Lead Investigator: James Salsbury, University of Sheffield
Title of Proposal Research: Developing methodology for a delayed treatment effect present in a survival trial
Vivli Data Request: 9422
Funding Source: This work has been supported by a University of Sheffield EPSRC Doctoral Training Partnership (DTP) Case Conversion with Novartis Scholarship [project reference 2610753].
Potential Conflicts of Interest: None
Summary of the Proposed Research:
We are looking at a particular class of survival trials. A survival trial is a clinical trial in which we measure the time to an event, usually death. A two-arm trial is a clinical trial in which we have two groups: a control group and a treatment group. Patients are randomly assigned to each group. Patients in the control group all receive either the current standard of care or a placebo (a non-active treatment). Patients in the treatment group receive the experimental treatment.
We are specially looking at survival trials in which the patients in the control group and treatment group have similar outcomes for the first part of the trial. This period is usually lasts between 3 and 6 months. Sometimes in this period, the treatment has no effect, and then after this period the treatment starts to work. This phenomena is commonly known as a delayed treatment effect (DTE). This effect can be observed in a whole range of disease areas, such as melanomas (skin cancer), non-small-cell lung cancer and advanced renal-cell carcinoma (kidney cancer). As there was approximately 18.1 million new cases of cancer worldwide in 2020, this is clearly a very important area of research.
Traditionally, survival trials are not designed to incorporate a delay in the treatment effect. As a result, current design of such trials have the potential to be underpowered, that means the probability of detecting a difference in the treatments could be lower, as there are not enough patients enrolled. This could potentially mean some trials are declared unsuccessful, even though the drug does actually work. This is clearly bad as we could be denying patients access to effective drugs.
Therefore, we are looking at the design of such trials and seeing whether we can improve the efficiency. This involves asking questions to experts in the field about 1) the length of the delay and 2) how well the treatment may work once it begins to take effect. As such, it would be valuable to have data from real clinical trials in which a DTE has been observed, to test our proposed methodology and ensure its robustness in different contexts.
Requested Studies:
A Phase III, Open Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Compared With a Platinum Agent (Cisplatin or Carboplatin) in Combination With Either Pemetrexed or Gemcitabine for PD-L1-Selected, Chemotherapy-Naive Patients With Stage IV Non-Squamous Or Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02409342
Sponsor ID: GO29431
Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC (CheckMate057)
Data Contributor: Bristol Myers Squibb
Study ID: NCT01673867
Sponsor ID: NCT01673867
Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) (CheckMate 017)
Data Contributor: Bristol Myers Squibb
Study ID: NCT01642004
Sponsor ID: NCT01642004
Trial of Nivolumab vs Therapy of Investigator’s Choice in Recurrent or Metastatic Head and Neck Carcinoma (CheckMate 141)
Data Contributor: Bristol Myers Squibb
Study ID: NCT02105636
Sponsor ID: NCT02105636
Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer
Data Contributor: Bristol Myers Squibb
Study ID: NCT02477826
Sponsor ID: NCT02477826
Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
Data Contributor: Bristol Myers Squibb
Sponsor ID: NCT01844505
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Data Contributor: Bristol Myers Squibb
Study ID: NCT01668784
Sponsor ID: NCT01668784
Nivolumab in Previously Untreated Melanoma without BRAF Mutation
Data Contributor: Bristol Myers Squibb
Study ID: NCT01721772
Sponsor ID: NCT01721772