Resources

FDA is open to receiving all ideas for questions that can be addressed by pooled analyses of oncology clinical trial data. OCE has outlined scientific interest areas on its OCE Scientific Collaborative website, but is also open to suggestions for research questions addressing other topics. Example topics include:

  • Investigating the relationship patient reported outcomes and clinical benefit

  • Exploring the relationships between different endpoints and those used for oncology regulatory approvals

  • Investigating prognostic and predictive biomarkers

  • Exploring novel statistical analysis methods for clinical trials

Examples of previous pooled analysis research studies in oncology led by FDA staff include:

Efficacy-related studies

  • FDA scientists conducted pooled analyses of patient-level data from seven phase 3 randomized breast cancer trials of CDK inhibitors plus endocrine therapy to investigate the benefit of adding CDK inhibitors to endocrine therapy in patients whose tumors might have differing degrees of endocrine sensitivity. PMID: 31859246

  • FDA scientists completed a pooled analysis of seven trials of metastatic or locally advanced urothelial cancer that led to approval of an anti-PD-1/L1 antibody to explore any relationships between response rate, overall survival, and the related adverse events of special interest or related immune-mediated adverse events. This is an interesting question because the immune mechanism of anti-PD-1/L1 antibody could lead to both tumor response and autoimmunity PMID: 31116675

Studies to explore external controls

  • FDA scientists pooled patient-level data from five randomized trials supporting drug approval in adjuvant HER2-positive early breast cancer to explore whether external controls can contextualize single-arm studies to add to clinical decision making in the use of de-escalated therapy in patients with low-risk HER2-positive early breast cancer. PMID: 32866625

Studies to explore relationships among clinical endpoints

  • FDA scientists conducted pooled analyses of patient-level data from 14 randomized controlled trials submitted to FDA treated with an anti-PD-1 or PD-L1 antibody to explore the performance of iRECIST vs. RECIST V.1.1 PMID: 32107275

  • FDA scientists conducted two separate pooled analyses of two randomized controlled trials of an ALK inhibitor and two RCTs of an anti-PD-1 antibody to explore the association between, depth of response with overall survival (OS) and progression-free survival (PFS) for patients with NSCLC. PMID: 29045514

Studies of underrepresented groups and special populations in oncology clinical trials

  • FDA scientists completed a pooled analysis of five clinical trials of immunomodulatory imide drugs and proteosome inhibitors submitted to FDA for patients with newly diagnosed multiple myeloma (who were not transplantation eligible) to explore the levels of participation among different racial and ethnic groups and investigate any differences in survival among these groups. PMID: 29365319

  • FDA scientists pooled data from four randomized clinical trials comparing PD-1 or PD-L1 treatment to docetaxel for the treatment of patients with advanced or metastatic NSCLC (with disease progression on or after a platinum-containing therapy) to conduct a meta-analysis to investigate efficacy among different age groups. This is an important question because approximately 70% of newly diagnosed NSCLC patients are older than 65 and more than half of these older patients have metastatic or locally advanced disease. PMID: 30391014