Topics Workshop on the Value of Drugs: Considering the Value of Drugs and Their Evaluation from the Perspective of the Public and Patients," organized by the National Institute for Policy Studies

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Yosuke Nakano, Senior Researcher, Pharmaceutical and Industrial Policy Research Institute (PIIPRI)
Akiko Yoshida, Senior Researcher, Pharmaceuticals and Industrial Policy Research Institute

Introduction

The pharmaceutical industry is expected to continue to create innovative drugs and deliver them to patients as quickly as possible. In order to achieve this, however, it is important that the various values of pharmaceuticals created as a result of innovation be properly evaluated, and this is an issue that must be considered not only from the perspective of the pharmaceutical industry, but also from the perspective of the public and patients.

Therefore, the Pharmaceutical Industry Policy Institute (hereafter referred to as "Policy Research Institute") planned and held a workshop titled "Considering the Value of Pharmaceuticals and Their Evaluation from the Perspective of the Public and Patients" on October 20, 2021. Through lectures and discussions by prominent experts and specialists, the workshop provided an opportunity to deepen our understanding of issues and solutions from the viewpoints of the public and patients, and to think together with the participants about what the pharmaceutical industry can and should do to address them.

This report provides a summary of the presentations made at each session of the workshop and the discussions that took place during the plenary sessions.

Workshop Overview

The workshop consisted of two sessions and a plenary discussion.

First, in Session 1, under the theme of "Diverse Values of Pharmaceuticals," Yosuke Nakano, Senior Researcher of the Policy Research Institute, reported on his research on "Consideration of Diverse Values of Pharmaceuticals and Results of Public Questionnaire Survey. Then, Dr. Naka Igarashi, Associate Professor at Yokohama City University School of Medicine and Visiting Associate Professor at the University of Tokyo Graduate School of Pharmaceutical Sciences, gave a presentation on "The Value of Pharmaceuticals in Light of the Coronary Disaster and New Drug Trends".

In the following session (2), on the theme of "Evaluation of the Value of Pharmaceuticals from the Perspective of the Public and Patients," Akiko Yoshida, Senior Researcher of the Policy Research Institute, presented "Major Issues in the Evaluation of the Value of Pharmaceuticals in Japan," which was followed by a presentation by Dr. Yoshida, Representative Director of the Institute for Medical Development and Infrastructure Research, and Dr. Igarashi Naka, Visiting Associate Professor of Pharmaceutical Policy at the University of Tokyo Graduate School of Pharmaceutical Sciences. After that, Ms. Kyoko Imamura, President of the Institute for Healthcare Development Infrastructure and Visiting Professor of IT Healthcare Social Collaboration, Graduate School of Pharmaceutical Sciences, The University of Tokyo, gave a presentation on "The Current Status of PPI (Patient and Public Participation) in Japan and the Significance of PPI in Value Evaluation" and Ms. Naomi Sakurai, President of Cancer Solutions, Inc. gave a presentation on "How to Measure the Value of Medical Care? spoke on "How to Measure the Value of Medical Care" respectively.

Finally, based on the two sessions, Mr. Imamura (moderator), Ms. Igarashi, and Ms. Sakurai led a general discussion.

Together with Dr. Igarashi and his colleagues, we conducted a research study focusing mainly on "social value" among the various values of pharmaceuticals, including the current status of its outcome indicators and measurement, and a web-based questionnaire survey of the ^{public1, 2)}. The social value elements in this study were based on the nine elements of the "social perspective" among the 12 elements of value proposed in the ISPOR report3) , as well as the evaluation case study of NICE in the U.K., and the evaluation case study of the overseas organization that was triggered by the novel coronavirus infection (hereinafter referred to as "COVID-19"). Based on the 9 elements of the "social perspective" in the 12 elements of value, we also considered "reduction of care burden (mainly for family caregivers)" and "reduction of medical burden (human and material)" to be important elements, based on the evaluation by NICE in the UK and the overseas evaluation organizations triggered by the new coronavirus infection (COVID-19).

Then, based on the survey results, the social value elements were organized along the two axes of "quantifiability" and "acceptability to payers (Japanese insurers)" (Figure 2). In terms of evaluability, the first group is quantifiable and easily accepted by insurers, i.e., "relatively easy to evaluate," and includes "labor productivity" and "reduced burden of nursing care. Conversely, the second group that is 'extremely difficult to evaluate' is 'diffusion of science,' which is unclear and requires consideration of future impacts. The third group, which in some cases may have "potential for qualitative evaluation," are the other factors plotted closer to the center. With regard to the other elements, we believe that qualitative considerations could be considered by showing monetary values using, for example, a willingness-to-pay survey.

Then, we asked, "From the public's perspective, which elements of the social value of pharmaceuticals are considered important?" The results of a web-based survey on "Which elements of the social value of pharmaceuticals are important from the public's point of view? As an example of the results (without disease recall), the highest response rate was "reduced uncertainty," which is related to so-called personalized medicine and refers to the ability to predict the degree of efficacy and side effects (Figure 3). In addition, many respondents also emphasized "reduction in medical burden," meaning a reduction in the burden on medical personnel, etc., which may reflect the impact of COVID-19. When asked to recall three specific diseases (hypertension, rheumatoid arthritis, and cancer), many respondents emphasized "reduction of uncertainty" for all diseases, as was the case above. On the other hand, it was confirmed that the value factors considered important varied depending on the disease. In particular, in the case of rheumatoid arthritis and cancer, an increasing number of respondents placed importance on "reducing the burden of caregiving" for family members and others.

As described above, we reported the current status of the various values (mainly social values) of medicines that the public considers important, which also reflects the impact of COVID-19.

First, through COVID-19, many people were reminded that medical resources are finite, leading to discussions on the allocation of medical resources other than money (Figure 4). Furthermore, the idea that "not going" to the hospital itself has value in healthcare, where hospital visits had been the norm in the past, has also arisen. What can be said from this is that value in healthcare is a fluid thing, and the elements that constitute value can change.

However, just because there is value does not mean that all value elements should be asserted in the same way, but rather that shades of gray should be used to examine and develop discussions on value assessment. To this end, during the research study with the Policy Research Institute, we organized the various values of pharmaceuticals as shown in Figure 2. For example, we are currently experimenting with the possibility of creating an evaluation index that focuses on reducing the burden on healthcare workers, which was highlighted by the impact of COVID-19. We are also working on the scale of productivity loss for each disease using a web-based panel.

In terms of trends in new drugs, social interest in new drugs for dementia is growing. The informal costs of dementia (e.g., nursing care costs and family burden) are far greater than the medical costs, and also cause a decline in the quality of life of family members and other caregivers. In other words, in dementia, it is important to consider how to take into account values other than the conventional perspective of medical care. In addition, considering the broad impact of the COVID-19 vaccine, we believe that its diverse values should be evaluated and that it could be a very good opportunity to expand society's awareness of its diverse values. Based on the previous contents, the main points for evaluating various values are shown in Figure 5.

Finally, we share the results of the questionnaire that we asked participants to cooperate with at the beginning of this workshop (Figure 6). In the questionnaire, participants were asked to answer (multiple answers allowed) about the value elements of pharmaceuticals that they consider important in addition to cost and QALYs, dividing them into "value elements that they consider important" and "value elements that they consider measurable. Some value elements that are considered measurable are actually difficult to measure (e.g., reducing the burden on healthcare professionals). Therefore, it is necessary to fill in the GAPs for elements that are highly important but for which there are few measurement indicators.

We have considered the main issues in the evaluation of the "value of pharmaceutical products" in Japan from the perspective of the public and patients, and presented three points (Figure 7).

First, he explained that "opportunities for the public and patients to know" about ethical drugs are not sufficient, not only in terms of value and evaluation, but also in general, citing examples from the aspects of education and advertising regulations. Under such circumstances, the pharmaceutical industry and related organizations are working to disseminate information to the public and patients so that they can access correct information, although this is not yet sufficient, and it will be necessary to provide more opportunities for the public and patients to learn about the value of pharmaceuticals and their evaluation.

Second, we discussed "mechanisms for listening to the public and patients. He introduced various perspectives on how the public and patients' voices are heard in each country (Japan, Europe, and the U.S.). The presenter felt that in Japan, although information disclosure has been gradually opening up in recent years, it may not be sufficient in terms of public and patient participation. In Europe, however, there are opportunities for patient input not only in the development stage, but also in the approval review and all stages of post-marketing surveillance, which enables the incorporation of the voices of the public and patients4). ⁴⁾ The system and process for determining drug prices, etc ^. The systems and processes for determining drug prices differ from country to country, but in Germany and France, there are opportunities for patients to participate in the evaluation of ^value5).

In the U.S., we took a slightly different perspective and focused on "PFDD (Patient-Focused Drug Development)-meetings," an initiative to listen to the voices of patients for each disease as a form of patient engagement. As an example of such a meeting, he presented "chronic pain," a condition in which pain persists chronically without a specific cause (Fig. 86). （The most important impact of persistent pain was actually "fatigue and difficulty sleeping" (Figure 86), and the most important impact on daily life was "emotional impact, impact on interpersonal relationships, ability to be active, impact on career, etc." The results also showed that the most important impact of persistent pain was "fatigue and difficulty sleeping" (Figure 87). In addition, the patient feedback captures the patient need for hope for effective treatment options to manage chronic pain and the need for ongoing research.

Third, he discussed whether the evaluation of drug value is from the "public/patient perspective. The drug price information at the time of listing is available to the public and patients in the Chuikyo materials, and is one of the visible evaluations of value (Fig. 9). (Figure 9) However, the presenter believes that there may be insufficient information to understand what kind of value the drug has and how it was evaluated from the public/patient perspective. Although it is impossible to make a general comparison because of the wide range of differences among countries as well as systems, the presenter believes that if, for example, there is a system for listening to patients' voices as in the U.S. and Europe, the evaluation of the value perceived by the public and patients could be reflected in some form. The pharmaceutical industry also needs to communicate to the public and patients that proper evaluation of the value of drugs leads to maintaining the best possible access to innovative new drugs, and to seek their understanding.

Recently, new drug development has shifted from areas with high treatment satisfaction and drug contribution to areas with low treatment satisfaction and drug contribution (areas with high development difficulty), and an increasing number of diseases for which care as well as cure are important. Patient and public involvement is required to have an effective impact in terms of development and marketing, and AMED is also promoting PPI with a focus on encouraging investigator-led research, and has published a PPI guidebook. In other words, we are entering an era in which "patient and citizen involvement" is being promoted in public research.

According to the results of a questionnaire survey conducted by the Pharmaceutical Manufacturers Association of Japan (Fig. 10), Japan is inferior to Europe and the U.S. in all five major categories of whether or not patient-centered development is taking place. In Japan, there are few opportunities for patients and citizens to participate and exchange opinions. Furthermore, while the institutional characteristics of the Japanese system allow for approval and listing of drugs on the NHI drug price list without much patient commitment, we believe that there may be unmet needs hidden in the system. Another characteristic of Japanese patient groups is that they are often voluntary and small, making it difficult for them to speak out in a unified manner. As for a mechanism for listening to the voices of patients, the composition of the Chuikyo committee members shows that there is only one patient slate, and I believe that this is not a mechanism for directly conveying the voices of patients.

Next, as an example of patient engagement efforts overseas (Figure 11), the ^PARADIGM7) has established a patient engagement process and tools for three objectives (prioritization of research, design of clinical trials, and early consultation with authorities and drug pricing organizations). In addition, we believe that "creating opportunities for the exchange of ideas" will help promote PPI in all aspects, and we have translated the "Agreement Guidelines for Patient Involvement" from the PARADIGM development tool, which is available in the public domain, for your use. Furthermore, the ^{EUPATI8)Guidance9)} (HTA) includes patient engagement at all stages, and we hope this will be the case in Japan.

One of the challenges of patient participation in HTA is who will establish a system to enable patient participation. Prior education and standardization of understanding are important for participation in discussions, and it is also necessary to consider who should participate, organizing stakeholders such as individual patients, caregivers, advocates, patient (support) groups, and patient experts. As a matter of fact, not all patient groups and support groups are conscious enough to participate in the discussion. However, it is not necessarily true that only organized groups can express their opinions. In addition, if there are multiple patient groups for the same disease, how to evaluate conflicts of interest among participating patients (groups) must also be ensured. There are various issues to be addressed, but as long as it is essential to discuss what the burden should be borne by society, the participation of patients (organizations) and citizens (organizations) is necessary.

Values are indeed diverse, and how to share values with society, the community, and individual people is important. In particular, it is important for public goods to be accountable to society and to share values with society by using easy-to-understand language when explaining them. However, when I became a patient, I realized that in healthcare, everything is decided before we know it, and there is no sharing of these values. Even as a patient, I would like to know about evidence information and costs of treatments and drugs, including their future potential. In addition, I feel that the contribution of medicine to labor productivity is easily understood by society, and I hope that social sharing of values in medicine will progress.

Efforts to "make the most of the patient voice" are gradually changing in Japan, although it lags behind Europe and the United States. However, while the incorporation of the patient's voice has been talked about in various terms (patient/citizen engagement, research advocacy, patient centricity, etc.), we feel that there are things that can be done in a more rudimentary manner. For example, there was a case in which, in response to the fact that only information for medical professionals was available on stable supply, we submitted a written request for the presentation of information for patients, and finally the information was presented. While we talk about "patient-centeredness," we sometimes feel that doctors and hospitals are the main focus, which is disappointing. In addition, indicators such as whether the patient had an appetite or enjoyed a meal as a state of mind may be more appealing to patients than measuring total body muscle mass or grip strength as an evaluation of a drug's effectiveness.

Currently, EU guidance (EUPATI) is being utilized (Fig. 12), and there are an increasing number of cases in which patients' voices are incorporated in the later stages of R&D. However, since it is difficult to return to the original state once progress has been made, patient involvement from an earlier stage is desirable, and further development is expected in the future.

On the other hand, pharmaceutical companies are also encouraged to reconsider at what stage of the research process they are implementing patient involvement (research selection, clinical trial development, clinical trial implementation, NHI/insurance listing, and post-marketing management decision-making).

Finally, as shown in Figure 13, please remember that HTA (proper innovation assessment and reduction of unnecessary costs), PPI (promotion of PPI to drug evaluation), and PRO (introduction of PRO to drug evaluation) are all connected in a balanced manner, without isolating just one. I would like to see them incorporated. Value sharing is an activity that makes the public happy, and it is important to increase its accuracy.

The roots of PPI activities began with HIV (infectious diseases) ¹⁰⁾, and now that we have encountered COVID-19, we need to rethink its "significance" and the phrase "Don't decide about us without us" (used in the process of formulating the Convention on the Rights of Persons with Disabilities), which is exactly what we should do. This is exactly the point.

Overall Discussion

1. among the various values, what are the important values for the public/patients?

Mr. Igarashi, based on the results of the public survey on the various values of pharmaceuticals conducted during the COVID-19 epidemic (many people considered the value of "reducing the burden on healthcare professionals" important), suggested that if the survey had been conducted before the COVID-19 epidemic, the viewpoint of "reducing the burden on healthcare professionals" would have emerged as an important value. If the survey had been conducted before the COVID-19 epidemic, it is assumed that the perspective of "reducing the burden on healthcare professionals" would not have emerged as an important value. In other words, the value of pharmaceuticals can change depending on the times and social environment, and it is necessary to determine the important values for the public and patients in accordance with the "current trends.

Mr. Sakurai shared his opinion that in considering "important values for the public and patients," it is necessary for patients to consider the value of pharmaceuticals from the patients' viewpoint and then return to the public's viewpoint (objective viewpoint) to see how their claims are seen from the outside. In addition, in relation to the earlier survey of the public, given the current situation in which many people have a history of COVID-19, another "important value" may emerge if the survey is limited to people with a history of the disease and their family members, he asked. The question was also raised.

Dr. Imamura stated that COVID-19 is an acute infectious disease and that the data necessary for value assessment are easy to obtain, and that since sequelae after COVID-19 infection are also considered problematic, he hopes for the development of future surveys and research in Japan as well.

2. what should be done to ensure that important values for the public/patients are valued?

Mr. Igarashi advised that in the discussion of various value evaluations, we should clarify where the problem lies (in the product, in the evaluation index, or in both) when evaluation is difficult within the existing framework, so as not to cause the misunderstanding that the discussion is in favor of pharmaceutical companies. The workshop was also a good opportunity to discuss the issues and to discuss the future of the project. He also argued that there are more and more opportunities to discuss the value and evaluation of pharmaceutical products, including this workshop, and that we need to make progress in the discussion at this time when there are concrete examples of COVID-19 treatments and vaccines and dementia drugs, which are of great interest to people.

Mr. Sakurai mentioned that the European EMA recently provided a detailed and easy-to-understand explanation of the approval process for vaccines based on the case of COVID-19. He shared that the story was familiar to us and that he was impressed by the development story of the vaccine developed and approved in an extremely short period of time and realized the value of the product. The story is familiar to us. On the other hand, however, some of them commented that they felt frustrated as a nation that there is no opportunity to share such information in Japan due to advertising regulations and other reasons.

In addition, he commented that the NHI drug price system and cost-effectiveness evaluation system tend to be discussed in comparison with those in Europe and the U.S., but that Japan should consider its own unique way of doing things, taking into account the country's unique characteristics (full nursing care system and super-aging society). In conjunction with this, Mr. Igarashi stated that there is an effort to create a QOL measurement index that takes advantage of such Japanese characteristics, and that useful data originating in Japan against the backdrop of the super-aging society could be disseminated overseas.

Dr. Imamura commented that the evaluation of the value of pharmaceutical products in Japan tends to be directed toward physicians, and that the approach should take into account the evaluation of patients as end-users, with the patient's voice being included from the early stages of research and development.

What should the pharmaceutical industry do?

Dr. Igarashi advised that it is impossible to quantify all the various values, but it is also incorrect to say that there is no value if it cannot be quantified, and that it is desirable to make concrete proposals from where one can. He also advised that it is important for the pharmaceutical industry to unify its intention of which value to claim first, and to proceed one by one while investing resources intensively in this area, and not to claim prices based on value without substance.

Mr. Sakurai mentioned that when the cost-effectiveness evaluation system was introduced, he hoped that light would finally shine on areas that had not been illuminated (patients could participate in value evaluation), but that this did not happen. He encouraged pharmaceutical companies to take on new challenges without being bound by the rules of the regulatory authorities. He also suggested that, in promoting patient participation in drug development, pharmaceutical companies should first read their own protocols to see if they are written in language, expressions, etc. that are truly easy for patients to understand.

Finally, Dr. Imamura concluded by saying that although there may be various issues, there is nothing that cannot be done, and that pharmaceutical companies, as well as the pharmaceutical industry, should take one initiative at a time.

(*As a means of conveying the content of this discussion more clearly, a graphic recording (a technique of drawing pictures and simple text) was used to create a diagram (Fig. 14), which should be referred to as well.)

Concluding Remarks

The following is a brief description of the suggestions the authors obtained through this workshop. First, although pharmaceuticals have a variety of values, the values of pharmaceuticals can change depending on the times and social environment. It is essential to determine the important values for the public and patients, and to use the opportunities presented by the times to deepen the analysis and discussion of new value evaluation. It is also necessary for the pharmaceutical industry to be unified in its intention to make claims with concrete examples and their rationale rather than ideologically, and to decide from which value to make such claims.

On the other hand, in order to evaluate values important to the public and patients, it is essential to involve the public and patients (PPI), but the current situation in Japan lags behind that of other countries. Rather than simply following in the footsteps of other countries, it would be good to consider Japan's own unique approach, taking into account the country's characteristics (universal health care coverage, full long-term care system, super-aging society, national character, etc.). As a result, it would be desirable for the voices of patients to be included from the early stages of research and development, and for approaches to be realized that take into account the evaluations of patients as end users. And we, the pharmaceutical industry, are expected to boldly take up challenges without being bound by regulatory frameworks.

After the workshop, we received feedback from the participants in a questionnaire. The organizers were very pleased to receive a high evaluation of the workshop as a whole (90% of the participants were "satisfied" or more). In addition, free comments included: "In the future, discussions should involve a wide range of stakeholders, including healthcare professionals, patients, caregivers, and government officials," "It is necessary to raise the awareness of pharmaceutical companies," "It is necessary to create a system that allows many citizens to think about pharmaceuticals as their own personal matters," "The government and companies need to create a system that is easier to understand for citizens and patients," and "It is necessary to create a system that allows many citizens to think about pharmaceuticals as their own personal matters. The government and companies must also make efforts to provide information that is easier to understand to the public and patients.

In addition, more than 30% of the respondents expressed their expectations for future projects related to the "value of medicine" that are not limited to pharmaceuticals but have a broader perspective. We would like to utilize the lessons learned and suggestions from this workshop, including the content of this questionnaire, in our future research and surveys.

Finally, we would like to take this opportunity to thank all the speakers and others who contributed to the workshop, as well as all the participants, for their hard work and cooperation.

(Supplement) Figure 14 is based on the personal perception of the author (Ms. Kanna Yoshikawa) and was prepared from a bird's eye view of the overall discussion.

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