The 4th of February is recognized around the world as World Cancer Day, and this year’s theme is “Not Beyond Us” which focuses on the positive and proactive approach to cancer and the fact that solutions and treatments do exist – solutions that CROS NT is regularly involved in through the analysis and reporting of crucial clinical trial data from oncology studies.
Cancer is among the 10 leading causes of death in the world and accounts for approximately 8.2 million deaths a year in the U.S. Oncology drug development consumes an average of seven years in clinical evaluation and yields a discouraging success rate: only 7% of oncology agents entering Phase I gain marketing approval.
What makes oncology so unique?
It is not a single characteristic which makes cancer research different, but rather the simultaneous occurrence of:
- Many etiologies
- The importance of disease sub-types and/or genotypes
- The use of treatment combinations
- Different modes of action of drugs
- Regimen modifications during treatment
- The high impact of the disease on patient life
- The high costs of treatment
- Slow recruitment
- Long timelines to reach clinical endpoints
The Role of Biostatistics in Oncology Research
How can a statistician help drug developers focus on the right dose, the right disease in the right patients as early in the research process as possible?
Early Phase Success
Phase I and II product development lays the foundation for successful Phase III studies. Particularly in oncology, the heterogeneity of the disease can influence the planning of clinical trials. New study designs make it possible to minimize the number of patients in the early stages.
The Statistical Analysis Plan for oncology trials, especially for Phase I trials, is extremely important in terms of determining trial design, sample size, endpoints and determining inclusion/exclusion criteria. The biostatistician should be involved in the beginning of an oncolody study to consult on these critical aspects.
Good practice designs in oncology can speed up the planning phase; a team with previous oncology experience will enable a reduction of time from the study synopsis to first patient in the study because it defines adequate target criteria, interim analyses and specifices the most efficient statistical method for analysis.
Late Phase Oncology Study Designs
Given the unique characteristics of oncology trials, Adaptive Trial Design can be an ideal statistical methodology for more efficient, cost-effective trials, especially in Phase III development where efficacy should be confirmed. It allows for the selection of the right target population for the drug. This is of special interest in the development of highly specific cancer drugs, which are only effective in a selected patient population, for example monoclonal antibodies. The advantages of adaptive design for oncology research are a reduction in overall time in the development of a drug, fewer patients required and early availability of long-term safety data.
Clinical Endpoint Considerations
Oncology is also unique in that the time to reach clinical endpoints is longer than other areas. The ultimate endpoint for registration of a new drug is still the “Oveall Survival Time”. Surrogate endpoints like “response rates” or “time to progression” are often used but mostly as secondary endpoints or in earlier phases of the development process.
The long time period before any conclusion from the study can be drawn is the main reason for the use of adaptive designs in this setting. Adaptive design enable researchers to make early decisions on interim analyses such as sample size adjustment or early termination if a study is doomed for failure.
CROS NT and Oncology Research
Oncology is a particular area of expertise for CROS NT, and we have completed over 100 studies in multiple oncology indications from small Phase I trials to large Phase III and IV multinational trials. Our biostatisticians have worked in numerous indications including breast cancer, prostate cancer, colorectal cancer, CML, AML, lung cancer, lymphoma and leukemia.