Article
Unlocking the voice of patients: Are engagement initiatives truly transforming Canadian HTA reviews?
Patient engagement initiatives have emerged in droves over the last 25 years, both as standalone organizations and within regulatory and reimbursement agencies. Are these initiatives impacting the data submitted for reimbursement, and if so, how?
Traditionally, the evidence supporting drug treatment benefit primarily relied on clinical endpoints.
Since the early 1990s,1 the understanding of the importance of incorporating the ‘patient voice’ into the assessment of treatment efficacy has grown. Ultimately, the patient holds the best perspective of their experiences with a particular health state and treatment. While clinical outcome measures provide what are considered to be ‘hard’, unequivocal outcomes (eg, mortality, lab values, tumour shrinkage), they may not capture factors that impact the patient’s quality of life and those that matter most to the patient. Indeed, the patient experience may differ from treatment effects described by clinical outcomes; to the patient, negative side effects of treatment may outweigh apparent clinical benefits. Thus, the patient experience is critical to understanding and comparing the benefits and risks of treatment. When treatments have similar primary clinical outcome results (eg, similar survival), patient-reported outcomes (PROs) data can provide information about the impact of treatment on symptoms of the underlying disease, possible side effects, and how those experiences impact a patient’s daily activities.2
Results from PRO data may align with other clinical outcomes (eg, improvement in survival corresponding with improved symptoms), or they may provide contrasting results (eg, improvement in survival but decreased health-related quality of life [HRQoL]). Moreover, some diseases, such as rheumatoid arthritis (RA), lack objective patient-relevant clinical endpoints. Developing standardised PRO measures allows healthcare providers and researchers to assess patient symptoms, functioning, and HRQoL in a way that can be compared across groups of patients (eg, in clinical trials) or over time (eg, to assess patient response to treatment).3
Over the past 25 years, regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have become increasingly focused on taking the patient perspective into account when evaluating drug benefits. In 2000, the FDA developed a working group composed of members from the International Society for Quality of Life Research (ISOQOL), ISPOR (The Professional Society for Health Economics and Outcomes Research), the Pharmaceutical Manufacturer’s Association Health Outcomes Committee (PhRMAHOC), and the European Regulatory Issues on Quality of Life Assessment (ERIQA). They met to address the need to harmonise outcomes review criteria within and across U.S. and European regulatory agencies. Over time, the discussion expanded from HRQoL outcomes to include any outcome based on data provided by the patient or patient proxy—the working group, therefore, became known as the PRO Harmonization Group. In 2005, the EMA published ‘Reflection Paper on the Regulatory Guidance for the Use of HRQoL Measures in the Evaluation of Medicinal Products’, and in 2020 they held a cancer symposium titled ‘New Approaches in Patient-Focused Cancer Medicine Development’. In February 2024, the EMA and the European Organisation for Research and Treatment of Cancer (EORTC) jointly organised a workshop on how PROs as well as HRQoL data can inform regulatory decisions. Other recent developments in regulatory and professional societies’ PRO endeavours include the Institute for Clinical and Economic Review (ICER) announcing the creation of a Patient Council to advise on ICER’s patient engagement strategy, outreach, and process for input into drug reviews and broader initiatives in 2023. The Council comprises several patient representatives with a range of expertise on health technology assessment (HTA); the Council engages with ICER, offering a variety of perspectives for evaluation of the ICER process.
Similarly, HTA agencies have developed their own strategies for increasing patient engagement. For example, the National Institute for Health and Care Excellence (NICE) developed their Patient and Public Involvement Policy in 2013 so that their guidance ‘address[es] issues relevant to patients, service users, carers and the public, reflect[s] their views, and meet[s] their health and social care needs’.4 As part of this policy, NICE advisory committees include lay members (patients, services users, carers, or other members of the public) who work alongside clinical and methodological experts to ensure the guidance focuses on the needs of patients and their families. Although HTA reviews are conducted separately from regulatory reviews, both are typically based on the same registrational trials, amplifying the impact of decisions made during trial design. For the present endeavour, we sought to assess how Canada’s Drug Agency (CDA-AMC) has included the patient perspective into their health technology appraisals and how increasing emphasis on the patient experience has impacted the data available to inform this evaluation.
Over the past 25 years, regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have become increasingly focused on taking the patient perspective into account when evaluating drug benefits. In 2000, the FDA developed a working group composed of members from the International Society for Quality of Life Research (ISOQOL), ISPOR (The Professional Society for Health Economics and Outcomes Research), the Pharmaceutical Manufacturer’s Association Health Outcomes Committee (PhRMAHOC), and the European Regulatory Issues on Quality of Life Assessment (ERIQA). They met to address the need to harmonise outcomes review criteria within and across U.S. and European regulatory agencies. Over time, the discussion expanded from HRQoL outcomes to include any outcome based on data provided by the patient or patient proxy—the working group, therefore, became known as the PRO Harmonization Group. In 2005, the EMA published ‘Reflection Paper on the Regulatory Guidance for the Use of HRQoL Measures in the Evaluation of Medicinal Products’, and in 2020 they held a cancer symposium titled ‘New Approaches in Patient-Focused Cancer Medicine Development’. In February 2024, the EMA and the European Organisation for Research and Treatment of Cancer (EORTC) jointly organised a workshop on how PROs as well as HRQoL data can inform regulatory decisions. Other recent developments in regulatory and professional societies’ PRO endeavours include the Institute for Clinical and Economic Review (ICER) announcing the creation of a Patient Council to advise on ICER’s patient engagement strategy, outreach, and process for input into drug reviews and broader initiatives in 2023. The Council comprises several patient representatives with a range of expertise on health technology assessment (HTA); the Council engages with ICER, offering a variety of perspectives for evaluation of the ICER process.
Similarly, HTA agencies have developed their own strategies for increasing patient engagement. For example, the National Institute for Health and Care Excellence (NICE) developed their Patient and Public Involvement Policy in 2013 so that their guidance ‘address[es] issues relevant to patients, service users, carers and the public, reflect[s] their views, and meet[s] their health and social care needs’.4 As part of this policy, NICE advisory committees include lay members (patients, services users, carers, or other members of the public) who work alongside clinical and methodological experts to ensure the guidance focuses on the needs of patients and their families. Although HTA reviews are conducted separately from regulatory reviews, both are typically based on the same registrational trials, amplifying the impact of decisions made during trial design. For the present endeavour, we sought to assess how Canada’s Drug Agency (CDA-AMC) has included the patient perspective into their health technology appraisals and how increasing emphasis on the patient experience has impacted the data available to inform this evaluation.
How does CDA-AMC involve patients in the reimbursement process?
Under CDA-AMC, patient involvement in the reimbursement process has been relatively straightforward (Figure 1). Prior to conducting a review, CDA-AMC solicits input from patient groups, summarizes that input, and validates it with the patient groups. Following the review, patient feedback is requested on the recommendations. Patient input generally covers their experience with the disease and currently available treatments, unmet needs, and outcomes that are important to patients. In the methodology guidance for HTA reviews, CDA-AMC states that the outcomes of interest should include ‘clinically meaningful endpoints such as mortality; morbidity; and patient-reported experiences, symptoms, health behaviours, function, and health-related quality of life’.5 In April 2025, CDA-AMC announced they are undertaking a new initiative to identify ways to incorporate patient perspectives effectively while making the process more accessible for patient groups.6
Figure 1. CDA-AMC patient involvement
Key: CDA-AMC – Canada’s Drug Agency.
Figure 1. CDA-AMC patient involvement
Key: CDA-AMC – Canada’s Drug Agency.
Do reimbursement reviews include the data that really matter to patients?
In our evaluation of HTAs submitted to CDA-AMC, we focused on drug treatments for 3 conditions: non-small cell lung cancer (NSCLC), asthma, and RA. The 3 conditions were chosen as they exemplify the continuum of ways in which the subjective patient experience is incorporated into clinical outcomes. The main clinical outcomes used in assessing therapies for RA rely heavily on patients’ evaluations of their pain, ability to carry out daily activities, and global disease assessment. Clinical outcomes for asthma are more objective measures of lung function, but patient-reported symptoms are also commonly included. NSCLC clinical outcomes focus on objective measures of survival and response. Most trials included in the CDA-AMC reimbursement reviews on treatments for NSCLC (n=55 trials), asthma (n=37 trials), and RA (n=24 trials) reported at least some PRO data, although the types of PROs varied by condition (Figure 2).
Figure 2. Types of outcomes reported in trials in CDA-AMC reimbursement reviews
Key: CDA-AMC – Canada’s Drug Agency; HRQoL – health-related quality of life; NSCLC – non-small cell lung cancer; PRO – patient-reported outcome; RA – rheumatoid arthritis.
Figure 2. Types of outcomes reported in trials in CDA-AMC reimbursement reviews
Key: CDA-AMC – Canada’s Drug Agency; HRQoL – health-related quality of life; NSCLC – non-small cell lung cancer; PRO – patient-reported outcome; RA – rheumatoid arthritis.
The PROs captured in these trials have been categorised here as HRQoL, work productivity, composite outcomes (ie, outcomes that include some patient-reported information, such as pain; combined with clinician assessment, such as global disease assessment; and/or purely objective measures such as lab values), or other PROs (eg, specific disease symptoms, global assessments of disease, satisfaction with treatment). Across the indications, HRQoL was the most common type of PRO assessed; all RA trials also included at least one composite outcome (most commonly the American College of Rheumatology response criteria). Nearly all asthma and RA trials included at least one other PRO, typically assessing specific symptoms such as pain, fatigue, wheezing, or coughing. Additionally, patient-reported work productivity has been incorporated into some asthma and RA trials. Although the number of trials each year was small, the inclusion of HRQoL in asthma trials has increased over time (Figure 3). This aligns with reviews of data on ClinicalTrials.gov indicating that more recent trials are more likely to include PRO data.7,8
Figure 3. Asthma trials in CDA-AMC reimbursement reviews that included HRQoL measures by year
Key: CDA-AMC – Canada’s Drug Agency; HRQoL – health-related quality of life.
Figure 3. Asthma trials in CDA-AMC reimbursement reviews that included HRQoL measures by year
Key: CDA-AMC – Canada’s Drug Agency; HRQoL – health-related quality of life.
What should we target next?
The results of our exercise indicate that HRQoL was assessed in the majority of NSCLC, asthma, and RA trials included in CDA-AMC reviews. The specific PRO measures used across studies varied; some used generic HRQoL scales (eg, EQ-5D), while others used disease-specific scales. In the 30 asthma trials that assessed HRQoL, most used the Asthma Quality of Life Questionnaire (AQLQ); however, there was variation in the AQLQ version. When looking at the tools used to assess symptoms in asthma trials, the landscape is even more heterogeneous. Although there are methods to quantitatively compare different tools used to assess the same construct, these methods often reduce interpretability of the data.9 In addition, some of the methods (eg, using a threshold to convert continuous measures to dichotomous outcomes) can only be applied with individual patient data from the original trials, which are oftentimes inaccessible to many systematic reviewers and stakeholders. There have been efforts to develop core outcome sets for many disease areas (ie, a standardised set of outcomes that should be collected in all new trials).10-13 However, adoption of core outcome sets is still somewhat limited and depends heavily on the disease area.14 For some disease areas, there are dozens of published core outcome sets, resulting in the same problem on a different scale.
Much of the improvement in the collection of HRQoL and other PRO data can likely be attributed to guidelines from regulatory and reimbursement agencies, as well as encouragement from professional societies such as the American Society of Clinical Oncology (ASCO).15-17 Although guidance from regulatory and reimbursement agencies may help to standardise outcome collection across trials, it would be burdensome to generate specific outcome guidance across all disease areas. Conversely, creating broad guidance might limit relevance of the outcomes to the specific condition of interest. However, some regulatory agencies have established programmes to promote up-front communication between sponsors and regulatory agencies, allowing them to provide guidance on the collection of PROs early on in trial design. Encouragement from professional societies may influence outcome collection, but without the same kind of authority as regulatory and reimbursement agencies, these types of initiatives may fall short. Without specific guidance from these agencies, trial sponsors may have difficulty determining the best, most relevant outcomes to collect. Conducting literature reviews early on in trial design may be an efficient method to identify relevant core outcome sets, PRO measures regularly used in similar trials, and information about the validity, reliability, clinical significance, and ability to detect change of those PRO measures. This information can also be utilised in regulatory and reimbursement submissions to facilitate the agency’s review of the instrument.
Conclusions
The increased emphasis on patients’ voices in the development and value of new therapies is being reflected in CDA-AMC reviews. In order to best position new treatments, PROs should be considered starting in early phases of drug development to allow for the most meaningful data to be captured during registrational trials. These data are better able to support regulatory and reimbursement decisions that increasingly consider a more holistic perspective rather than strictly focusing on efficacy.
This article summarises Cencora’s understanding of the topic based on publicly available information at the time of writing (see listed sources) and the authors’ expertise in this area. Any recommendations provided in the article may not be applicable to all situations and do not constitute legal advice; readers should not rely on the article in making decisions related to the topics discussed.
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