BACKGROUND: Evaluating safety risks for pharmaceutical products is challenging. For events with a frequency >1%, a nested case-control approach in an ad hoc cohort is a reasonable alternative. After launch of IressaTM (gefitinib) in Japan, ILD was reported among treated non small-cell lung cancer (NSCLC) patients at a rate of up to 6% within the first months after treatment.
OBJECTIVES: To share study design insights from an ongoing epidemiologic investigation undertaken by AstraZeneca in Japan to estimate the relative risk of ILD among NSCLC patients treated with Iressa vs. other treatments, and elucidate mechanisms and risk factors of ILD.
METHODS: A cohort of NSCLC patients was recruited at 70 Japanese hospitals. Patients receiving Iressa or other treatment were followed for 12 weeks for ILD outcome. For each ILD case identified, 4 controls were sampled from the cohort and detailed information was collected on these subjects. ILD diagnosis was supported by a diagnostic algorithm. A case review board reviewed all identified cases and an external epidemiology advisory board supervised the scientific content of the study. Studies of genetics, proteomics and pharmacokinetics were included, in collaboration with external researchers.
RESULTS: Setting up the study was challenging since clinicians today often are not familiar with epidemiologic designs. Close collaboration between Pharma, Academia and physicians, and across specialties (epidemiology, clinical medicine, genetics, proteomics, clinical pharmacology etc) is required. High participation is a challenge, particularly with biomarker collection, an important component but one that adds complexity. Further recruitment data, descriptive analyses and other lessons will be presented.
CONCLUSIONS: Large prospective epidemiologic studies can be successfully undertaken by a pharmaceutical company. The nested case-control design is useful provided a suitable cohort can be identified or established and the outcome is not too rare. Motivating all participating specialties to work together on an unfamiliar epidemiologic study design is key to success. Support by an external epidemiology advisory board is very helpful.
