Integration of Patient-Reported Outcomes (PROs) and the Patient Voice: A Review of 6 Health Technology Assessment (HTA) Agencies

HTA QUARTERLY | SPRING 2020

Integration of Patient-Reported Outcomes (PROs) and the Patient Voice: A Review of 6 Health Technology Assessment (HTA) Agencies

By: Martine Etschmaier, MPH; Kimberly Gittings, PharmD, MS, MBA; Cynthiya Ruban, PhD, MS; George Papadopoulos, BSc(Hons); Trent McLaughlin, BSc(Pharm), PhD

In recent years, some health technology assessment (HTA) agencies have been utilizing patient-reported outcome (PRO) instruments and inclusion of the patient voice when evaluating pharmacotherapies or medical technologies. As patients are intended to be the first beneficiaries of health innovation, inclusion of patient views, experiences, and concepts of value in the key stages of the HTA process is vital.

While inclusion of PROs and/or patient voice within an HTA can have a positive influence on recommendations, inconsistencies in terms of how this information is collected across HTA agencies and across different assessments within the same HTA agency is problematic for manufacturers. For example, many HTAs may not directly reference the use of PROs within the evaluation but may indirectly utilize them through economic models. Different HTA agencies place heightened value on some specific outcomes more than others and provide guidance on how certain PROs should be utilized in drug development. The differing value of PROs and patient voice by country is strongly reflected by the respective processes of HTA agencies’ assessments.

This article provides a brief overview as to how the patient voice and/or PROs are utilized in HTA decision making within Australia, Canada, Germany, Sweden, the United Kingdom, and the United States.

- World Health Organization, 2019

“Health technology assessment (HTA) refers to the systematic evaluation of properties, effects, and/or impacts of health technology. It is a multidisciplinary process to evaluate the social, economic, organizational, and ethical issues of a health intervention or health technology. The main purpose of conducting an assessment is to inform policy decision making.”

Australia

The patient voice is integrated into the decision-making process via 3 specific mechanisms in the Pharmaceutical Benefits Advisory Committee (PBAC) submission process: 1) by obtaining consumer comments on submissions to the PBAC Meetings; 2) through PBAC Stakeholder Meetings; and 3) via the diverse PBAC membership that includes doctors, health professionals, health economists, and consumer representatives. PROs are mentioned within guidelines for manufacturers preparing submissions to the PBAC and are recommended to be included as details to inform clinical health outcomes in models for economic evaluation, though not mentioned as relevant efficacy endpoints. Details for the justification of use of the PRO measure must be included in the submission, and there should be a reliable existing method of transforming the PRO data into utility weights for the model.

Country Spotlight: Australia

As stated above, Australia allows the patient voice to be integrated into the decision-making process via 3 specific mechanisms in the PBAC submission process, first by obtaining consumer comments on submissions to the PBAC Meetings. The public is welcome to provide comments whether they are a patient, carer, member of the public, health professional, or member of a consumer interest group for consideration by the PBAC, alongside the information submitted by the sponsor when the submission is considered.

Secondly, the PBAC convenes Stakeholder Meetings from time to time as it finds itself in the position of being unable to recommend a drug for listing on the basis of cost-effectiveness, due to either an insufficient degree of clinical effectiveness and/or a high price. Stakeholders may include the drug’s sponsor or manufacturer, patient groups, medical specialists, and general practitioners with a particular recognized interest in the drug, as well as the Department of Health. The aim of these meetings is to inform stakeholders of the situation, seek their views, and, if possible, define a listing restriction acceptable to the parties that will give the best possible cost-effectiveness, even if at a level that would normally be unacceptable (the “Rule of Rescue”). The meetings are not intended as an appeals mechanism but rather as a “without prejudice,” non-adversarial process in order to facilitate a re-submission to PBAC by the sponsor or manufacturer.

Stakeholder Meetings may be initiated by the PBAC or the sponsor on occasions when the PBAC Chair, in consultation with other PBAC members as appropriate, is satisfied that each of the following has been met:

The drug is indicated for a serious, disabling, or life-threatening condition for which there is no other realistic management option. This could include drugs that are indicated where other management options have failed for such conditions (last resort); and
All reasonable normal options, which may include a re-submission, have been exhausted; and
The PBAC considers there are grounds to define a listing restriction that would be accepted by the stakeholders and would give the best possible (if still normally unacceptable) cost-effectiveness under the “Rule of Rescue”; and
The PBAC and the sponsor agree there is a reasonable likelihood that progress will be able to be made that will assist the PBAC in reaching a recommendation.

A record of the Stakeholder Meetings is made available online, and, since 2014, 11 Stakeholder Meetings have been recorded for various products.

Lastly, the PBAC membership includes doctors, health professionals, health economists, and consumer representatives. The current Deputy Chair of the PBAC is also the Chair of the Health Technology Assessment Consumer Consultative Committee, Deputy Chair of the Consumers Health Forum, and a long-standing consumer nominee and advocate, while the second consumer nominee has been heavily involved with consumer representation focused on people with chronic illnesses.

Canada

In 2010, the Canadian Agency for Drugs and Technologies in Health (CADTH) created opportunities for patient groups to contribute to HTAs in the Common Drug Review (CDR) process. CADTH chose to include patients, as they have unique knowledge about the disease and treatment that can and should inform an HTA. Additionally, patients play an essential role, as they are able to identify potential benefits and harms that are important to them and knowledgeably comment upon whether the benefits outweigh the harms when assessing treatments. A study of 30 consecutive assessments explored whether, and how, patient insights were integrated into assessment reports and recommendations by the CADTH Canadian Drug Expert Committee (CDEC). Findings from this study reported that, between 2010 and 2015, 114 patient groups provided 297 patient input submissions to CDR, contributing to 142 reimbursement recommendations. While limited PROs are incorporated into the CADTH reports and recommendations, integration of the patient voice allows valuable insights on the impact of treatments, ensuring that clinical trial data are interpreted for relevance to patients within the Canadian healthcare setting.

Germany

Germany’s Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) has been noted as one of the few HTA agencies that specifically assesses PROs. However, the use of PROs in the assessment is not required, and the specific PRO selected depends on the evaluation method (or trial design) and should be direct measures of health outcomes, not necessarily a process measure such as treatment adherence or satisfaction. PROs measured in blinded randomized clinical trials are seen as most informative due to the subjective nature of PROs, and, therefore, PROs measured in non-blinded studies are considered by IQWiG to have limited validity. Both IQWiG and the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA, the organization that determines reimbursement for pharmaceutical products) in Germany use PROs when available in estimating effectiveness or safety in their assessments.

Sweden

Both Sweden’s Council on Technology Assessment in Health Care (Statens beredning för medicinsk utvärdering, SBU) and the Swedish Dental and Pharmaceutical Benefits Agency (Tandvårds-och läkemedelsförmånsverket, TLV) conduct HTAs and have used PROs in their assessments of effectiveness or safety. While these agencies see PROs as influential to the understanding of the benefit from the patient perspective, they are not always used in the appraisal of evidence. Given the SBU and TLV emphasis on unmet needs and human dignity for the prioritization of resources, there is precedence for using quality of life, patient willingness to pay, and other trade-off studies as supporting evidence for reimbursement decisions.

United Kingdom

PROs are not mentioned or described in respect to how they are utilized or considered, if at all, within the National Institute for Health and Care Excellence (NICE)’s Guide to the Processes of Technology Appraisal. Interestingly, NICE has produced several guidances specific to certain disease states (eg, colorectal cancer, musculoskeletal conditions), which highlights the importance of the development of PRO measures for use in disease management and clinical trials. Recent NICE appraisals do not suggest that PRO data are utilized directly within the assessment of efficacy; rather, NICE may utilize PRO data as a surrogate endpoint for other parts of its evaluations (ie, within a cost-effectiveness calculation).

United States

The Institute for Clinical and Economic Review (ICER) is an independent and non-partisan research organization that conducts value assessments of select therapeutic areas and products and invites key stakeholders—including patients and patient advocacy groups—to participate at various points during its value evaluation process (eg, public comment periods and a public meeting). While there is limited inclusion of the use of PROs within ICER’s comparative efficacy or economic evaluations, there is substantial opportunity for the patient voice and experience to be considered throughout ICER’s review process. In an assessment of 4 of ICER’s final value assessment reports (non-small cell lung cancer, osteoporosis, ovarian cancer, and migraine), the extent to which ICER has acknowledged and incorporated input from patients was assessed. Findings from this report indicate that patient advocates were the driving force behind comments on the patient perspective; however, comments from patient advocates were least likely to be acknowledged and incorporated (15.9%). While there is still limited integration of the patient perspective within ICER’s assessments, ICER can improve its engagement with patients by optimizing its public comment period.

Therapeutic Area Spotlight: Oncology

PROs have been used in a number of therapeutic areas such as immunology, pain, respiratory, etc, for decades to capture health outcomes important to patients within the clinical trial setting. With the expanding role of the patient voice in the drug development process, there has been an increase in inclusion of PRO data in HTA submissions across multiple disease areas, most notably oncology. The use of PROs in oncology has been on the rise more recently with the pressure to demonstrate benefits of new therapies beyond survival/life extension, particularly when overall survival data are not mature at the time of regulatory submission. PROs, including both general and disease-specific instruments, are increasingly used as endpoints in oncologic clinical trials and taken into account in the value assessments. The use of PROs is not only increasing but also becoming more influential, with a number of recent positive recommendations being driven by PRO data despite limited survival data.

Conclusion

The increasing inclusion of patients’ perspectives and experiences as an influential part of the HTA process makes it essential for manufacturers to include the patient perspective early within the drug development process and throughout life-cycle management, as it represents an invaluable and distinctive source of data. The extent to which patients are involved in HTAs and the relative influence varies. Moreover, patient perspectives are captured without systematic or agreed methodologies. This means that, while patient input is considered, the current assessment methodology does not always capture how treatments are valued by patients, as patient experience can be particularly hard to quantify compared against other evidence such as clinical trial data. Globally, to enable patients to contribute to decision making in HTA, it is vital to design and employ appropriate research methods to elicit, collect, and adequately value patient preferences and views. Given the diversity of patient voice and PRO integration in the HTA process, it is important that manufacturers seek local feedback to remain knowledgeable of changes that may impact a product’s submission.

The influence and the role of the patient voice in healthcare decision making are on the rise. While the exact level of utilization varies widely from HTA agency to agency, the trend seen across global markets is clear. As such, as manufacturers continue to develop their pipeline products, strategic and timely integration of the patient voice and PROs into clinical development programs will be critical to ensure the data are available for inclusion in both regulatory and HTA submissions. Manufacturers will be challenged to not only identify and utilize appropriate PRO instruments to capture the patient experience of the specific patient population but also develop appropriate methodologies for capturing these data within both clinical trial and real-world settings. It is essential that manufacturers integrate the patient voice, an invaluable and distinctive source of data, throughout the drug development cycle as it will drive value and bring new, innovative therapies to market—which is a winning value proposition for all stakeholders.

Summary of HTA Agencies

The article should be referenced as follows:

Etschmaier M, Gittings K, Ruban C, Papadopoulos G, McLaughlin T. Integration of patient-reported outcomes (PROs) and the patient voice: a review of 6 health technology assessment (HTA) agencies. HTA Quarterly. Spring 2020. https://www.xcenda.com/insights/htaq-spring-2020-pro-patient-voice-hta.

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