Executing Patient-Focused Drug Development (PFDD)

Veristat’s Science Advisory Board met on 14 March 2023 to discuss Executing Patient-Focused Drug Development (PFDD), with a focus on the application in rare diseases.

Patient health and wellness extend beyond biology and symptoms of disease, encompassing functional status (day-to-day experience), access to care, health perceptions, and quality of life. Depending on the severity and outcome of disease, there may be certain benefit-risk tradeoffs between improving the biological and physiological impact of disease and enhancing the patient’s daily function and quality of life. For instance, chemotherapies extend cancer patients’ lives but come with significant adverse effects that impact the patient but may be acceptable in the setting of a life-threatening disease. In other settings, patients may be less tolerant of such adverse effects, making certain treatments less viable options, despite their potential impact on disease biology.

As the drug development industry continues to shift towards a patient-centric approach, real-world data is crucial for informing medical product development and regulatory decision-making. To develop a patient-focused strategy, researchers must gain a deep understanding of various aspects of the patient experience, including their primary concerns and the burden of disease and existing treatments. These factors vary substantially among individuals and diseases and therefore should be considered separately for each indication examined.

Understanding and Collecting Patient Experience Data

Patient experience data can be defined as information collected from any persons (including patients, family members and caregivers of patients, patient advocacy organizations, etc.) that are intended to provide information about patients’ experiences with a disease or condition, including the perspectives, needs, and priorities of patients including but not limited to (Cures Act, 2016):

• Biological and physiological impact of disease and its natural history
• Impact of the conditions on patients’ function and quality of life
• Relative importance of issues defined by patients
• Patient preferences for outcomes with respect to the treatment of disease or condition

Patient experience data may include:

• Registry Data – Collection of data that tracks and monitors patients’ characteristics, treatments, and outcomes, providing insights into real-world patient experiences, treatment patterns, and population-level outcomes.
• Natural History Study Data – Observational or non-interventional study that aims to understand the progression and characteristics of a disease or condition over time.
• Patient Focus Groups or Meeting Reports – Qualitative insights and quantitative data capturing experiences, preferences, and perspectives from focused group discussions with patients, caregivers, family members, and patient advocacy organizations.
• Patient Survey Data – Information captured directly from patients in various formats, including virtual or in-person interviews.

Impact of Patients, Caregivers, and Patient Advocates on New Research

When patients, caregivers, and/or patient advocates are actively engaged in the development process or program planning, sponsors can better inform clinical trial design, trial endpoint development and selection, and regulatory reviews, including benefit-risk assessments.

Early and active involvement of patients and patient organizations can direct research, thereby allowing sponsors to target products that have potential therapeutic effects across the specific functional or symptomatic aspects that are most meaningful to patients. Sponsors can use this information to determine which measurement tools are most suitable for assessing disease progression among these critical items, as well as how frequently the measurement scales will need to be re-assessed in relation to the expected day-to-day variability and the rate at which disease progression occurs.

Role of Patient Input in Regulatory Decisions with Agencies

The patient experience also plays a crucial role in influencing regulatory agencies and shaping the assessment of risks and benefits for novel treatments. FDA and EMA use scientific expertise to evaluate the benefits of a novel drug and determine the level of uncertainty surrounding those benefits. The same process occurs with risks.

The balance between risk and benefit is subjective and must consider patients’ perspectives and willingness to tolerate the associated risks of the novel therapy. Patients suffering from rare and/or devastating diseases that drastically impact their daily function, have shortened life expectancy, or accelerated disease progression may be more inclined to accept a higher level of risk for the opportunity to alter the course of disease.

Patient organizations can educate the FDA directly through two meeting opportunities:

1. Public patient-focused drug development (PFDD) meetings, formatted to engage patients on the most significant symptoms of their disease, the impact of the disease on their daily lives, as well as views on available treatment.
   
   
2. Listening sessions, formatted as small, informal meetings between patients, caregivers, advocates, and FDA staff to discuss patient experience, perspective, and needs related to health or disease.

To ensure that the needs and concerns of patients and consumers are represented, the EMA directly engages with a network of more than thirty-five eligible patients and consumers organizations.

Key Advantages of Patient-Focused Drug Development (PFDD)

As the FDA becomes more educated on the patient experience through PFDD meetings and listening sessions, it is critical for sponsors to also connect with patients, caregivers, and advocates so that the planned endpoints to establish and confirm an effective treatment remain relevant and impactful for patients and the course of their disease. PFDD is an important approach for validating endpoints and ensuring that they are:

• Fit-for-purpose in measuring and assessing important aspects of disease progression or functional impact for patients.
• Reliable with consistent and repeatable measurement across assessors.
• Can measure change within patients over time or between patients.

Other advantages of PFDD include:

• Patients and families know they are heard which can help patients to stay engaged and on board with the research and clinical development program.
• It provides evidence to regulatory agencies that the quality of the improvement made by a novel treatment is meaningful and impactful.
• Patient-focus and patient-input can help identify endpoints for research and more widely direct protocol development, including inclusion/exclusion criteria, plans for follow-up, and the study procedures to be implemented; can also reduce needs for protocol amendments, increase enrollment, and increase regulatory acceptability.
• Relationships with patient organizations can be critical to advancing knowledge and understanding of the disease at regulatory agencies through use of educational PFDD meetings and listening sessions.
• Alignment of treatment impact between patients, researchers, and regulatory agencies

Leveraging PFDD for Successful Clinical Development

The ultimate success of a clinical development program lies in answering the fundamental question of whether a drug is safe and effective in positively impacting the patient’s disease, functional capability, and quality of life. Prioritizing patient experience early on and throughout the clinical development program can improve the chances of a successful study in terms of statistical and clinical significance as well as the impact on patients.

If the goal is to take a patient-focused approach, Veristat experts recommend involving the patient experience within your study and program planning, starting with smaller discussions, focus groups, or interviews with patients, caregivers, or advocates.

Learn more 

• Strategic Regulatory Consulting & Planning
• Decentralized Solutions for Patient Enablement
• Natural History Trials for Rare Diseases
• Full-Service Clinical Development Solutions