Precision Medicine Challenge Centralized Pharmacogenomic Recruitment Database

Transcription

1 Precision Medicine Challenge Centralized Pharmacogenomic Recruitment Database March 13, 2016

2 Table of Contents Key Proposal Elements Strategic Considerations Page 2

3 Key Proposal Elements Current Trial Recruitment Process The clinical trial recruitment process is currently not optimized for successful and efficient patient enrollment, particularly for biomarker trials. Clinical Trial Recruitment Flow Pharmaceutical Companies CROs Physicians Patients Key Takeaways The current patient recruitment process proceeds linearly from one stakeholder group to the next An industry sponsor may partner with a CRO or a similar organization to contact hospitals or other physician networks Generally, patients are then informed of and referred to a trial through their own physician This enrollment paradigm is inefficient and imprecise, with approximately 20% of NCTNsponsored trials terminated due to low patient accrual Additionally, 85% of clinical trials are delayed due to recruiting, with ~15% being delayed >6 months Studies that include biomarkers as a part of their enrollment criteria may be at increased risk for early termination due to insufficient patient recruitment Overall, poor enrollment is the most common reason for termination of precision medicine trials (48%) As companies increasingly seek to target genomic and protein biomarkers, efficient identification of these patient subpopulations will likely become critical for precision therapy development Source: Citeline. Recent Trends in Personalized Medicine. 2014; Bennette. J Natl Cancer Inst. 2016; 108 (2):1; Weng. Clin. Research Info. 2012; Covance. Page 3 CRO: Contract Research Organization; NCTN: National Clinical Trials Network.

4 Key Proposal Elements Current Case Studies Inability to efficiently identify and enroll patients has resulted in delayed development or termination of trials for promising future therapies. Poor Patient Identification and Enrollment Leads to Study Cancellations Slow Enrollment Leads to Significant Development Delays After an unsuccessful two-year recruitment period for locally recurrent or metastatic triple-negative breast cancer patients (TNBC), the Phase II trial for the tyrosine kinase inhibitor Tivozanib was terminated in 2014 Although TNBC patients are approximately ~15% of the breast cancer population, AVEO was unable to meet their target recruitment of 30 patients Clinicians perceived that Tivozanib may provide a beneficial effect in TNBC patients, but termination of the trial prevented appropriate clinical validation Phase 1b Trial initiates June 2015 Initial anticipated data release: ~Jan 2016 Updated anticipated data release: Late 2016 A 64-patient Phase 1b trial for a novel RNA-based cystic fibrosis (CF) therapy has been significantly delayed due to slow patient enrollment Despite the prevalence of homozygous ΔF508 CF (~70% CF cases), ProQR cannot efficiently recruit patients from their 22 centers given availability of other therapies A centralized database may allow trial sponsors to directly identify and inform patients of their eligibility in precision therapeutic trials to facilitate trial recruiting, potentially reducing costly delays and trial terminations, and overall delivering precision therapies to patients more rapidly Source: Bennette. JNCI J Natl Cancer Inst. 2016; 108 (2):1; Weng. Clinical Research Informatics. 2012; Covance. Page 4 CF: Cystic Fibrosis; TNBC: Triple-negative Breast Cancer.

5 Key Proposal Elements Overview of Proposed Solution Given the current bottleneck at trial recruitment, we propose creating an opt-in, central database of EHR, genetic, and biomarker information. Proposed Patient Recruitment Flow Key Stakeholders A non-profit group would collaborate with the NIH to create the database with secured patient information jdao Proposed Database Clearinghouse Pharmaceutical Companies 2 Pharmaceutical companies would purchase access to the database, as well as the ability to directly alert eligible patients to their trials 3 Physicians 4 Patients CROs Although CROs are integral to the current clinical trial process, the database may significantly alter their role and responsibilities 3 4 Physicians would be responsible for informing and enrolling patients into the database The database would allow patients to be consistently and fully informed of all relevant trials This novel database would specifically target patients with diseases which may benefit most from our current understanding of precision medicine, such as cystic fibrosis and cancers EHR: Electronic Health Record. Page 5 Key: Significant Role Minor Role

6 Key Proposal Elements Patient and Physician Roles The database would notify both physician and patient about relevant trials, substantially increasing the likelihood that a patient is informed and enrolls. Database Enrollment and Utilization Process Key Insights Step Details Physician Informs Patient of Database The physician explains the database and its benefits, as well as acquires consent from the patient Physician Performs Required Assays If the patient has not already undergone the appropriate biomarker or genetic testing, the physician would perform them Patient Receives Notification of Relevant Trial When eligibility criteria match a patient s genetic, biomarker, and/or EHR profile, the system would alert the patient and physician of the clinical trial Patient Inquires about and Potentially Enrolls in Trial The patient could contact their physician or closest center coordinator to discuss the details of the trial and possible enrollment The database would ensure that patients are aware of all trials for which they are eligible Thus, lack of physician awareness or interest would not prevent the patient from being notified about relevant trials However, the system does not rely solely on patient initiative, as their primary disease manager is also pinged about the trial This dual-notification process may be particularly helpful for rural patients who would be willing to travel for care or for HVPs who may be less familiar with current trials Any additional assays would be reimbursed at ASP, plus a set percentage, during an initial period This payment structure would mitigate physician hesitation and financial burden to patients Page 6 ASP: Average Sales Price; HER: Electronic Health Record; HVP: High Volume Prescriber.

7 Key Proposal Elements Potential Impact Overall, this system would streamline the recruitment process for precision medicine trials and improve patient engagement in personalized care. Pharmacogenomic Database Benefits Accelerated Trial Recruitment Improved Trial Design Increased Patient Engagement Decreased Trial Durations A biomarker database would allow for selective patient recruitment for trials that would have otherwise been delayed or terminated Improved availability of patient data may allow for selection criteria and endpoints tailored to specific personal biomarkers The database connects patients to appropriate clinical trials for their personal condition, empowering them to take ownership of their care Decreased enrollment times for precision medicines may shorten trials, leading to faster development and FDA approvals Measures of success will include the following: Patient enrollment Industry participation Trials recruited for through the database Recruitment success rate for precision medicine trials Time-to-approval for trials conducted through the database Page 7

8 Table of Contents Key Proposal Elements Strategic Considerations Page 8

9 Strategic Considerations Challenges for Implementation This initiative may face practical challenges for implementation, which likely could be mitigated with external investment and partnerships. Challenges for Implementation Patient Participation Investment Costs Other (Privacy, technical barriers) A critical mass of patient enrollment is necessary to incentivize industry participation Improved outreach efficiency may decrease the recruitment efforts required to achieve sufficient trial populations Large-scale outreach and recruitment efforts may leverage similar methodologies employed by the NIH PMI Database development and patient registration may require significant upfront investment Initial costs include coverage for genetic and biomarker testing, enrollment efforts, and IT infrastructure Existing sources of private and governmental support may help achieve sustainable funding Robust privacy protection measures are necessary to maintain patient trust and compliance with privacy regulations There currently exists poor interoperability among EHR and CTMS software platforms The fragmented landscapes for both types of software creates silos of patient data Page 9 CTMS: Clinical Trial Management Software; EHR: Electronic Health Record; PMI: Precision Medicine Initiative.

10 Strategic Considerations Database Composition and Size Initially, the database would be composed of patients who may most benefit from our current understanding of precision medicine. Illustrative Database Composition Key Insights APOE4 Alzheimer s ~50 K patients ΔF508 CF ~500 patients Proposed Database Clearinghouse Example APOE4 Alzheimer's Calculation Prevalence ~1.9 M 25% Willingness ~475 K BRCA 1 Breast Cancer ~5 K patients HER2+ Breast Cancer ~10 K patients 10% Access ~50 K Page 10 Database recruitment efforts would first focus upon diseases, such as Alzheimer's, cystic fibrosis, and other chronic diseases CF: Cystic Fibrosis, These patients would be enrolled in the database throughout their lengthier disease progression, allowing the required critical mass of patients to build Utilizing data from a recent Rock Health survey, we assumed that 25% of patients would be willing to submit their information to the database Regardless of cuts due to access and willingness to share data, the database would establish a representative patient pool for companies to contact Additionally, the database would expand outreach efforts, resulting in more successful and rapid enrollment

11 Strategic Considerations Funding and Administration Governmental and non-profit sources would provide initial funding, while buy-in from industry over time would allow for continued administration Summary of Funding and Administration Initial Funding Longitudinal Administration Long-term Buy-in Initial project support would be provided by governmental organizations, non-profits and select patient advocacy groups This would help establish legitimacy, widespread awareness, and goodwill for the database The governing body of the central database would likely be a blend of public and private entities In particular, partnership with the NIH would allow for synergy in patient enrollment methodology After the central database reaches sufficiency for clinical trial enrollment, industry buy-in would sustain its growth Invested companies would be granted access to the database, and for an additional fee, be able to ping patients and physicians for trial enrollment Page 11

12 Strategic Considerations Other Potential Challenges Other potential challenges include patient privacy concerns and technical design considerations, which may be alleviated through a few key measures. Pharmaceutical Companies Patients Central Database Technical Design Considerations Poor standardization of data and record-keeping across software platforms presents a significant barrier at present Inconsistencies in clinical records may compromise data quality and usability Although full technical interoperability may be challenging in the short-term, the database may leverage existing health information exchange standards (e.g., C-CDA) to extract relevant data Long-term partnerships and collaboration with EHR and CTMS software developers can ensure seamless integration Patient Privacy Concerns Patient confidentiality would be ensured through methods similar to those of the NIH s Precision Medicine Initiative Full transparency regarding data sharing, access, and integrity would allow patients to selectively report personal information to pharmaceutical companies Full trial details would be shared with patients, though patient data would not be made available to pharmaceutical companies until patients consent to the clinical trial Page 12 C-CDA: Consolidated Clinical Document Architecture; CTMS: Clinical Trial Management Software; EHR: Electronic Health Record.

13 Patient Recruitment Strategic Considerations Ultimately, the database would accelerate precision therapy trials through aggregation of relevant patients and increased patient awareness. Summary ILLUSTRATIVE The majority of contacted physicians likely have few eligible precision therapy trial candidates within their broader patient pool However, the central database would be enriched with eligible candidates due to its targeted recruitment of patients with diseases currently at the focus of precision medicine and its extensive collection of biomarker and genetic data In addition to accelerating the clinical trial process, this central database would improve patient pool enrichment, potentially leading to higher success rates for precision medicine trials For example, for a trial with APOE4 Alzheimer's patients, a pharmaceutical company would currently need to meticulously plan which physicians to contact, who each may have a few eligible patients, and then allot significant time for enrollment However, the proposed database would be saturated with APOE4 Alzheimer's patients and allow a company to instantly ping all eligible patients or their caregivers with trial and physician coordinator information The central database could likely also be utilized more broadly, first expanding to encompass more data and diseases relevant to precision medicine and eventually to general applicability for all clinical trials Page 13 Key: Current Proposed Solution