Patient Perspectives on the Value of Patient Preference Information in Regulatory Decision Making

Background: There is increasing interest in involving patient preferences for benefits and risks in regulatory decision making. Therefore, it is essential to identify patient perspectives regarding the value of patient preference information (PPI). Objectives: The aim of this study was to explore how patients with rheumatoid arthritis (RA) value the use of PPI in regulatory decision making regarding medical products. Methods: Regulators and patients with RA were interviewed to gather initial insights into opinions on the use of PPI in regulatory decisions regarding medical products. The interviews were used to draft and validate the interview guide for focus groups with patients with RA. Participants were purposively sampled in collaboration with the Swedish Rheumatism Association in Stockholm and Uppsala. Each focus group consisted of three to six patients (18 in total). All interviews were audio-recorded, transcribed verbatim, and analysed using content analysis. Results: According to the participants, PPI could lead to regulators considering patients’ needs, lifestyles and well-being when making decisions. PPI was important in all stages of the medical product lifecycle. Participants reported that, when participating in a preference study, it is important to be well-informed about the use of the study and the development, components, administration, and risks related to the medical products. Conclusions: Patients thought PPI could be valuable to consider in regulatory decisions. It is essential for patients to be well-informed when asked for their preferences. Research on information materials to inform patients in preference studies is needed to increase the value of PPI in regulatory decision making

How can patient preferences be used and communicated in the regulatory evaluation of medicinal products? Findings and recommendations from IMI PREFER and call to action

Objective: Patients have unique insights and are (in-)directly affected by each decision taken throughout the life cycle of medicinal products. Patient preference studies (PPS) assess what matters most to patients, how much, and what trade-offs patients are willing to make. IMI PREFER was a six-year European public-private partnership under the Innovative Medicines Initiative that developed recommendations on how to assess and use PPS in medical product decision-making, including in the regulatory evaluation of medicinal products. This paper aims to summarize findings and recommendations from IMI PREFER regarding i) PPS applications in regulatory evaluation, ii) when and how to consult with regulators on PPS, iii) how to reflect PPS in regulatory communication and iv) barriers and open questions for PPS in regulatory decision-making.Methods: PREFER performed six literature reviews, 143 interviews and eight focus group discussions with regulators, patient representatives, industry representatives, Health Technology Assessment bodies, payers, academics, and clincians between October 2016 and May 2022.Results: i) With respect to PPS applications, prior to the conduct of clinical trials of medicinal products, PPS could inform regulators’ understanding of patients’ unmet needs and relevant endpoints during horizon scanning activities and scientific advice. During the evaluation of a marketing authorization application, PPS could inform: a) the assessment of whether a product meets an unmet need, b) whether patient-relevant clinical trial endpoints and outcomes were studied, c) the understanding of patient-relevant effect sizes and acceptable trade-offs, and d) the identification of key (un-)favorable effects and uncertainties. ii) With respect to consulting with regulators on PPS, PPS researchers should ideally have early discussions with regulators (e.g., during scientific advice) on the PPS design and research questions. iii) Regarding external PPS communication, PPS could be reflected in the assessment report and product information (e.g., the European Public Assessment Report and the Summary of Product Characteristics). iv) Barriers relevant to the use of PPS in regulatory evaluation include a lack of PPS use cases and demonstrated impact on regulatory decision-making, and need for (financial) incentives, guidance and quality criteria for implementing PPS results in regulatory decision-making. Open questions concerning regulatory PPS use include: a) should a product independent broad approach to the design of PPS be taken and/or a product-specific one, b) who should optimally be financing, designing, conducting, and coordinating PPS, c) when (within and/or outside clinical trials) to perform PPS, and d) how can PPS use best be operationalized in regulatory decisions.Conclusion: PPS have high potential to inform regulators on key unmet needs, endpoints, benefits, and risks that matter most to patients and their acceptable trade-offs. Regulatory guidelines, templates and checklists, together with incentives are needed to foster structural and transparent PPS submission and evaluation in regulatory decision-making. More PPS case studies should be conducted and submitted for regulatory assessment to enable regulatory discussion and increase regulators’ experience with PPS implementation and communication in regulatory evaluations

Patients accept therapy using embryonic stem cells for Parkinson’s disease:a discrete choice experiment

Background: New disease-modifying ways to treat Parkinson’s disease (PD) may soon become a reality with intracerebral transplantation of cell products produced from human embryonic stem cells (hESCs). The aim of this study was to assess what factors influence preferences of patients with PD regarding stem-cell based therapies to treat PD in the future. Methods: Patients with PD were invited to complete a web-based discrete choice experiment to assess the importance of the following attributes: (i) type of treatment, (ii) aim of treatment, (iii) available knowledge of the different types of treatments, (iv) effect on symptoms, and (v) risk for severe side effects. Latent class conditional logistic regression models were used to determine preference estimates and heterogeneity in respondents’ preferences. Results: A substantial difference in respondents’ preferences was observed in three latent preference patterns (classes). “Effect on symptoms” was the most important attribute in class 1, closely followed by “type of treatment,” with medications as preferred to other treatment alternatives. Effect on symptoms was also the most important attribute in class 2, with treatment with hESCs preferred over other treatment alternatives. Likewise for class 3, that mainly focused on “type of treatment” in the decision-making. Respondents’ class membership was influenced by their experience in treatment, side effects, and advanced treatment therapy as well as religious beliefs. Conclusions: Most of the respondents would accept a treatment with products emanating from hESCs, regardless of views on the moral status of embryos. Preferences of patients with PD may provide guidance in clinical decision-making regarding treatments deriving from stem cells.</p

Getting a Say : Bringing patients’ views on benefit-risk into medical approvals

The focus of this thesis is a new quantitative approach to consider patient preferences on benefits and risks in medical approvals. The overall aim of this thesis was to explore how patient preference information may be relevant to regulatory marketing authorisation decisions. Study I provides an overview of the different decision-processes of industry, regulatory agencies and health technology assessment bodies/reimbursement agencies along the medical product lifecycle. In total, 15 decision points with the potential to include patient preference information were identified.  Study II was an exploration of the patient perspective regarding the use of patient preference information in regulatory marketing authorisation decisions. Patients emphasised the need to have a say in decisions affecting their health and to be properly informed about potential risks and benefits of medical products.  Study III assessed patient preferences on benefits and risks of Rheumatoid Arthritis treatments. Results revealed that patients’ preferences differed substantially. The three most important treatment attributes for patients with rheumatoid arthritis were: the probability of severe side effects, treatment effectiveness and route of administration. Those placing relatively more importance on treatment effectiveness were willing to acceptance higher risk levels of side effects.  Study IV aimed to determine the influence of an educational tool, compared with traditional written information on patient preferences. It was found that those respondents receiving the educational tool focused more on the potential side effects than those receiving written information.  Patient preference information has the potential to reveal patients’ preferences on benefits and risks with scientific rigour and can therefore be weighed against clinical data. This thesis supports the development of a structured approach to learn about patient preferences on benefits and risks in medical approval

Getting a Say : Bringing patients’ views on benefit-risk into medical approvals

The focus of this thesis is a new quantitative approach to consider patient preferences on benefits and risks in medical approvals. The overall aim of this thesis was to explore how patient preference information may be relevant to regulatory marketing authorisation decisions. Study I provides an overview of the different decision-processes of industry, regulatory agencies and health technology assessment bodies/reimbursement agencies along the medical product lifecycle. In total, 15 decision points with the potential to include patient preference information were identified.  Study II was an exploration of the patient perspective regarding the use of patient preference information in regulatory marketing authorisation decisions. Patients emphasised the need to have a say in decisions affecting their health and to be properly informed about potential risks and benefits of medical products.  Study III assessed patient preferences on benefits and risks of Rheumatoid Arthritis treatments. Results revealed that patients’ preferences differed substantially. The three most important treatment attributes for patients with rheumatoid arthritis were: the probability of severe side effects, treatment effectiveness and route of administration. Those placing relatively more importance on treatment effectiveness were willing to acceptance higher risk levels of side effects.  Study IV aimed to determine the influence of an educational tool, compared with traditional written information on patient preferences. It was found that those respondents receiving the educational tool focused more on the potential side effects than those receiving written information.  Patient preference information has the potential to reveal patients’ preferences on benefits and risks with scientific rigour and can therefore be weighed against clinical data. This thesis supports the development of a structured approach to learn about patient preferences on benefits and risks in medical approval

Experiences of individuals with rheumatoid arthritis interacting with health care and the use of a digital self-care application: a qualitative interview study

Objectives Over the last few decades, there have been significant improvements in the treatment of rheumatoid arthritis (RA), with the development of new treatments and guidelines for teamwork and patient self-care and access to digital tools. This study aimed to explore the experiences of individuals with RA interacting with healthcare. It also looked at how a self-care application, an educational programme called the ‘healthcare encounter’, improved patient–doctor communication.Design Semistructured interviews were conducted, and qualitative content analysis was performed.Setting The potential participants, individuals with established, or under investigation for, RA diagnosis at rheumatology clinics in Sweden, were asked to participate in the study via a digital self-care application called the Elsa Science Self-care app.Participants Ten interviews were performed with participants from nine clinics following a meeting with the rheumatologist or other healthcare personnel between September 2022 and October 2022. Phrases, sentences or paragraphs referring to experiences from healthcare meetings and opinions about the digital programme were identified and coded. Codes that reflected similar concepts were grouped; subcategories were formulated, and categories were connected to their experiences and opinions.Results Among our participants, three main categories emerged: the availability of healthcare, individual efforts to have a healthier life and personal interaction with healthcare. Participants described that the ‘healthcare encounter’ educational programme can be a source of information, which confirms, supports and creates a sense of control.Conclusion The participants valued being seen and taking part in a dialogue when they had prepared themselves (observed symptoms over time and prepared questions). The implementation of digital self-care applications might need to be incorporated into the healthcare setting, so that both the patients and the healthcare personnel have a shared understanding. Collaboration is essential in this context

Would you consider donating your left-over embryos to treat Parkinson’s disease? Interviews with individuals that underwent IVF in Sweden

Background: Parkinson’s disease (PD) has been considered to be one of the most promising target diseases for forthcoming cell-based therapy. The aim of this study is to explore the views of individuals with cryopreserved embryos on using human embryonic stem cells for treating PD. Methods: The study was performed as a qualitative, semi-structured interview study in June–October 2020. Participants were recruited at a private fertility clinic located in one of the larger Swedish cities. The clinic provides both publicly financed and privately financed IVF-treatments. All interviews were performed by telephone and analyzed using thematic content analysis. Five main categories emerged from 27 sub-categories. Results: In total, 18 interviews were performed with 22 individuals, as either a couple (n = 16) or separately (n = 6). Participants had different views on what a cryopreserved embryo is. Some participants addressed cryopreserved embryos as ‘a lump of cells’, and some in terms of their ‘unborn child’. Conditions for donation of cryopreserved embryos for cell-based treatment in PD were: not losing control of what is happening to the embryo, that donating must be voluntary and based on informed consent with time for reflection, reimbursement, equality and transparency. Conclusions: Using cryopreserved embryos to treat PD is associated with fundamental ethical and practical issues. This study shows that IVF couples with left-over embryos may be supportive but there is a need for future research to assess people’s views on using cryopreserved embryos for cell-based treatment in PD on a more aggregated level

Functional capacity vs side effects: treatment attributes to consider when individualising treatment for patients with rheumatoid arthritis

Introduction: Individualisation of rheumatoid arthritis (RA) treatment needs to take account of individual patients’ preferences to increase patient-centeredness in treatment decisions. The aim of this study was to identify patient-relevant treatment attributes to consider when individualising treatment for patients with RA. Method: Patients with RA in Sweden were invited to rank the most important treatment attributes in an online survey (April to May 2020). Semi-structured interviews were conducted (October to November 2020) to further identify and frame potential attributes for shared decision-making. The interviews were audio-recorded, transcribed and analysed using thematic framework analysis. Patient research partners and rheumatologists supported the selection and framing of the treatment attributes across the assessment. Results: The highest ranked attributes (N = 184) were improved functional capacity, reduced inflammation, reduced pain and fatigue and the risk of getting a severe side effect. The framework analysis revealed two overarching themes for further exploration: treatment goals and side effects. ‘Treatment goals’ emerged from functional capacity, revealing two dimensions: physical functional capacity and psychosocial functional capacity. ‘Side effects’ revealed that mild and severe side effects were the most important to discuss in shared decision-making. Conclusions: Functional capacity (physical and psychosocial) and potential side effects (mild and severe) are important treatment attributes to consider when individualising RA treatment. Future research should assess how patients with RA weigh benefits and risks against each other, in order to increase patient-centeredness early on the treatment trajectory

Making space for patients’ preferences in precision medicine : a qualitative study exploring perspectives of patients with rheumatoid arthritis

Objective: Precision medicine in rheumatoid arthritis (RA) creates new opportunities to involve patients in early identification of accurate indicators of health trajectories. The aim of this study was to explore patient perspectives on patient-centredness in precision medicine for RA treatment. Design: Semistructured interviews were conducted to explore patients’ perspectives on a new personalised approach to RA treatment. The interview guide was developed together with patient research partners and health care professionals. Setting: An invitation to the interviews was sent through a mobile application. The interviews were one-on-one, using an interview guide with open-ended questions. Interviews were conducted digitally (October 2020–February 2021) via Zoom or telephone, depending on each participant’s preferences. Participants: Patients with RA (N=12) were purposively recruited. Patients were eligible if they had an RA diagnosis, were aged 18–80 years, and understood and expressed themselves in Swedish. Participants and researchers did not know each other prior to the interviews. Results: Participants expressed desires and needs for patients to have an active role in precision medicine by making shared treatment decisions together with a healthcare professional. In order for that to work, patients need information on potential treatment options, an ability to express their preferences, an individual treatment plan and identification of personal treatment goals. Patients also identified two requirements of healthcare professional in precision medicine: a safe environment to express personal matters and two-way communication with healthcare professionals. Conclusion: Communication between patients and healthcare professionals needs to be more focused on patients’ individual treatment preferences and expressed needs, in order to increase patient-centredness in treatment decisions, so shared decision-making can become a reality. More research is needed to design multifaceted implementation strategies to support patients and healthcare professionals to increase patient-centredness throughout treatment personalisation

Patient preferences on rheumatoid arthritis second-line treatment : a discrete choice experiment of Swedish patients

Background Preference assessments of patients with rheumatoid arthritis can support clinical therapeutic decisions for including biologic and targeted synthetic medicines to use. This study assesses patient preferences for attributes of second-line therapies and heterogeneity within these preferences to estimate the relative importance of treatment characteristics and to calculate the minimum benefit levels patients require to accept higher levels of side effects. Methods Between November 2018 to August 2019, patients with rheumatoid arthritis were recruited to a survey containing demographic and disease-related questions as well as a discrete choice experiment to measure their preferences for second-line therapies using biologics or Janus kinases inhibitors. Treatment characteristics included were route of administration, frequency of use, probability of mild short-term side effects, probability of side effects changing appearance, probability of psychological side effects, probability of severe side effects and effectiveness of treatment. Results A total of 358 patients were included in the analysis. A latent class analysis revealed three preference patterns: (1) treatment effectiveness as the single most important attribute, (2) route of administration as the most important attribute, closely followed by frequency of use and psychological side effects and (3) severe side effects as the most important attribute followed by psychological side effects. In addition, disease duration and mild side effects influenced the patients’ choices. Conclusion Respondents found either effectiveness, route of administration or severe side effects as the most important attribute. Patients noting effectiveness as most important were more willing than other patients to accept higher risks of side effects.IMI-PREFE