Can Patients Help Influence Drug Development? Where are We with Respect to Patient Input on Early Scientific Advice in North America and Europe?

By Xcenda |

Where are we with respect to patient input on early scientific advice in North America and Europe? Patient input is now actively being sought from many stakeholders and, in countries where universal health care predominates, patient input may even be mandated. We examine the current status of patient input into early scientific advice and the ensuing opportunities for the pharmaceutical industry.

HTA QUARTERLY | SPRING 2019

Market Trends and Updates: Can patients help influence drug development? Where are we with respect to patient input on early scientific advice in North America and Europe?

By David Campbell, PharmD, MS and Jo Watts-James, BSc, MBA
Regulatory agencies, including the Food and Drug Administration (FDA) and European Medicines Agency (EMA), and many health technology assessment (HTA) groups offer scientific advice, for a fee, to pharmaceutical manufacturers to elicit input on their clinical and economic evidence generation plans during the drug development process. Patient input is now actively being sought from many stakeholders and, in countries where universal health care predominates, patient input may even be mandated; for example, the National Institute for Health and Care Excellence (NICE) is required by the UK government to demonstrate that it has consulted with patient groups, and the EMA is legislated to implement specific forms of interaction with patients.
 
This article reviews the current status of patient input into early scientific advice and the ensuing opportunities for the pharmaceutical industry.
 

US and ICER

The FDA provides opportunities for manufacturers to engage the agency for formal consultation on various aspects of their clinical development programs. Under the Prescription Drug User Fee Act (PDUFA) VI, the FDA provides consultation through four types of meetings: Type A, Type B, Type B (end of phase [EOP]), and Type C for consultation of specific circumstances. Recent guidance and regulation has made clear that the FDA values the patient perspectives and manufacturers will be expected to present this type of data in these formal consultations. For example, FDA guidance on patient-reported outcomes (PRO) measures to support labeling claims recommends the use of a PRO instrument when measuring a concept best known by the patient or best measured from the patient perspective.

 

Meeting Type Meeting Criteria
Type A Type A meetings are used for stalled product development programs that require FDA approval to proceed or to address an important safety issue.
Type B Type B meetings can be used before key steps of the development program such as pre-investigational new drug application (pre-IND), pre-emergency use authorization meetings or pre-new drug application (pre-NDA)/pre-biologics license application (pre-BLA) meetings. Type B meetings can also be used for post-decision meetings, such as the issuance of a complete response letter, to discuss post-marketing requirements or discuss the overall development program for products granted breakthrough therapy designation status.
Type B EOP Certain end of phase (EOP) 1 study meetings are held for products that will be considered for marketing approval, and EOP 2 study or pre-phase 3 study meetings
Type C Discuss anything that does not fall under meeting Types A, B, or B EOP. In particular, this would include consultations for novel clinical outcome assessments.

 

Furthermore, the 21st Century Cures Act (Cures Act), which communicated FDA priorities, included greater patient involvement. The Cures Act provided increased funding for medical research and development (with a specific focus on oncology) and innovation, opioid addiction treatment and prevention, and mental health; and, developments in health information technology also made clear the FDA’s desire to increase the influence of patient and caregiver perspectives. Specifically, the Cures Act aims to increase patient and caregiver involvement and consideration of the patient experience, enhance the interoperability of electronic health records, and improve data management by increasing data-sharing and collaboration between stakeholders throughout the care continuum. 

In the US, the Institute for Clinical and Economic Review (ICER) has gained influence in its self-described role as the nation’s watchdog on drug pricing. The research organization aims to be an independent voice that objectively evaluates the clinical and economic value of prescription drugs, medical tests, and other health care and health care delivery innovations. ICER’s evaluations highlight the cost-effectiveness of technologies, as measured by the incremental cost per quality-adjusted life-year gained, and budget impact. However, the agency also seeks to incorporate the views of key stakeholders, including patients, doctors, life science companies, private insurers, and thengovernment into its evidence assessment and recommendations. ICER has specifically called out the importance of including the patient perspective in its assessments. The organization has stated its reports “become infinitely more comprehensive, actionable, and accurate” when patients are involved.

In November 2018, ICER announced it was considering offering life science companies early scientific advice as a fee for service operation. The service would establish a formal pathway for companies to receive ICER’s views and recommendations during their evidence generation plan development, so that modifications may be implemented. Manufacturers may benefit from this early guidance and utilize obtained insights to generate more useful clinical and HEOR data. If ICER decides to move forward with an early scientific advice offering, it will be a great opportunity for manufacturers to gain insights and communicate the unique value their agent offers patients. However, the proposed services have also generated concerns. Following the announcement, Bernstein biotech analyst Ronny Gal noted the fee for service as a potential means for manufacturers to gain influence over the organization that prides itself on independence. Few details of the potential service have been released, and it is unclear to what extent patient perspectives will be incorporated in the ICER early scientific advice process. However, given the organization’s previous patient advocacy efforts, it is likely that patient input will be a meaningful part of any process.

 

Canada and CADTH

In Canada, the Canadian Agency for Drugs and Technologies in Health (CADTH) Scientific Advice Program includes patient input as part of the process. In the briefing book submitted, applicants are asked to indicate any consultations or interactions they have had with patients or patient groups related to their drug development program. For each application, CADTH contacts at least one relevant patient group to arrange for a patient representative to speak with CADTH staff on current therapies and needs unmet by current therapies.

 

The European Experience

In Europe, the EMA offers early scientific advice to companies at any stage of development of a medicine and patients are invited to share their real-life perspective and experience in relation to a disease area. Patients may be asked to contribute by participating in meetings with EMA and the medicine developer or by providing written feedback on the proposed development plan. To maximize the value of patient insights, patients are sent information on the medicine to read before the meeting and a member of the EMA team contacts them to brief them on the information. During the meeting, patients answer questions and contribute at any time they feel it is appropriate. After the meeting, patients are sent the draft minutes for agreement.
NICE was the first HTA agency to establish an early scientific advice service followed by the Gemeinsamer Bundesausschuss in Germany and Agenzia Italiana del Farmaco in Italy. NICE actively encourages patient input; the NICE briefing book guidance has a section on patient engagement that asks companies to “describe if you have engaged with patients and/or patient organizations as part of your product development program, and the nature of that engagement.” 

Multiple agency advice is now available via European Network for Health Technology Assessment (EUnetHTA), a network of organizations that contribute to HTA in Europe. EUnetHTA offers early dialogue on pharmaceuticals either from HTA bodies only or in parallel between the EMA and HTA bodies. EUnetHTA is committed to involving patients/patient representatives in its work and is currently developing guidelines for patient input. Stakeholders such as European patient organizations are being consulted during this process. 

Regulatory and HTA bodies indicate that they value patient perspectives, but does patient input alter the advice given? A report on patient input shows that the number of patients involved in EMA scientific advice has risen steadily to 131 in 2017. The EMA indicated that in 27% of cases the advice to companies was modified as a result.

Figure 1. Involvement of patient representatives in scientific advice procedures at EMABar graph

 

Figure 2. The effect of patient input on EMA scientific adviceGraphic depiction of patient input

NICE recently announced that the NICE Scientific Advice team has provided its first piece of advice on the design of a patient preference study. Working with Novartis, the pilot looked at a patient preference study for people with chronic obstructive pulmonary disease (COPD), aimed at supporting the development of new products to treat patients with COPD. NICE anticipates that its advice will guide early evidence generation, helping to transform study design and improve the quality of current processes. 

Involving Patients Poses Some Challenges

At an ISPOR 2018 workshop, presenters from NICE, Health Technology Assessment international, and EuNetHTA discussed the challenges encountered in involving patients in early dialogues which included finding the right patient, understanding the patient consent process, and providing guidance on interviewing patients. National research associations such as the British Healthcare Business Intelligence Association and the Council of American Survey Research Organizations are ideally placed to facilitate patient input due to their established policies and manufacturers’ familiarity with these guidelines. However, and perhaps one of the key hurdles for manufacturers, the elicitation of patient input needs to be seen as independent of the manufacturer. For patient input to be credible, it must be seen as impartial; payers express concern that patient input may be biased if they are recruited via patient groups involved with manufacturers and that they are less likely to be influenced by what these patients have to say.

Finding the right patient is not just about finding a patient at the appropriate point in the treatment algorithm; HTA bodies and regulators are mindful of the problem of obtaining meaningful input from lay people that is to be reviewed by experts in the field. The EMA offers a training program including telephone briefing for patients and annual workshops for patient experts. A 2018 study interviewed 41 patient experts and committee members about their experience of providing and evaluating patient input into NICE technology appraisals. Comments from committee members indicated that patient input is highly variable; they are more interested in patients who can talk articulately about their disease and how it impacts their day-to-day lives than emotional, and arguably obvious, statements about the stress of living with a life-threatening condition such as an advanced cancer. For patients, tokenism was a recurring theme with some patients wondering why they were invited as their input was either not sought or they felt glossed over. This could be due to committee members undervaluing patient contributions or it could be due to patients having little to contribute; while patient input can be extremely meaningful, it may not be required in every situation.

To Summarize

Manufacturers should utilize early scientific advice programs to validate evidence generation plans and gain important insights into agency thinking. Over the years more regulatory agencies and HTA organizations are providing these services, and even the US cost watchdog ICER is considering offering them as well. Patient input into early dialogues is still developing but will be essential to align stakeholders on the relevant evidence and promote timely access. For manufacturers this means adapting their clinical development programs to facilitate patient input prior to phase 2 and 3 trials and educating their research teams on the need for this input to ensure it is both included and relevant. The reward for which is hopefully more meaningful evidence, improved treatments, and better access for patients.

 

 

The article should be referenced as follows: 

Campbell D, Watts-James J. Can patients help influence drug development? Where are we with respect to patient input on early scientific advice in North America and Europe? HTA Quarterly. Spring 2019. May 16, 2019.

 


 

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