OCE Scientific Collaborative

The Oncology Center of Excellence (OCE) Scientific Collaborative supports FDA oncology staff who participate in regulatory science research, including internal research projects and collaborations with external experts. OCE research focuses on applied (rather than basic) research questions to address specific challenges encountered during the IND and NDA/BLA review process. The OCE has identified nine scientific interest areas and one cross cutting area for its applied research efforts described below.

OCE engages with external scientists using several approaches including informal collaborations, research collaboration agreements, memoranda of understanding, public-private partnerships, and sometimes provides research funding for these efforts.

OCE uses several mechanisms to fund extramural research, including the FDA Broad Agency Announcement (BAA) and the Centers of Excellence in Regulatory Science and Innovation (CERSI) and OCE-specific funding opportunity announcements. For information on submitting an oncology-related application to the FDA BAA, please review OCE BAA Frequently Asked Questions.

For more information about oncology extramural projects, visit OCE-Funded Active Extramural Research Projects.

OCE also conducts internal research projects, particularly pooled analyses of clinical trial data, that focus on questions emerging from regulatory review include building a deeper understanding of the safety and efficacy of oncology therapeutics as well as generating insights into subpopulations, endpoints, clinical outcome assessment data, and other drug-development issues.

For questions regarding the OCE Scientific Collaborative, contact FDAOncology@fda.hhs.gov

Scientific Interest Areas:

I. Cell/gene and personalized neo-antigen-based therapies for cancer

Cell therapy is a promising new form of cancer treatment as demonstrated by recent CAR T-cell therapy approvals. New technologies are enabling rapid manufacturing of cells with tumor-killing capacity, necessitating more efficient clinical evaluation and innovative regulatory approaches.

The science of neo-antigen-based therapies for cancer is also developing rapidly, particularly since advances in genomics and proteomics allow identification of somatic mutations unique to individual cancers. Recent studies have demonstrated that high levels of somatic tumor mutations are correlated with response to immunotherapies such as checkpoint inhibitors, suggesting that individual tumor mutations (neoantigens) could be harnessed for immune targeting to develop personalized therapies such as cancer vaccines and cell therapies that target these neoantigens.

OCE is interested in supporting research related to clinical development, safety, manufacturing and quality control for cell therapy and neo-antigen-based therapies for cancer. Example OCE research interests in this scientific priority area include:

Create novel technologies and approaches to evaluate both efficacy and safety for neoantigen-based therapies that incorporate unique features of individual cancers, neoantigen and immune responses. Examples may include neoantigen-based vaccines redirecting the T-cell specificity by genetically modifying T cells with receptors specific against neoantigen-derived epitopes. (BAA section I. Modernize development and evaluation of FDA-regulated products, B. Advanced Manufacturing Approaches, 6a.)
Develop, optimize and standardize bioinformatic algorithms for neoantigen identification and development of personalized therapies. These are important to ensure the efficacy and safety of these products in the treatment of patients with cancer. (BAA section I. Modernize development and evaluation of FDA-regulated products, C. Analytical and Computational Methods, 7a.)
Develop innovative trial designs (e.g., master protocols) for a group of cell or neoantigen-based therapies that were developed using a common platform (but target distinct antigens) to compare safety and clinical activity among products to identify the most promising candidates for further development. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 6a.)
Develop innovative clinical trial designs to establish safety and efficacy in cell and gene therapies in randomized clinical studies where feasible. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 6b.)

II. Health equity and special populations in oncology clinical trials

OCE is interested in understanding the factors that affect the safety and treatment response in demographic subgroups that have been historically underrepresented in oncology trials (e.g., racial/ethnic minorities, sexual and gender minorities, older adults). Risk factors, underlying differences in the disease biology, and access to healthcare may vary in these subgroups and impact outcomes in these subgroups. It is therefore critical to obtain information about these special populations to assess whether the evidence generated in clinical trials to support the safety and effectiveness of therapeutics is generalizable to the larger patient population.

Example OCE research interests in this scientific priority area include:

Characterize the prevalence of currently druggable biomarkers in racial/ethnic minorities and assess implications for enrollment in clinical trials. (BAA section I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 6a.)
Evaluate the effectiveness of interventions designed to enroll diverse populations in oncology clinical trials such as digital health (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 7a.)
Understand the impact of remote assessments and decentralized procedures (e.g., e-consent, telemedicine, collecting laboratory and/or imaging data from local facilities) on underrepresented subgroups participating in oncology clinical trials. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 7b.)
Develop framework for assessing clinical site readiness to achieve adequate enrollment of participants from historically under-represented racial/ethnic subgroups in therapeutic oncology clinical trials. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 7c.)
Conduct qualitative research to perform root cause analysis to understand barriers to including underrepresented subgroups in oncology clinical trials (e.g., access to clinical trial sites, patient and/or physician preference, and/or other structural, operational or trial-specific barriers), not previously reported. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 7d.)
Identify best practices for enrolling underrepresented subgroups in oncology clinical trials, including patient-, physician-, and community-focused approaches, not previously reported. . (I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 7e)
Identify best practices for data collection to characterize the experience of persons who are members of sexual and gender minority groups, in cancer clinical trials (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 7f.)
Identify best practices to conduct multi-regional cancer clinical trials in regions of the world not traditionally represented in global cancer trials (e.g., Africa, Central America, South America). (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 7g.)
Applied research to improve the understanding of the pathophysiologic process of cancer in members of underrepresented minority groups that can have a practical impact on oncology drug development. (BAA section I. Modernize development and evaluation of FDA-regulated products, G. Predictive Toxicology, 3a.)
Applied research addressing clinical pharmacology assessment in underrepresented populations (e.g., pharmacokinetic, pharmacodynamic and/or pharmacogenetic analyses) that can have a practical impact on oncology drug development. (BAA section I. Modernize development and evaluation of FDA-regulated products, G. Predictive Toxicology, 3b.)
Conduct RWD studies to improve understanding of safety and efficacy, for example through analyses of low grade toxicities or symptom function measures in underrepresented subgroups. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 9a.)
Study RWD to understand patterns of care and clinical outcomes in sexual and gender minorities with cancer. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 9b.)

III. Immuno-oncology

Immune checkpoint inhibitors (ICI) have become the standard of care for multiple types of cancer and offer long-term disease control often with fewer (albeit unique) side effects compared to those encountered with chemotherapy. As the number of clinical trials evaluating ICIs either as single agents or in combination for the treatment of patients with cancer continues to increase, standardized approaches for predicting, identifying, and reporting side effects of ICIs becomes increasingly important.

Additionally, a large proportion of patients do not respond or become resistant to these treatments. There is a high unmet need to develop therapeutics for ICI-refractory or resistant patients, yet the field lacks a consistent definition of response for these drugs. Response is well defined for cytotoxic drugs and targeted therapies using images analyzed by response evaluation criteria in solid tumors (RECIST) criteria v 1.1; however, RECIST analyses reveal that a considerable proportion of patients treated with ICI demonstrate late response or may show initial-- potential accelerated--tumor growth that can be followed by tumor shrinkage. These atypical response patterns complicate FDA’s ability to provide advice to sponsors about clinical trial design.

Example OCE research interests in this scientific priority area include:

Perform analyses of clinical data to develop a better understanding of the proportion of patients with atypical response and/or resistance and explore the development of predictive analytic approaches to identify patients who will eventually respond to ICI treatment from those who will not respond. (BAA section I. Modernize development and evaluation of FDA-regulated products, C. Analytical and Computational Methods, 6a.)
Develop biomarkers and/or pharmacodynamic endpoints to demonstrate the effect of ICI in cancer immunotherapies or as part of a combination regimen in treatment-naïve and immune resistant settings. (BAA section I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 3a.)
Develop technologies and approaches that better predict or characterize atypical response patterns to IC such as radiomics, circulating tumor DNA, and/or novel approaches for immune cell profiling of the micro-environment. (BAA section I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 3b.)
Support research in two areas to improve understanding of the side effects of ICIs. (BAA section I. Modernize development and evaluation of FDA-regulated products, E. Clinical Outcome Assessment, 5a.)
Develop clinical trial endpoints that can help capture atypical response patterns to more fully characterize the clinical benefit of ICI and other cancer immunotherapies. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 5a.)
Develop clinical trial designs that can help capture atypical response to ICI and other cancer immunotherapies and can facilitate therapeutic development in immunotherapy resistant settings. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 5b.)
Research that can improve prospective planning of clinical trials and analysis in the presence of non-proportional hazards for time-to-event endpoints (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 5c.)
Analyze RWD to understand the utilization of complementary in vitro diagnostics and impact on utilization of cancer immunotherapy as a single agent or as part of a combination regimen. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 8a.)

IV. Oncology patient-focused drug development

Cancer patients experience disease symptoms and symptomatic treatment side effects that can impact their ability to function and other aspects of their health-related quality of life. OCE is interested in supporting research focused on developing approaches to assess the patient experience that will complement existing survival and tumor information.

Symptomatic adverse events and overall side effect impact are critically important to patients and improved analysis and visualization of symptomatic adverse events is a priority. In addition, the OCE is interested in exploring the utility of a single overall side effect global impact question that can be used to summarize overall side effect burden.

Physical function is another important patient-centered outcome that is a focus area of OCE research efforts. In particular, OCE is interested to learn more about the impact of different technologies, recall periods and different data collection platforms for gathering physical function data in oncology clinical trials.

FDA has identified the use of electronically captured patient-reported outcome (ePRO) physical function scales and wearable technologies as promising drug development tools to inform future development of oncology clinical trial endpoints. OCE is interested to understand the impact of using different measurement techniques on assessing physical function in a prospective natural history study of advanced cancer, particularly (1) wearable technologies (e.g., MIT E4 watch, actigraph accelerometer); (2) electronically captured patient-reported approaches (e.g., PROMIS ® physical function item bank) and (3) traditional clinician-based assessments (e.g., ECOG or Karnofsky performance status) and performance outcomes (e.g., 6-minute walk test or other PerfO). The research would analyze these data sources and their association with global anchor questions and other important clinical events such as hospitalizations, treatment changes, concomitant/supportive medication use and palliative procedures and survival.

Example OCE research interests in this scientific priority area include:

Investigate the sensitivity and measurement characteristics of existing patient-reported physical function measures in patients with rare and ultra-rare cancers. (BAA section I. Modernize development and evaluation of FDA-regulated products, E. Clinical Outcome Assessment, 3a.)
Investigate open label bias: evaluate the impact of patients knowledge of their treatment on patient-reported outcomes in cancer clinical trials. (BAA section I. Modernize development and evaluation of FDA-regulated products, E. Clinical Outcome Assessment, 3b.)
Evaluate differences in measurement characteristics between core patient-reported outcomes collected in US versus ex-US oncology patient populations. (BAA section I. Modernize development and evaluation of FDA-regulated products, E. Clinical Outcome Assessment, 3c.)
Study existing methods and develop novel methods to measure patient-reported symptomatic ocular toxicity in patients receiving anti-cancer therapy (BAA section I. Modernize development and evaluation of FDA-regulated products, E. Clinical Outcome Assessment, 3d.)

V. Oncology safety

Many advances have been made in the treatment of cancer with an increasing number of treatment options available to oncology patients. With the introduction of newer treatment approaches, little is known about the differential rate and severity of side effects and toxicities. Many cancer patients are living longer but at the same time they are experiencing an increase in symptom burden due to exposure to multiple lines of cancer therapy.

Some toxicities are acute while others become chronic. Often, the extent of the toxicity burden is unknown until the drug is administered to a large population of 'real-world' patients with comorbidities that were not included in a clinical trial, or until long-term follow-up uncovers late-onset toxicities. The natural trajectory, as well as the underlying mechanisms of many toxicities, is not well understood. There are no clear predictors of who may experience these symptoms and toxicities and why they vary in severity and duration from one individual to another.

For most of the toxicities caused by cancer treatment, no approved mitigating therapies or evidence-based management strategies are in place. There is a lack of mechanistic insight into these adverse events, difficulties in objectively measuring treatment-related toxic effects and insufficient studies validating pre-clinical biomarkers in the clinical setting.

Example OCE research interests in this scientific priority area include:

Develop improved and standardized approaches to collect and analyze cardiotoxicity data in the context of clinical trials to support new indications. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 5a.)
Develop approaches for collecting medical product safety data from RWD sources to expand understanding of the safety profile of approved oncology products in clinical practice. (BAA section II. Strengthen post-market surveillance and labeling of regulated products A. Methodologies to Assess Real-World Data (RWD) to serve as Real-World Evidence (RWE), 4a.)
Conduct analyses using RWD sources with a history of or active COVID-19 infection to evaluate increased severity of known drug adverse reactions or new toxicities, longitudinal sequelae, and residual toxicity. (BAA section II. Strengthen post-market surveillance and labeling of regulated products A. Methodologies to Assess Real-World Data (RWD) to serve as Real-World Evidence (RWE), 4b.)
Analyze RWD to help understand which patients are most likely to experience cardiotoxicity (or other types of severe toxicity) during cancer treatment. (BAA section II. Strengthen post-market surveillance and labeling of regulated products A. Methodologies to Assess Real-World Data (RWD) to serve as Real-World Evidence (RWE), 4c.)
Develop improved and standardized approaches to collect and analyze cardiotoxicity data in the context of post approval clinical trials and clinical practice. (BAA section II. Strengthen post-market surveillance and labeling of regulated products C. Novel Clinical Trial Design, Statistical and Epidemiologic Methods, 2a.)
Conduct basic, translational or clinical studies that investigate the underlying causes of cardiac toxicities associated with approved oncology agents. (BAA section II. Strengthen post-market surveillance and labeling of regulated products C. Novel Clinical Trial Design, Statistical and Epidemiologic Methods, 2b.)
Develop novel approaches to utilizing AI/ML to mine different data sources (e.g., EHRs, claims data, clinical trial data) for safety signal identification and/or characterization of oncology therapeutics. (BAA section II. Strengthen post-market surveillance and labeling of regulated products C. Novel Clinical Trial Design, Statistical and Epidemiologic Methods, 2c.)
Develop models and/or new translational study designs to better understand the mechanisms of toxicity underlying causes of recent safety alerts issued by FDA oncology. (BAA section II. Strengthen post-market surveillance and labeling of regulated products C. Novel Clinical Trial Design, Statistical and Epidemiologic Methods, 2d.)
Develop tools and/or algorithms to identify adverse reactions such as cytokine release syndrome, or other immune-related adverse events to eliminate the need for manual adjudication (BAA section II. Strengthen post-market surveillance and labeling of regulated products D. Automated Reporting Tools for Adverse Events and Active Surveillance, 4a.)

VI. Oncology trial designs, endpoints and statistical methodologies

OCE provides detailed advice to sponsors about appropriate clinical trial designs, including statistical analysis methods. Rapid technological developments in electronic capture of medical record and claims data has increased sponsors’ interest in using data sources other than information collected during traditional clinical trials to support regulatory submissions.

OCE is also interested in research to define and validate real world endpoints that can be collected from Electronic Health Records (EHR) and how real world endpoints perform relative to traditional endpoints used in clinical trials to support regulatory approval oncology products, such as Overall Response Rate, Progression Free Survival, and Overall Survival. Collecting traditional oncology endpoints is labor-intensive and normally only performed in the context of a clinical trial, so it is unclear whether data collected during the course of clinical care will provide comparable information.

Example OCE research interests in this scientific priority area include:

Develop novel statistical approaches for using external controls in oncology trials, which could supplement concurrent control arm data and address key challenges such as differences in eligibility criteria, exposure and outcomes between external control and clinical trial patients; bias, and rapidly evolving standards of care. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 3a.)
Develop statistical methods to assess bias and misclassification when RWD is used in estimating treatment effect. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 3b.)
Multi-disciplinary research that includes expert clinical and statistical input addressing how external control data can be used as supportive data to isolate the treatment effect of experimental combination therapies. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 3c.)
Develop innovative clinical trial designs to find the optimal dose for oncology therapeutics. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 3d.)
Research relating to the design and analysis of pragmatic trials, for example using cluster randomization techniques (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 3e.)
Develop statistical methods for ruling out detrimental treatment effects on overall survival in clinical trials of indolent cancers. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 3f.)
Develop innovative clinical trial designs to find the optimal dose for oncology therapeutics.

VII. Pediatric oncology

The development of drugs for children with cancer involves unique biological, clinical, societal and economic challenges. Pediatric drug development usually leverages efforts in adult drug discovery and development. Recent observations made possible through large scale pan-cancer genomic profiling across multiple pediatric cancers suggest that more than 50% of childhood cancers express druggable (approved, targeted drugs available) molecular aberrations. However, some targeted agents developed for adults are not effective in children. For example, immune checkpoint inhibitors have transformed treatment for several adult cancers; however, these drugs are less effective in pediatric cancers because of diminished neoantigen expression due to low mutational burdens. The lack of pre-clinical testing in pediatric tumors is also a major obstacle to advancing the field and is critical to identify promising molecular targets for pediatric cancers.

Example OCE research interests in this scientific priority area include:

Development of immune based therapies (engineered immune effector cells or bifunctional activators) that recognize tumor specific altered glycan epitopes (glycolipids or glycoproteins) that NK and T-cells do not generally recognize. (BAA section I. Modernize development and evaluation of FDA-regulated products, B. Advanced Manufacturing Approaches, 7a)
Development of preclinical models (e.g., patient-derived xenograft models, orthotopic mouse models, organoids) of pediatric tumors to facilitate decision-making regarding the evaluation of emerging novel agents potentially applicable to tumors which predominantly occur in the pediatric population. (BAA section I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 5a)
Investigations using text mining and/or artificial intelligence to analyze, assess and interpret the scientific literature and other public databases of genomic and transcriptomic analyses of pediatric cancers to (1) identify drugs that have been used against molecular targets relevant in pediatric cancers and/or (2) elucidate the relevance of specific molecular targets to the growth and/or progression of pediatric tumors to understand and assess target actionability. (BAA section I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 5b)
Investigations to solicit children’s self-report of treatment related adverse events to accommodate the child’s voice in assessing patient tolerability of new drugs.(I. Modernize development and evaluation of FDA-regulated products, E. Clinical Outcome Assessment, 6a)
Evaluate, (in collaboration with statistical experts) novel study designs for small populations including Bayesian approaches to borrowing from adult data and relaxed type 1 error considerations to facilitate randomized trials whenever possible. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 4a)
Translational research to design and develop rational combination regimens for pediatric patients that may include ICIs and other treatments (e.g., chemotherapy, vaccines, radiation) based on a strong scientific rationale that addresses the current data suggesting lack of activity of single agent ICIs in pediatric tumors. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 4b)
Investigations to explore opportunities to develop acceptable external control arms from RWD to aid in accelerating new drug approvals for childhood cancer. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 6a)

VIII. Precision oncology

Implementation of precision oncology has grown rapidly in recent years, with dozens of gene- and protein-based markers used to define enrollment criteria for oncology clinical trials and included in drug labels as companion or complementary diagnostics, pharmacogenomic or safety markers. There is a continued need to further understand the role of different biomarkers in oncology including identifying groups of patients who respond (or do not respond) to different treatments, better understanding disease progression and resistance mechanisms, and identifying high risk populations.

Several exciting technologies are advancing precision oncology, including measuring molecular changes in circulating tumor DNA isolated from plasma, and radiomics, an emerging science that uses algorithms to extract features from medical images that are invisible to the human eye. Combined with advanced machine learning algorithms, radiomics can improve disease detection, characterization, staging, as well as assessment and prediction of treatment response. A related field, radiogenomics, assesses the relationship between imaging features and gene expression. Work in this area is advancing rapidly since extensive imaging and genomic information are routinely collected in oncology clinical trials.

Example OCE research interests in this scientific priority area include:

Develop novel selection/response biomarkers using algorithms combining different types of medical images including radiology images (e.g., CT, PET) and/or histopathology images combined with novel analysis approaches such as radiomics and artificial intelligence/machine learning. (BAA section I. Modernize development and evaluation of FDA-regulated products, C. Analytical and Computational Methods, 8a)
Identify and explore approaches to validate biomarkers (including liquid biopsy biomarkers) for escalation/de-escalation of treatments in the neoadjuvant, adjuvant and advanced disease settings. (BAA section I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 4a)
Conduct studies to compare the analytical and clinical performance of local and centralized molecular tests used for patient enrollment on cancer clinical trials. (I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 4b)
Conduct studies to understand why tumors located at different organ sites with molecular alterations in the same target respond differently to therapies to inform future potential tumor agnostic drug development. (BAA section I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 4c)
Conduct retrospective or prospective studies/biomarker evaluations to understand if there are differences in response to targeted cancer treatment based on somatic vs. germline alterations of the target gene. A particular area of interest is to improve understanding of any differences in activity of PARP inhibitors in patients with BRCA mutations vs. other individual homologous recombination repair (HRR) mutations. (BAA section I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 4d)
Develop methodologies to assess RWD as supportive evidence generation (clinical trial design; use of real world data for liquid biopsy diagnostics that are assessing multiple cancer types simultaneously for early detection indications (multicancer early detections; [MCED]) along with the data from prospective clinical studies that are needed as clinical validation for MCED assays. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 7a)
Studies, including registries, to understand the epidemiology and rates of biomarker testing in patients with cancer, such as studying the prevalence of rare genomic subsets of clinical interest in patients with cancer. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 7b)

IX. Rare cancers

Identifying candidate drugs and testing their effects in rare populations can be challenging and time consuming. Investigating approved drugs potentially offers a more efficient pathway for drug development for rare cancers. Telemedicine is also an area of interest for OCE, as it has been a successful tool for clinical trials and patient care in other disease areas (e.g., stroke, Parkinson’s disease), but has not been widely implemented in oncology.

OCE is interested in supporting research to assist drug development for rare cancers, defined by the Orphan Drug Act as a disease or condition that affects fewer than 200,000 people in the U.S. and includes several molecularly-defined subsets (e.g., RET-positive lung cancers) and all pediatric cancers such as:

Investigations using text mining and/or artificial intelligence to analyze, assess, and interpret the scientific literature and other public databases of genomic and transcriptomic analyses in rare cancers to identify drugs that have been used against molecular targets relevant in rare cancers. (BAA section I. Modernize development and evaluation of FDA-regulated products, C. Analytical and Computational Methods, 9a)
Investigations to characterize the plasma membrane surface-ome of health cells/tissues and ultra-rare tumors such that logic gated CAR-T cell therapeutic approaches can be encouraged, and potential on-target, off-tumor safety issues can be identified. (BAA section I. Modernize development and evaluation of FDA-regulated products, C. Analytical and Computational Methods, 9b)
Innovative approaches to identify new biologically-driven opportunities for clinical development of previously approved drugs (or drugs for which development has been discontinued) in rare cancers. (I. Modernize development and evaluation of FDA-regulated products, D. Biomarkers, 7a)
Studies to develop and characterize symptom function measures for rare cancers to complement information obtained from traditional clinical trial endpoints used in regulatory submissions. (BAA section I. Modernize development and evaluation of FDA-regulated products, E. Clinical Outcome Assessment (COA), 4a)
Studies in rare cancers incorporating use of telemedicine and/or decentralized approaches (e.g., collecting laboratory and/or imaging data from local facilities) for patient assessments to facilitate enrollment of patients with rare cancers. (BAA section I. Modernize development and evaluation of FDA-regulated products, F. Complex and Novel Clinical Trial Design, 8a)
Studies, including registires, to investigate the natural history of rare cancers to provide clinical and scientific context to inform the design and interpretation of clinical trials. This work could involve analyses of registries and/or other RWD. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 10a)
Investigations to explore opportunities to develop appropriate external control arms using real world evidence or clinical trial data to support the clinical development of new drugs for rare cancers. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 10b)

Cross Cutting Area:

Oncology Real World Data and Real World Evidence

Developing approaches to evaluate, integrate, and facilitate the use of oncology real world data (RWD) (e.g., electronic health records, administrative health claims, drug or disease registries, patient reported or generated health data) to generate high quality real world evidence (RWE) is an active area of regulatory science as noted in the 21st Century Cures Act.

Methodologically rigorous research which expands upon the need to evaluate innovative study approached such as Pragmatic Clinical Trials, or other prospective designs including development of RWD resources through high quality registry studies to accelerate clinical development of new drugs in oncology are encouraged. Specific examples of interest are included in the immuno-oncology, health equity and special populations in oncology drug development, oncology trial designs, endpoints and statistical methodologies, pediatric oncology, oncology safety, and rare cancers sections of this document. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 4a.)

Evaluation of innovative applications of RWD to clinical drug development, including epidemiologic and statistical approaches, specifically through scientific methods research to enhance evaluation and assessment of RWD through evaluation of bias, confounding, or other potential threats to study validity. Examples include investigations to explore appropriate uses of externally controlled designs in clinical drug development. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 4b)
Explore and define RWD quality through a research study or framework development fo consider factors including data reliability and relevance including (but not limited to) factors such as collection missingness, specificity, sensitivity, data validation, data harmonization, data provenance, interoperability, data linkage, and the potential capability to make accurate inferences from the available data or improve standardization efforts in the source data towards learning healthcare systems. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 4c)
Methods-focused research using artificial intelligence to analyze, assess and interpret the scientific literature and RWD to enhance understanding for potential uses in regulatory science. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 4d)
Develop, define and test real world oncology endpoints from RWD that could be used to generate real world evidence (RWE) to complement traditional clinical trial data submitted to FDA, particularly the development of measures of real world response. (BAA section I. Modernize development and evaluation of FDA-regulated products, J. Methods to Assess Real-World Data to serve as Real-World Evidence, 4e)

U.S. Food and Drug Administration

OCE Scientific Collaborative

Further Information