In 2022, the OCE Patient Focused Drug Development (PFDD) Program continued to advance its mission of incorporating patient experience data, including rigorous assessment of patient-reported symptoms and function into oncology drug development and regulatory decision making.

Engagement and Education:

• In collaboration with Project Community, in March 2022, the PFDD program held a Conversations on Cancer public panel discussion on understanding cancer treatment tolerability.
• The program held its seventh annual Clinical Outcomes Assessments in Cancer Clinical Trials workshop in June 2022. This year’s workshop discussed the realities, analysis, and interpretation of PROs in open-label trial designs and reiterated the value of PROs across different trial designs, particularly when used to inform tolerability, and in early-phase clinical trials.   
• The PFDD team also presented at 11 external workshops and conferences over the past year on a variety of topics including, FDA patient engagement, patient-centric exposure-response analyses, and PROs in clinical trials to inform decision-making

Regulatory and Policy:

• This year, the program continued providing expert consultation to FDA centers and review divisions for scientific regulatory review and advice on  collection and analysis of patient generated data in over 100 oncology product meetings and applications.
• In conjunction with Project Optimus, the PFDD program encouraged integration of the patient-experience in early phase product development. This included participation in public workshops, academic conferences, and multi-stakeholder publications.

Research and Science:

• In the fall of 2022, the PFDD program funded two new collaborations with Yale-Mayo Clinic to define meaningful within-patient change in symptoms of advanced cancer, and develop longitudinal analyses and visualizations of patient-reported physical function and symptom data in cancer.
• Including the new projects above, the program has funded over 4 million dollars for research studies measuring patient-reported symptoms, physical function, and overall side effect bother.
• The program also maintains consistent involvement in cross-governmental and international working groups and consortium to advance the science of PROs in oncology.

The Oncology Real World Evidence Program expanded its role in supporting collaborative review of medical product submissions containing real-world data across FDA centers. The program provided advice on development plans from the IND phase through to NDA and BLA submissions as well as providing pharmacoepidemiologic expertise for Oncologic Drugs Advisory Committee meetings.

The epidemiologic review of real-world data was included in two recent oncology approvals:

• Abatacept was approved December 15, 2021, as the first treatment for the prophylaxis of acute graft versus host disease in combination with CNI and MTX, in patients >2 years of age undergoing HSCT from a matched or 1 allele-mismatched unrelated donor.
• Alpelisib received accelerated approval on April 5, 2022, for the treatment of patients >2 years of age with severe manifestations of PIK3CA-Related Overgrowth Spectrum who require systemic therapy. 

The Oncology RWE team published five journal articles and provided education and engagement through presentations at many professional society annual meetings and conferences. 

In 2022, the OCE’s Project Catalyst continued to provide guidance and expanded the educational resources available to small pharmaceutical companies and academic life science incubators to support informed anticancer therapy development, including:  

• Posting new resources and links for its educational initiative, Oncology Regulatory Expertise and Early Guidance (OREEG), a self-directed platform providing early-stage oncology companies with product-type advice to inform sound product-specific drug development decisions. This platform contains “bench-to-bedside” chats with regulatory science experts focusing on various oncology related drug development issues. 
• Interacting closely with the National Cancer Institute, participating in the CARES program (Connecting Awardees with Regulatory Experts) to provide the NCI Small Business Innovation Research funded companies access to regulatory expertise
• Implementing the OCE Academic Incubator Discussions (AID) Program that allows investigators to receive informal regulatory and scientific discussion on their early drug development plans. OCE has conducted two AID meetings with National Cancer Institute designated academic accelerators in 2022. 
• Planning to integrate the Pre-Pre-IND process, established with the passage of PDUFA VII, into the ongoing OREEG program to provide advice in the earliest stages of sponsor development.  
• Initiating early discussions with stakeholders, in collaboration with the OCE Pediatric Oncology and Rare Cancers Program, to develop a National Cancer Accelerator and Innovation Network (NCAIN) initially focused on ultra-rare cancer.   

Project Catalyst welcomes questions regarding oncology drug development plans that are premature for a pre-IND submission, and values input regarding other efforts that would be useful to early-stage oncology drug development programs. 

In 2022, Project Equity was lead author of the FDA draft Guidance, Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials, a cross-center guidance that provides recommendations to sponsors on the development and submission of diversity plans to the FDA.

Project Equity conducted outreach and engagement activities to promote OCE’s priorities on diversity, obtain feedback from stakeholders on its diversity agenda, and inform OCE’s policy discussions and activities on the topic. This work resulted in co-authorship in eight peer-reviewed publications, two symposia, and 36 invited external speaking opportunities with audiences that included members of academia, pharmaceutical industry, patient advocacy, and other regulatory authorities.  

Project Equity also led efforts to ensure that that regulatory review documents reflect an emphasis on diversity. To that end, Project Equity revised review templates for marketing application reviews and the ODAC meeting briefing documents. Through a consultative process, Project Equity provides input to review divisions on the development of post-marketing study requirements and commitments, to help ensure the study populations enrolled are reflective of the diversity of the population with the disease.  

In 2022, Project Optimus highlighted the importance of dosage optimization to patients by taking part in an OCE Conversations on Cancer entitled “More Isn’t Always Better: Understanding Cancer Treatment Tolerability.” Dosage optimization focuses on safety and tolerability, and Project Optimus collaborated closely with OCE’s Patient Focused Drug Development Program to identify opportunities to incorporate patient-reported outcomes (PRO) to provide a systematic and quantitative assessment of expected symptomatic adverse events and their impact on function. 

Project Optimus expanded efforts to engage with key stakeholders on dosage optimization by planning sessions at the AACR Annual Meeting, ACCP Annual Meeting, ACoP, ASA Biopharmaceutical Section Statistics Workshop, and SITC Annual Meeting. Project Optimus partnered with ASCO to lead a public workshop entitled “Getting the Dose Right: Optimizing Dose Selection Strategies in Oncology,” which featured multi-stakeholder discussions on strategies to achieve dosage optimization and was attended by approximately 2,000 participants. 

Project Significant (Statistics in Cancer Trials) continued its discussion series with the Biopharmaceutical Section of the American Statistical Association and oncology stakeholders to further the design and analysis of cancer clinical trials. In 2022, the project published six articles based on its panel discussions. Key topics included: 

Bayesian approaches in pediatric cancer trials—The main takeaway of the panel discussion was the recognition that while standard frequentist approaches to randomized controlled trials are the preferred approach, in rare diseases such as pediatric cancers, such trials may not be feasible. Bayesian and other innovative approaches are needed to advance treatment in pediatric cancers.   

Statistical methods for evaluating treatment effects of time-to-event outcomes in cancer trials in the presence of non-proportional hazards—The panel discussion addressed the challenges of pre-specification, how to choose an appropriate statistical method, and how the results are interpreted when NPH is observed in cancer clinical trials that are intended for regulatory decision making. Adequate follow-up and number of events are critical in establishing treatment effect when NPH is observed.  

Impact on Type I Error with unplanned analyses in cancer trials—Panelists agreed that unplanned analyses should be avoided, but when they are conducted, better transparency on why, what, and how is needed.  

Statistical Considerations in the Evaluation and Interpretation of Interim Overall Survival Results in Patients with Chronic Diseases from Randomized Cancer Clinical Trials—This forum discussed quantifying uncertainty in the evaluation and interpretation of early OS analysis in cancer trials that evaluate treatments for patients with chronic diseases that are intended to support regulatory approval.  Highlights of the discussion included: examining cause of death is always important as early patterns consistent with a detrimental OS effect may disappear as the trial continues; A Bayesian framework might be useful to interpret the available data; Longer follow-up and continued data collection can help in reducing uncertainty of the findings.  

Considerations for Data Monitoring Committee and Regulator Direct Interactions in Ongoing Randomized Cancer Clinical Trials—Multi-disciplinary experts explored when and how communication between DMCs and Regulators. In order to maintain the integrity of the ongoing randomized trial and not jeopardize completion of the trial, prespecifying when and how to communicate between DMC and regulators in the DMC charter is important; however, it may be challenging to prespecify as the circumstances for such interactions may be unanticipated.  

Considerations in the evaluation of progression-free survival with informative censoring in cancer clinical trials—Panelists discussed how to assess impact of informative censoring on the treatment effect estimate. Understanding the reasons for censoring and the censoring patterns in both the treatment and control arms, and potential subgroup-treatment interactions are important in interpreting the treatment effect.  

Assessing Bias in Cancer Studies with Real World Data Elements—Panel discussion highlighted importance of understanding source of external data and whether the available data fit the purpose to answer the research question. Currently RWD has been used only as supportive data in the evaluation of treatments in cancer patients.  

Considerations of innovative cancer clinical trial designs for post-market dose-optimization studies—The discussion highlighted that use of flexible adaptive designs with a Bayesian inference framework and using all available information may be useful in this setting.