Under the 21st Century Cures Act, the FDA is required to develop guidance documents on how to collect and utilize patient experience data in drug development. The agency has published a plan for the timing and focus of the required guidance documents, described below:
|Due Date||Draft Guidance Title (or Topic)|
|End of FY 2018||Patient-Focused Drug Development: Collecting Comprehensive and Representative Input|
|End of FY 2019||Processes and methodological approaches to development of holistic sets of impacts that are most important to patients|
|End of FY 2020||Approaches to identifying and developing measures for an identified set of impacts (e.g., burden of disease and treatment), which may facilitate collection of meaningful patient input in clinical trials|
|End of FY 2021||Clinical outcome assessments, which, when final, will, as appropriate, revise or supplement the 2009 Guidance to Industry on Patient-Reported Outcome Measures|
The FDA previously held a number of patient-focused drug development meetings, each focusing on a different disease area. Through these meetings, the agency found that patients often are experts on the day-to-day effects of their disease, and “what patients care most about may not always be factored into clinical trials or approved labeling.” As a result, the recently issued draft guidance is intended to provide drug developers with the FDA’s current thinking on steps they can begin taking to incorporate patient perspectives early in the drug development process and recommendations for discussing those plans with the FDA to ensure the usability of those data.
The draft guidance, titled “Patient-Focused Drug Development: Collecting Comprehensive and Representative Input,” focuses on how to effectively define the patient population for collecting information and methods for collecting patient experience information, and contains a number of recommendations for industry. In this client alert, we provide an overview of the draft guidance and its recommendations along with a snapshot of the commercial opportunity beyond informing drug development that patient experience data can serve. Lastly, we discuss the FDA’s upcoming two-day public workshop on October 15-16, 2018, during which the agency will gather feedback from stakeholders to help develop its next draft guidance on patient-focused drug development.
Background on Patient Experience Data
Patient experience data can be useful for designing clinical trials and selecting endpoints, and it can be used in submissions for regulatory review, including product labeling. In the draft guidance, the FDA defines patient experience data as “data intended to provide information about patients’ experiences with a disease or condition, including the impact (including physical and psychosocial impacts) of a disease or condition, or a related therapy or clinical investigation on patients’ lives; and patient preferences with respect to treatment of their disease or condition.” The draft guidance further explains that patient experience data includes patient perspectives and priorities related to the history of their condition and the impact of symptoms and treatments on their quality of life, as well as feelings and preferences that patients have related to the treatment of their disease.
This description aligns with Section 3001 of the 21st Century Cures Act, which amended Section 569C of the Federal Food, Drug, and Cosmetic Act to define patient experience data as data that “(1) are collected by any persons (including patients, family members and caregivers of patients, patient advocacy organizations, disease research foundations, researchers, and drug manufacturers); and (2) are intended to provide information about patients’ experiences with a disease or condition, including—(A) the impact of such disease or condition, or a related therapy, on patients’ lives; and (B) patient preferences with respect to treatment of such disease or condition.”
The FDA’s key recommendations to industry in its recent draft guidance include:
Choosing a Patient Population
- Consider the relationship between the research goals and methods of the proposed study when choosing a patient population from which to collect information.
- Patients should report their experiences and preferences directly whenever possible.
- Where necessary, data collected from patients may be supplemented with input from clinicians and other subject matter experts.
- Have early discussions with the agency regarding how information about the patient population could inform medical product development and regulatory decisions in the future.
- Research plans should seek to produce data that are not only representative of the target population, but also objective, relevant, and accurate.
- Such a plan should consider socioeconomic, demographic, and cultural factors, as well as literacy and clinical characteristics of the intended patient population.
Study Design for Collecting Patient Experience Data
- Consider the goals of collecting patient experience data, the target population and the availability of members of the target population, and what information is most relevant to answering the research questions, as well as budget and timing.
- Be specific when defining research objectives and consulting previous research studies, literature in the field, and subject matter experts.
- Collecting information from patients from a single site is discouraged; instead, studies should include patients from a diverse set of sites.
- Adjust research objectives, as necessary, if sample size is limited due to practical limitations (e.g., the disease being studied is rare), and communicate this limitation in the data report.
- Choose a method that will actively engage patients in the development process.
- All researchers involved should receive standardized training and have defined roles outlined in the protocol to reduce potential site issues.
Recommended Sampling Methods
- Consider research objectives when choosing a sampling scheme and consult with subject matter experts wherever possible.
- Ensure that the sampling method will produce data that are representative of the target population; an appropriate sampling method is one that allows research questions to be answered within the constraints of the research study.
- Such a method should include a well-defined target population, a clear list of the individual participants, and a mechanism for randomly selecting a sample.
- Specific sampling methods include observations, interviews, questionnaires, and audiovisual and digital approaches.
- With respect to questionnaires, all participants should be asked the same, pre-tested questions that address only one concept at a time and provided with distinct response options to facilitate understanding and avoid confusion.
- If using audiovisual materials, obtain permission for use of materials and web content as well as informed consent.
- Try using social media tools to collect information, but be mindful that certain tools are more appropriate for particular demographic groups, and that data collected in this way should adhere to standards to avoid potential limitations and ensure integrity of the data.
- If using Digital Health Technology, discuss the proposed method early with the FDA to obtain feedback from the relevant division.
Analysis of Patient Experience Data
- Once the patient experience data have been collected, align approaches for compiling, organizing, classifying, and interpreting the data with the research goals outlined in the protocol.
- Anticipate that there may be missing data and plan accordingly by establishing strategies in the study design to minimize and understand missing data.
- Provide a table summarizing missing data and establish steps in the protocol for handling missing data in the analysis.
- Collaborate with others, such as clinicians and subject matter experts, and consult available registries and databases to utilize existing data where primary data may not be feasible, with the caveat that care should be taken to ensure the integrity of the data and the methods by which they were collected.
- Establish a data management plan early in the study design process to standardize data collection and storage and provide a record of the planned research study.
- Comply with appropriate data and regulatory standards even if the study is not conducted to support a regulatory medical product application or medical product labeling language because any clinical data eventually intended for submission will be subject to such standards.
Submission of Patient Experience Data to the FDA
- When submitting patient experience data to the FDA, include a report and protocol from the research study, including information about data collection.
- Discuss specific data collection criteria with the agency early in the study design process and explain the rationale for submitting patient experience data to obtain feedback related to the study protocol from the relevant division.
- There are many existing FDA regulations and guidances that govern the collection and submission of clinical data, and those and other regulations (such as product labeling requirements) may apply to the submission of patient experience data.
- Comply with all applicable laws and policies related to the use of patient information, informed consent, and IRB requirements, and conduct studies according to good clinical practice.
- Additional information is forthcoming regarding the procedures for submitting patient experience data to the FDA.
A Commercial Benefit: Patient Experience Data in Drug Labeling
Patient experience data supporting a new drug or biologic approval can be especially important in the commercial stage, as drug manufacturers prepare marketing and advertising campaigns both for healthcare professionals and patients alike. In particular, having patient experience data included in FDA-approved drug labeling provides an FDA-approved means for talking directly to healthcare professionals and patients about data points and outcomes meaningful to them. Moreover, it gives the drug manufacturer or marketer the ability to promote approved drug products using the patient’s voice, which can be very impactful and resonate well with both physician and patient audiences.
A drug approval the FDA issued last summer highlights how patient experience data can be incorporated into product labeling and promotion. In June 2017, the FDA approved Rituxan Hycela™ (rituximab/hyaluronidase human), a subcutaneously administered product indicated for the treatment of several oncologic conditions. The FDA had previously approved Rituxan® (rituximab), an intravenous product, for the same oncologic indications (as well as additional indications). The subcutaneous product is infused over 5-7 minutes, whereas the intravenous product is infused slowly, over 1.5-4+ hours.
In a dedicated, open-label study conducted to support the development and approval of Rituxan Hycela, patients were assigned to receive either intravenous Rituxan or subcutaneous Rituxan Hycela (after one cycle of the intravenous product). After four cycles, the patients were crossed over to the alternative route of administration and asked to complete a questionnaire about their patient experience. Specifically, a Patient Preference Questionnaire asked three questions: (1) which route of administration the patient preferred; (2) how strong the preference was; and (3) the two main reasons for that preference. The sponsor submitted these data to the FDA for review and inclusion in its product labeling. As a result, Rituxan Hycela’s approved labeling includes a dedicated “Patient Experience” section that includes the sponsor’s patient preference findings, namely that 77% of patients studied preferred the subcutaneous dose, as well as the reasons patients provided for preferring the subcutaneous or intravenous administration. The manufacturer then leveraged these data commercially, promoting that “Nearly 8 in 10 Patients Preferred” Rituxan Hycela to Rituxan administration—a claim that may have significant importance in a cancer patient population focused on quality of life concerns—and the patient experience data paved the way.
Sponsors should not overlook the FDA’s willingness to include a dedicated “Patient Experience” section in approved product labeling, especially when developing research plans for new products in crowded treatment spaces or ones not well-understood by professionals or patients. We expect that designing patient experience studies with commercial utility, as with the example above, will become a routine part of drug development over time.
The Road Ahead
On August 13, 2018, the FDA announced an upcoming two-day public workshop on the next phase of its patient-focused drug development initiative. The workshop will be held October 15-16, 2018 and will focus on:
- methodological approaches to identifying what is important to patients with respect to disease burden and disease management; and
- developing clinical outcome assessments to measure patient experience in clinical trials.
The FDA is seeking feedback, in particular, on (1) methods to identify what is important to patients; (2) best practices for eliciting information on which aspects of disease symptoms, signs, impacts, and other issues are important and meaningful to patients; (3) measuring symptoms, signs, impacts and other issues of a disease or condition in a meaningful way; and (4) selecting, developing, or modifying fit-for-purpose clinical outcome assessments to measure patient experience in clinical trials. The FDA will use the feedback from this workshop in developing its next draft guidance on this topic.
Patient-focused drug development carries important benefits for both patients and developers. For developers looking to design patient experience studies and develop commercial plans for leveraging those data, working closely with the FDA at the outset to ensure agency buy-in on the planned study design and methodology will be important, as with any clinical trial. Conducting such a study that yields a post-approval commercial marketing benefit may be even better, as seen with Rituxan Hycela, so working earlier than usual in drug development with a marketing team may prove worthwhile to understand the commercial opportunity and competitive space.
Special thanks to Amanda White, a Goodwin 2018 summer associate, for assisting with the preparation of this alert.
 21st Century Cures Act, Pub. L. No. 114-255, 130 Stat. 1034 (2016).
 See FDA Plan for Issuance of Section 3002 Guidance (June 9, 2017), available at https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM563618.pdf.
 The FDA is required to work toward the goal of publishing a revised draft or final guidance within 18 months after the close of the public comment period on the draft guidance. See PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2018 Through 2022, 28-29, available at https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm511438.pdf.
 See Patient-Focused Drug Development: Disease Area Meetings Held in Fiscal Years 2013-2017, available at https://www.fda.gov/forindustry/userfees/prescriptiondruguserfee/ucm347317.htm. Patient-focused drug development (PFDD) meetings were conducted by the FDA as part of the agency’s commitments under PDUFA V, but were not included as part of PDUFA VI. Now, patient organizations have begun hosting their own externally-led PFDD meetings.
 Draft Guidance at 2.
 Id. at 9.
 Id. at 5.
 21 U.S.C. § 360bbb–8c.
 See Patient-Focused Drug Development: Collecting Comprehensive and Representative Input; Draft Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders (June 2018) (herein “draft guidance”), available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM610442.pdf.
 83 Fed. Reg. 40,057 (Aug. 13, 2018).
 Id. at 40,058.