data Contributor: Roche
Study ID: NCT00109070
Sponsor ID: AVF2107g
A Randomized, Open-label Phase III Intergroup Study: Effect of Adding Bevacizumab to Cross Over Fluoropyrimidine Based Chemotherapy (CTx) in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line Standard CTx/Bevacizumab Combination
Data Contributor: Roche
Study ID: NCT00700102
Sponsor ID: ML18147
A Randomized, Three Arm Multinational Phase III Study to Investigate Bevacizumab (q3w or q2w) in Combination With Either Intermittent Capecitabine Plus Oxaliplatin (XELOX) (q3w) or Fluorouracil/Leucovorin With Oxaliplatin (FOLFOX-4) Versus FOLFOX-4 Regimen Alone as Adjuvant Chemotherapy in Colon Carcinoma: The AVANT Study
Data Contributor: Roche
Study ID: NCT00112918
Sponsor ID: BO17920