Regulatory Radar: 21st Century Cures Act, Patient-Focused Drug Development

The 21st Century Cures Act, enacted into law December of 2016, is an initiative to expedite and enhance the process of discovery, development and delivery for disease treatments.

A key feature of this initiative is to redesign the agency's drug evaluation process by integrating each siloed stage into a comprehensive and more efficient cycle. The link completing the cycle is to inform the earlier stages of drug discovery and development with context from the later stages of drug delivery to each unique patient population. This concept is known as Patient-Focused Drug Development and it is integral to the Cures Act, but it is not novel to the pharmaceutical industry or its regulators.

In 2012, the Prescription Drug User Fee Act was reauthorized (PDUFA V), and it incorporated FDA's then new initiative for Patient-Focused Drug Development. This involved gathering patients' perspectives on their condition and available treatment therapies then using the information for context in the FDA review process. In order to collect this information, FDA held public meetings for 24 specific disease areas, which began in 2013 and will conclude in 2017. Each meeting resulted in a unique Voice of the Patient report, summarizing input provided by patients or patient representatives at the disease-specific meeting.

The Cures Act further recognizes the significance of the patient experience surrounding regulatory decisions and expands on the concept of Patient-Focused Drug Development by laying out a framework for its application, guidance and evaluation within FDA. Under Title III: Development, Subtitle A: Patient-Focused Drug Development, the Cures Act breaks down the implementation of Patient-Focused Drug Development into four main sections.

First, it defines Patient Experience Data as data collected by patients, parents, caregivers, patient advocacy organizations, disease research foundations or medical researchers that is intended to provide information about the experience of patients with a disease, or the impact a disease and management of the disease has on the lives of patients or their caregivers. This section also requires FDA to include a statement regarding any Patient Experience Data that was considered at the time the drug is approved.

Second, it requires FDA to develop and issue guidance documents for Patient-Focused Drug Development. This includes guidance regarding the collection of patient experience data and use of the data in drug development and addresses the following:

• Methods to collect patient experience data for submission to FDA and its proposed use by FDA
• Methods that may be used to develop and identify what is most important to patients with respect to burden of disease, burden of treatment and benefits and risks in the management of the patients' disease
• Approaches to identifying and developing methods to measure impact to patients that will help facilitate collection of patient experience data in clinical trials
• Methodologies, standards and technologies to collect and analyze clinical outcome assessments for purposes of regulatory decision-making
• How patients or other persons can develop and submit a draft guidance on this topic for consideration by FDA
• The format and content of patient experience data submitted to FDA
• How FDA will respond to such patient experience data submissions, including any timeframe for response
• How FDA will use relevant patient experience data and related information in structured Benefit-Risk Assessments for regulatory decision-making

Third, it exempts FDA from the Paperwork Reduction Act when requesting information from patients, allowing for a more timely and efficient response.

Finally, it requires FDA to report and publish online its review of patient experience data and information on patient-focused drug development tools as a part of approved drugs no later than June 1 of 2021, with follow-up reports in 2028 and 2031.

Taken together, the Cures Act provides for patient input to be incorporated in a more structured manner into the drug development process and at an earlier stage (clinical trial phase). The framework proposed under the Cures Act will aid in capturing patient experience data in a meaningful way to contribute to the decision making process. Importantly, the patient perspective may influence the drug approval process, potentially shifting the risk-benefit balance towards more risk where patients indicate that they are willing to accept more risk (e.g. the patients' acceptance of potentially undesirable side effects may shift the risk-benefit assessment where patients can more clearly indicate their preference in light of treatment benefits). Finally, the inclusion of the patient voice in the drug evaluation process often seeking faster and earlier approval of new drugs will put extra scrutiny on regulators and their main mission of protecting the public health.

A timeline for what to expect from FDA and when can be found below:

Date of Enactment: December 13, 2016

• June 11, 2017 (180 days): An agenda for when guidance documents must be issued over the next 5 years
• June 13, 2018 (18 Months): At least one draft guidance must be issued*
• June 2021: Report assessing use of PE data in regulatory decision-making
• June 2026: Follow-up report assessing use of PE data
• June 2031: Follow-up report assessing use of PE data

Articles are authored by Marinka Tellier and Andy Papas, at NSF, Pharma Biotech. Do you have any questions? Please reach out to NSF’s experts Marinka Tellier or Andy Papas. Visit our website to learn more about NSF's pharma biotech services.