FormalPara Key Points for Decision Makers

Patients can be put at the centre of health technology assessments (HTA) by ensuring HTAs include robust research about patient aspects and/or supporting patients and their representatives to participate during the HTA process.

Patients can provide unique, experiential knowledge to HTA that can complement clinical research, helping overcome uncertainties in clinical evidence and inform determination of value.

With effective patient involvement, HTA can inform patient-centered healthcare policy, ensuring fair and transparent allocation of resources informed by the needs, preferences and experiences of patients.

1 Is Health Technology Assessment (HTA) Compatible with Patient Centeredness?

Health systems funded by taxation, social insurance, personal/employer insurance or private fees may seem very different but they often align with the ‘six pillars of quality’ to deliver effective, safe, patient-centered care in an efficient, timely and equitable manner [1]. Another area of alignment is the challenge resulting from increasing demand [2] that often exceeds available healthcare resources. This requires difficult choices about who to treat, with what intervention, in what setting and for how long [3].

Health technology assessment (HTA) is a field of scientific research intended to inform policy making about a major area of expenditure in healthcare, namely the introduction and use of health technologies [including medicines, devices, diagnostics, surgical procedures, vaccinations, organization of health systems, digital applications (apps), patient education and other health interventions]. HTA International (HTAi) [4] states that HTA is a multidisciplinary field that addresses the clinical, economic, organizational, social, legal and ethical impacts of a health technology, considering its specific healthcare context, as well as available alternatives, and that its methods should be transparent, systematic and rigorous.

The goals of patient-centredness, such as providing more appropriate care, improving safety, reducing error, meeting patient expectations and improving the public accountability of healthcare [5], are compatible with HTA. Often an individual person is imagined when describing patient-centred care in order to broaden the medical perspective beyond a set of symptoms. HTA further broadens the lens to consider the needs of an entire society to wisely allocate health resources.

HTAs can contribute to patient-centred healthcare when they include patient participation and take account of patients’ needs, preferences and wider social contexts when forming recommendations. In HTA, the use of patient-centred approaches may enable HTA researchers and expert committees to understand the needs of patient populations. However, increasingly short timelines for HTAs, and failure to address the burden of participation for patients and patient groups, provide substantial challenges to realizing the goal of informing evidence-based patient-centred policy.

In this commentary, we reflect on the evolution of HTA over the past two decades and the impacts this has had on patient involvement, from a range of stakeholder perspectives and regions. We explore the need to define the goals of patient involvement in HTA more clearly and critically examine processes for patient participation and research into patient aspects to ensure that HTAs inform patient-centred healthcare.

2 Evolution of HTA: Implications for Patient-Centredness?

In the 1990s, HTA was often used to compare all possible health technologies for one condition. Secondary and primary research methods from a range of disciplines, including evidence-based medicine, economics, political science, philosophy and social science, were used to provide robust summaries of the evidence relating to potential impacts of using the health technologies. The intention was to provide decision makers with policy alternatives, not to mandate use of a technology.

Scotland adopted the Danish model of HTA, which considered clinical effectiveness, economic issues, organizational issues and patient aspects [6]. Given a political imperative to have a patient focus, patient aspects were studied as rigorously as the three other domains. A review of the international literature was undertaken to determine patients’ experiences, perspectives and preferences in relation to the technologies, and complemented by primary research with Scottish patients. This research identified issues not reported in clinical research, such as difficulties in accessing treatment [7] or patient misconceptions about the purpose of technologies [8]. This ‘patient-based evidence’ was considered alongside the evidence from the other three domains, and informed the HTA research as it developed (outcomes of importance, form of economic modelling, organizational issues to be addressed, etc.). In addition, a representative from a relevant patient organization participated in each HTA as a member of the interdisciplinary expert advisory group, where dialogue with HTA researchers helped shape the HTA research and interpret findings.

Patients were recognized as having unique, experiential knowledge that could complement clinical research. They could provide insights into care pathways, explain the benefits and challenges of using existing health technologies, and share experiences or expectations of new health technologies.

By 2000, there was increasing concern that such research-based HTAs took too long and cost too much. Policy makers felt that HTAs had complex language, included data of questionable quality, lacked real-world applications, had too narrow a focus and were not timely [9]. Around this time, HTA bodies were established in Australia and England that did more than inform policy makers—their recommendations led to mandatory reimbursement decisions about new medicines. To do this, they had to be shorter, more timely and targeted. As a consequence, these HTAs focused on issues of clinical and cost effectiveness, not the wider organizational, social, legal and ethical impacts and the patient aspects. Furthermore, as time pressures became greater, HTAs moved from systematic literature reviews of the clinical evidence to more rapid reviews or submissions of evidence from health technology developers. In parallel, the few HTA agencies that recognized the need for patient involvement in these more rapid HTAs moved away from the lengthy process of primary and secondary research into patient aspects, to submission processes that required patient groups or individual patients to submit information to the appraisal [10, 11].

During this period, improvements in computing capability enabled complex economic modelling. Cost-utility analysis with modelling of uncertainties became the backbone of defining value in HTA in many countries. With this impetus, value was defined in terms of the quality-adjusted life-year (QALY), a metric based on a generic quality of life (QoL) instrument that could be used across all health conditions, allowing assessors to compare the ‘value’ of interventions across diseases. In order to decide which medicines should be reimbursed or recommended for use, the cost of achieving one additional QALY was calculated and a maximum cost threshold could be set. Those below the cost threshold were likely to be reimbursed and those above were only likely to be reimbursed if there were mitigating factors.

In the early 1990s, methodological concerns were raised about biases inherent in QOL analyses [12], but, as the widespread use of cost-utility analysis shows, HTA agencies have been content to use them despite issues with missing data, challenges mapping QoL in different populations to disease states, and lack of sensitivity of the instruments. Today, concerns continue to be raised about whether the QALY truly captures the value of an intervention for all diseases [13, 14].

It is not just the QALY that creates challenges in economic models—the models require input from a range of sources, such as well-conducted clinical research through to real-world data, about the prevalence and natural course of a disease and the associated costs and consequences of the health technologies compared. As a result, uncertainties are inherent. Therefore, although cost-utility analysis can be an important tool to discuss value in HTA, the wider domains of HTA should also be considered to understand all the potential impacts of a health technology. Additional factors or ‘decision modifiers’ have been documented in some HTA systems that may lead to approval of a technology with a cost/QALY above a usual threshold in special circumstances, such as at end of life, where there is high unmet need, where there is substantial gain in survival or QOL, or where it is a bridge to definitive therapy [15]. The question is, how do patients’ perspectives contribute to these deliberations about value?

3 Clarifying the Purpose of Patient Involvement in HTA

Patient involvement in HTA comprises research into patient aspects, which produces patient-based evidence, and patient participation in the HTA process [16, 17]. Some would say that HTA is a scientific discipline and patients and their representatives who take part only provide anecdotal and biased input [18]. However, HTA is meant to inform policy and as such should include the perspectives of a broad range of stakeholders (particularly those affected by the decision) to ensure that the resulting recommendations are better informed and democratically accountable [16, 19].

As we have elucidated over the past decade, even as scientists we should want to involve patients in our work because they have unique knowledge that can help us frame our HTAs to study the outcomes that really matter to patients and interpret the results to understand value [20]. When there is uncertainty in the best available evidence about clinical and cost effectiveness, patient-based evidence and patient input can help us determine the veracity of assumptions and develop an understanding of all aspects of value [17, 21].

This does not necessarily mean that ‘the patient’ is at the centre of HTA. HTA is about the wise allocation of resources for all those who use the health service. In fact, HTA should be centred (or fair) to all users of the health system. To be fair, the needs, preferences and experiences of patients need to be fully understood and judged in line with societal values, whatever the form of HTA—full or rapid. This can be achieved by supporting patients to participate in HTAs using the internationally recognized quality standards for patient involvement in HTA presented in Table 1, and encouraging HTA bodies and health technology developers to invest in targeted research to develop patient-based evidence that will focus research and help resolve uncertainties in other evidence.

Table 1 HTAi quality standards for patient involvement in HTA (HTAi, 2014)
Full size table

Therefore, patient involvement should encompass research that develops robust patient-based evidence to be considered alongside the clinical and economic evidence in HTA. It should also support the meaningful participation of patients and their representatives in HTA appraisal processes to contribute to deliberative discussions to help elucidate evidence in the local context. Ideally, this should be done as dialogue, not as one-way input [10, 22].

4 Examples of Patient Involvement Impacting HTA Recommendations

As HTA is a complex process of evidence synthesis and deliberative critical review, it is a challenge to tease out how one element, such as patient involvement, has impacted a recommendation or decision. A recent study undertook 24 interviews of HTA committee members and expert contributors in Canada and concluded that patient input can ‘put a human face on the evidence’, address gaps in clinical trials and contribute to deliberative discussions of trade-offs. Below are some specific examples to show how patient input can impact HTA recommendations.

Research shows that patients help identify outcomes that are important to them [23]. This can influence committees to recommend a technology when clear benefits are shown on those outcomes, or, alternatively, not to recommend if benefits are limited to outcomes not perceived to be important to patients. This was shown in the Canadian Agency for Drugs and Technologies in Health (CADTH) review of budesonide MMX for ulcerative colitis (UC) [24]. Similarly, in NICE’s appraisal of vedolizumab for UC, patients told the Appraisal Committee that surgical interventions were deemed unacceptable for young people due to the impact on fertility and their irreversibility and life-long impact [25]. Treatment with vedolizumab gave people complete remission and allowed them to return to activities of daily living, including working and studying. The impact of full remission and avoiding surgery on the patient’s QOL was formally acknowledged by the committee when drawing up its recommendations.

Patients often contribute experiences that are not part of the evidence found in clinical research. This is particularly valuable when clinical evidence is sparse or is based on biomarkers. For example, the CADTH review of Kuvan for phenylketonuria identified significant reductions in phenylalanine, but patients explained the impact this had on their ability to eat a wider range of food and their general health, thus improving QOL [26]. In the NICE appraisal of insulin pump therapy for treating type 1 diabetes in adults and children, an evidence base existed for effectiveness in adults, but not in children. Parents of children with diabetes told the committee how pumps can revolutionize both the care and QOL for children with diabetes [27]. This allowed the committee to make a positive recommendation about the use of pumps for children, despite a lack of clinical evidence.

Patients often add insights into how the clinical trial conditions differ from the local healthcare setting that can inform judgements about the veracity of the assumptions in the economic modelling of cost effectiveness. For example, in the case of primary progressive multiple sclerosis, patients explained that the disease is characterized by a continuous worsening of the disease. This was contrary to the company’s assumptions in the model and supported the reanalysis performed by CADTH [28]. When NICE was appraising interventions for age-related macular degeneration, the modelling used the evidence-based assumption that loss of sight in one eye has little impact on someone’s QOL. This assumption was challenged by the patient community, who indicated the significant impact on activities of daily living and QOL related to loss of binocular vision. As a consequence, the committee reconsidered the cost effectiveness of starting treatment with the loss of sight in one eye [29].

Patients can question or confirm assumptions on interpretation of evidence. For example, in the CADTH review of Truvada for the prevention of HIV, female sex workers explained issues they face in relation to sexual assault and financial and behavioural pressures that lead to condomless intercourse [30]. Patients explained to NICE that prosthetic replacement of the temporomandibular allowed them to return to activities of daily living. The evidence presented conventional outcomes such as speaking and eating, but patients explained that other outcomes such as being able to sing and kiss properly were also important [31].

5 Burden Versus Benefit of Patient Input in HTA

We encourage consistent, transparent involvement of patients in individual HTAs and in the development of HTA processes. However, from our differing perspectives, we question whether this should be for all HTAs. For simple diagnostic tests or medical devices applied as part of a more complex interventional procedure, will patient knowledge add significantly to the other evidence available, and will patients know what intervention they have received? Could an advocate representing all patients ensure that good standards of care are considered, including issues of equity of access and clear communication? Such considerations are now being addressed explicitly for all non-medicine HTA topics in Scotland.

When we do encourage patient groups, patient experts or individual patients to get involved in our HTA processes, we need to be explicit about what can and cannot be achieved by their involvement. We need to be clear that in some circumstances the evidence submitted to the HTA results in estimates of value for money way above the usual threshold for acceptance (willingness to pay). Then, no matter what disease modifiers are considered, or additional patient input or patient-based evidence is provided, the value of the technology will not be proven or the cost will be too high for the benefit demonstrated.

The principles and processes of patient involvement have an inherent value. However, meaningful and effective patient involvement does not necessarily mean that a health technology will be reimbursed [32], just as a doctor’s patient-centredness cannot be evaluated as a patient receiving the treatment they want [33]. This can be a challenge for patient groups who invest time and resources to participate in an HTA at the request of an HTA agency. We need to resolve this disconnect and focus on patient involvement activities that can influence determination of value, not just make this another tick box exercise of ‘patients included’.

Some HTA processes allow organizations or individual patients to participate in public consultation processes about draft HTA reports. Hundreds or thousands of responses may be received [34] but it is not clear how such responses are considered or summarized or what influence they have. Some HTA processes allow submissions on a template designed specifically for individual patients or patient groups. These templates have been honed over years of use and request information that appraisal committees have found valuable in the past, such as issues of living with the disease and pathway of care in the healthcare system, experiences of existing health technologies, and experiences and expectations of new technologies.

In the Common Drug Review and pan Canadian Oncology Drug Review programmes at CADTH, over a 6-year period from June 2010, 532 patient group submissions were received from 137 patient groups. One-quarter of these provided five or more submissions during that period [35]. Although these submissions are required in a short timeframe (7 weeks), most collected information from a range of patients in several ways, including surveys, interviews and gathering of informal insights. These studies were either conducted specifically for the particular HTA submission or undertaken previously for other purposes [36].

Patient groups have been pleased to be able to contribute to HTAs in such a structured manner. They value the support provided by HTA agencies in terms of training and dedicated staff contacts [37, 38], but want to have more clarity about the processes for patient involvement and integration of experiential and scientific knowledge [39]. As the HTAi Values and Standards demonstrate [40], these are essential elements to good patient involvement. However, the burden on groups that have no paid employees, little understanding of HTA, or who are asked to contribute to several HTAs in 1 year can be overwhelming. If HTA agencies do not provide guidance and support to participants, the usefulness of patient input may be limited, wasting the time of both patients and the agency and frustrating the expectations of all.

Until CADTH began the process of feedback in 2014, no HTA agency provided patient groups with feedback on the difference their submission made to the deliberations of the appraisal committee, and the resulting recommendations. An early analysis revealed that in 15 of 20 patient input submissions to CADTH following feedback, patient groups incorporated at least one item of feedback, including methods to collect data, direct patient quotations and more detailed explanations. Generally, patient groups valued the personalized feedback, however some groups explained time and resource constraints inhibited their ability to fully implement the suggestions offered [41]. NICE has now followed suit [42], and all are finding it helpful to review what makes a difference to the appraisal committee’s deliberative discussions. This critical review of patient input by HTA agencies should be encouraged, not criticized, but to discuss in collaboration with patient groups what input they can optimally provide within their limited resources. Some may question the cost to HTA agencies of providing the feedback, but given the patient group’s investment in the process, it is surely an incentive to the patient group to have feedback, and indeed a right in a transparent process. Furthermore, if patient input is really valued by an HTA body, they would surely do everything possible to ensure that patient input is as relevant and useful as possible. This requires shared learning and knowledge building on the processes, the environment, and how to channel the unique experiential knowledge of patients.

Diverting the scarce resources of patient groups into one policy area that may only affect a small proportion of the patients they represent may take significant time and resources and result in no change to patient access to a technology. In future, they may prioritize their own resources differently and we need to consider how we can provide appropriate resources for patients to participate, whatever the HTA decision.

HTA agencies do not pay patient groups for their submissions and only a few agencies offer payment for attending committee meetings. HTA agencies pay for their staff and, in some cases, their expert reviewers, hence a big question arises about how patient involvement in HTA should be funded as concerns obviously arise about too much funding from health technology developers and the bias that may introduce. It is unrealistic to expect patient groups to fund the cost of HTA engagement when they are often struggling to obtain funding for their essential activities and rely heavily on volunteer contributions. Meanwhile, HTA agencies fund external bodies or their own staff to review the clinical and cost-effectiveness evidence. Hence, why should patient groups have to pay for the privilege of providing their knowledge, which aims to enhance the HTA decision-making process?

Discussions among some HTA agencies and patient groups are underway regarding the possibility of HTA agencies using previously submitted patient group submissions to reduce the burden on patient groups [43]. Information such as the background to living with a disease, epidemiology and experiences with existing treatments may be relevant to several submissions. Alternatively, there could be easier ways of obtaining that information from patients—rather than asking patient groups to make a submission, the onus could be on the HTA body to elicit that information, akin to the Patient-Focused Drug Development workshops of the US FDA [44].

6 Better Research to Develop Patient-Based Evidence

With more rapid HTAs, research to produce patient-based evidence has diminished [11]. It was too time-consuming to perform a synthesis of qualitative evidence or primary study that required ethical approval. However, this work could be undertaken by health technology developers earlier in the development of the health technology, or new methods for rapid qualitative evidence synthesis could be developed.

Research into patients’ aspects should be encouraged, but the burden of primary research into patient aspects must be carefully considered. Developing a new patient-centred outcome or undertaking a discrete choice experiment is a costly affair. Furthermore, while we have seen huge leaps in terms of the transparency of clinical research protocols and results as a result of legislation [45], we do not see the same for research to produce patient-based evidence. Perhaps this is because this work is seen as providing commercially valuable insights, not unlike the confidentiality that is often associated with the detail of an economic model. This has two consequences. There is duplication of work and patients’ knowledge is not used optimally. Hence, research to produce patient-based evidence should have clear goals, be of good quality, and be published.

Clinical research is meticulously planned to meet regulatory (and HTA) needs in as efficient a manner as possible. The FDA has produced a helpful discussion document [46] that reflects on how to collect comprehensive and representative information from patients that also provides good food for thought in relation to HTA.

Health technology developers create evidence generation plans for clinical research and real-world data to meet the needs of regulators and HTA early in the lifecycle of the technology. Some are undertaking research into patient aspects using a variety of approaches, from analysis of social media to complex patient preference studies. However, the range of research is often less well-planned than clinical research, where the regulatory and HTA requirements are clearer [47].

In recent user agreements, the FDA has encouraged rigorous development of patient-centred (focused) outcomes to inform labelling [48] and patient preference research [49]. The FDA now goes one step further and requires a section on patient-based evidence in each submission [46]. HTA bodies need to follow suit and revert to the HTA principles of two decades ago to reinstate the explicit consideration of patient aspects, both in evidence submissions and HTA guidance [50].

Furthermore, as HTA bodies have had to develop new methods for rapid reviews of clinical evidence, there is a need to develop rapid qualitative evidence synthesis for patient aspects [51]. A recent review shows that such rapid qualitative evidence syntheses are valued by a range of decision makers, but they are rarely published in peer-review journals [52]. Thus, more work needs to be undertaken to evaluate their potential and limitations.

Other agencies are exploring the use of quantitative methods to understand stated preferences via discrete choice methods [53] or analytical hierarchy processes [54]. These are helping to support discussions about what matters to patients, but their use in economic models to derive utilities is still open to debate.

Research into patient aspects should be likewise planned and limited to areas that will really make a difference, and, like clinical research, undertaken with the highest methodological rigor, and reported widely.

7 Conclusion: Achieving Value in Patient Involvement

The objectives of patient involvement should be clarified for each HTA, and involvement approaches should then be honed to the specific HTA. However, as we have reflected in this article, there is no gold standard. Patient involvement is a journey. It evolves with processes, capabilities, dialogue, and changing expectations.

Patient involvement is a costly exercise for all those involved and as we look for value in healthcare, patient involvement must add value and be cost effective [55]. Some HTA agencies invest in research to evaluate their processes for involving patients in HTA, but work in this field is limited [56]. However, it is essential that we have dialogue about what works well and what could be improved. We need to offer training and constructive feedback, and there needs to be transparency about how we use patient input and balance patient-based evidence alongside other forms of evidence. Ideally, this should lead to clear guidelines from HTA agencies about the development of patient-based evidence, similar to the guidance that is produced for economic evaluation, as well as clear policies and processes to support patient participation.

This should create efficiencies for all stakeholders—health technology developers investing in research to develop patient-based evidence, patient groups who get involved in HTA, and HTA bodies who have limited resources to invest in patient involvement.

Most of all, we need to encourage patient involvement in HTA in countries where patients and their representatives are currently excluded, which is the case in the majority of countries around the world. In these countries, concerns about involvement need to be discussed and patient groups should work with HTA bodies and higher-level policy groups to encourage the use of published research into patient aspects, and develop plans for patient participation that can demonstrate the value of local patient knowledge. Each healthcare system needs its own bespoke system, but we can learn from others and share as much as we can.

An area where this is of paramount importance is the proposed legislation for HTA in Europe [57]. Stakeholder involvement is noted as being important, but plans indicate stakeholders (including patient groups) will have an observer role on the senior body, the Coordinating Group. To date, there are no details of the patient involvement that could occur in the work to develop joint clinical assessments and joint scientific consultations, and in the wider policy and process development. However, patient groups are articulating their aspirations throughout the current legislative debates on the proposal, as effective patient involvement in HTA at the European level could lead to major efficiencies in the Member State processes and burden on national patient groups.

Regardless of how HTA evolves, we need to ensure that its processes are robust, inclusive and evidence-based, genuinely incorporating patients’ perspectives and experiences. HTA can then help to create patient-centred healthcare policy that ensures the fair and transparent allocation of resources informed by the needs, preferences and experiences of patients.