By Deborah Borfitz

July 14, 2021 | Ensuring patient engagement methodologies are “fit for purpose” from the beginning was the topic of conversation among experts from Europe and the U.S. during the recent DIA 2021 Global Annual Meeting. The manner of engagement directly influences the quality of data collected, according to panel moderator Nathalie Bere, who is responsible for patient and consumer engagement at the European Medicines Agency (EMA). 

The importance of patients’ voice, as well as the diverse experiences and opinions of caregivers is “at the heart” of everything done at the U.S. Food and Drug Administration (FDA), says Andrea Furia-Helms, director of the office of patient affairs. “The evolution of patient engagement at the FDA has been going on for over 30 years” and the pivotal event was the HIV crisis of the late 1980s.

Initially, the patient affairs function was heavily focused on oncology but grew to encompass other serious, life-threatening conditions, she says. Office-specific roles gave way to broader programs and activities, public-private partnerships, and enhanced external communications. 

Important components of patient affairs today include Patient Listening Sessions, Patient Engagement Clusters, and the Patient Engagement Collaborative, Furia-Helms continues. The listening sessions are focused primarily on rare diseases and serve to inform regulatory decision-making and educate review staff. 

During the sessions, patients discuss treatment burdens and priorities to consider when new medical products are being developed, she says. Patients and their advocates also learn more about how the FDA works, and the agency can in return listen and ask questions. 

Either party can request a listening session, notes Furia-Helms. Based on feedback from participants, the approach has been well-received by patients and advocates as well as FDA review staff. 

The FDA has collaborated over the years with the EMA on the development of Patient Engagement Clusters, including ones specific to pediatrics, oncology, hematology, pharmacovigilance, rare diseases, and blood products, she says. Topics of mutual interest are discussed during these quarterly meetings, and Health Canada recently joined the conversation. 

The Patient Engagement Collaborative is a partnership with the Clinical Trials Transformation Initiative that explores topics informing medical products development and regulatory discussions, Furia-Helms says. It is responsible for improvements being made to the agency’s website for patients and is modeled after the EMA’s Patients’ and Consumers’ Working Party (PCWP). 

One of many other patient engagement initiatives of the agency is the FDA Patient Representative Program, a cross-center initiative that allows patients and advocates to gain temporary government employee status and provide direct input to agency staff based on various qualifying criteria (e.g., personal experience with a disease), Furia-Helms says. Over 300 diseases and conditions are represented. 

“It’s not easy to know how to talk with the FDA,” she concludes. “So, we created a web form for patients and advocates called Patients Ask FDA.”

Broad Engagement

Since the EMA’s creation in 1995, patients have “continuously [been] at the center of all we do,” echoes Bruno Sepodes, PharmD, vice chair of the agency’s Committee of Human Medicinal Products (CHMP) and professor of pharmacology and pharmacotherapy at the University of Lisbon (Portugal). “But we like to hear from a bigger group of patients” representing the collective voice of many, he adds. 

A “landmark moment” was in 2000 when the first group of patients became full voting members on an orphan medicines committee, Sepodes says. The framework for interactions was the PCWP, created in 2006.

In 2014, a public engagement department was established as a platform for communication between scientists and patients, he continues. Last year, its utility broadened to crisis management.

Patients have increasingly been involved in EMA activities as representatives of their advocacy organization, but “work as individual experts” in rendering scientific advice and protocol assistance, on ad hoc expert groups, and in the review of documents. Engagement occurs along the lifecycle of medicinal products from pre-submission (e.g., orphan designation and pediatric plans) to the evaluation phase and post-authorization (e.g., Pharmacovigilance Risk Assessment Committee, or PRAC, making recommendations to the CHMP). 

“No one size fits all in terms of interacting with patients and committees,” says Sepodes. The type of interaction required—face-to-face dialogue, survey or patient preference questionnaire, one-on-one support, information sheets, videos, webpage, or annual training day—is situational. Flexibility is required on both sides.

Patients’ involvement in regulatory activities has been a “step-by-step progression,” broadening to include their membership on the EMA’s Management Board, Pediatric Committee, Committee for Advanced Therapies, and PRAC. They are also now routinely engaged in meetings of various Scientific Advisory Groups, he says, as well as CHMP’s oral explanation process aiding in the planning of submission strategies for marketing authorizations. 

In a newly initiated pilot, patients are being engaged in early dialogue about a rare disease product rather than at specific points in the product lifecycle, Sepodes reports. The expectation is patients will be better prepared for conversations that happen later. 

As an example of how patients have previously been engaged, he points to their recent role in the Committee for Orphan Medicinal Products. Twenty-four patients, as well as 49 healthcare providers, responded with feedback on the benefits of the anti-cancer medication bortezomib. 

Via Survey Monkey, the agency also received input from 274 patients in one week on drugs they were using at home to treat Dravet syndrome. The data was used in an article published in 2015 (DOI: 10.1016/j.yebeh.2014.12.028) and was helpful in the design of clinical trials for fenfluramine, which received EMA market authorization last year for treating the rare type of epilepsy, says Sepodes.  

Patients are successfully engaged when they are treated as valued members of the team, he says, and their input has been especially critical over the last year in discussions about vaccines and how to channel public health messages.

Looking ahead, Sepodes says patients will be engaged in conversations about health technology assessment methodologies and contribute to multi-stakeholder projects of the Innovative Medicines Initiative. The EMA also plans to expand its patient engagement capacity and network outreach and enrich training and support with new tools and content.

Patient Perspectives 

A patient’s perspective on EMA engagement efforts comes from Marco Greco, president of the European Patients’ Forum, an independent umbrella organization founded in 2003 that represents 77 national coalitions and disease-specific organizations in the EU. He has personal experience as a patient expert and member of PRAC and the EMA’s Management Board as well as “a stakeholder asking for specific activities to be performed by the EMA.”   

Patients variably work with the EMA as a single patient expert or as a representative of a patient group or patients more universally, he says. Progress has been marked by a movement from patient engagement to early patient engagement and programs designed for patients to those co-designed with them. 

With PRAC, the “big question” initially was whether it was possible for patients to play a more active role in the risk assessment process in pharmacovigilance, says Greco. After nine years, results have shown their value is immense. 

Greco has participated in two PRAC public hearings, the first in 2017 around how to minimize harm from the epilepsy treatment valproate to unborn babies and the second in 2018 to raise awareness on the extent of side effects from two classes of broad-spectrum antibiotics (quinolones and fluoroquinolones).

Learnings from the second hearing were that important symptoms are wide-ranging and life-changing and that patients were not getting enough information about the risks, he shares. Healthcare professionals were also unaware of the range and severity of possible side effects from the two antibiotics.

Key proposals emerging from the hearing were to restrict use of the antibiotics, improve educational efforts and communication about the side effects, and encourage further research and better management of undesirable effects of taking the drugs, Greco says. 

While patients interact with the EMA through the PCWP framework, healthcare providers do so through a parallel platform called the Healthcare Professionals' Working Party, he notes. The two groups will often jointly meet.

His experience on the EMA’s Management Board has been completely different, Greco continues, in that it comes with voting rights and allows him to see the regulatory process close up. 

The EMA responded to requests by patient communities to broadcast a trio of live events during the pandemic so European citizens could have a “direct dialogue” with the agency, Greco adds. The first one last December focused on the EU regulatory processes for the approval of COVID-19 vaccines and the agency’s role in their development, evaluation, approval, and safety monitoring. Two similar public stakeholder meetings were subsequently broadcast in January and March to keep citizens up to date on vaccine development and the expected impact at the community level. 

What has made all this possible? According to Greco, a willingness to do it, training program, patient engagement team at the EMA, and a secretariat providing technical, scientific, and administrative support. Patients’ organizations are also providing training and capacity-building programs, notably the  Summer Training Course for Young Patient Advocates (STYPA). 

Improvement opportunities include investing in training of “expert patients,” economic support to patients so they can financially afford to get involved, helping patients with the workload created by bureaucratic barriers, and using the previous experiences of other patients, Greco concludes.