Patient Perspectives on the Value of Patient Preference Information in Regulatory Decision Making: A Qualitative Study in Swedish Patients with Rheumatoid Arthritis

Traditionally, regulatory decision making has attempted to balance the risks and benefits of medical products according to the outcomes of clinical trials. However, as regulators have come to recognise that they may not assign the same value to risks and benefits as would patients, they have begun to emphasise patients’ perspectives [1]. Moreover, patients’ perspectives regarding risks, benefits, and treatment procedures vary [2, 3]. For example, not all patients would accept higher risks to gain a small benefit [4]. Patient perspectives are occasionally included in regulatory decision making via the inclusion of patient representatives in decision boards and groups in the EU [3]. Different instruments have also been developed to elicit and include patients’ experiences, such as patient-reported outcomes, which measure clinically meaningful endpoints. However, these methods cannot capture the relative importance of different clinical endpoints or how patients make trade-offs between risks and benefits [5].

The increasing interest in involving patients’ perspectives on risks and benefits has inspired the development of new methods that elicit and measure preferences in patient populations [1, 6]. To quantify the relative importance of medical product characteristics, methods such as discrete-choice experiments (DCEs) ask patients to choose treatment attributes [7]. In addition, patient perspectives can be assessed using patient preference information (PPI). According to the US FDA, PPI is “qualitative or quantitative assessments of the relative desirability or acceptability to patients of specified alternatives or choices among outcomes or other attributes that differ among alternative health interventions” [2]. PPI has been reported to support risk–benefit decisions by transparently framing issues from the patient’s perspective [8, 9] and by identifying subgroups when preferences differ [10].

In both the EU [1] and the USA [6], regulatory agencies have acknowledged a need for more research that investigates how patient preferences are assessed. Moreover, agencies have not established best practices (i.e., the PPI methods to use in regulatory decision making), when to use PPI, or how best to conduct patient-preference studies. Although regulatory agencies recognize the value of PPI, few studies have evaluated how patients view the use of PPI for regulatory decision making. Patients’ perspectives on PPI can provide input that can be used when recommending how to measure and implement PPI in regulatory decisions for drugs and devices in the medical product lifecycle (MPLC) [5, 9, 11].

This article focuses on the perspectives of patients with rheumatoid arthritis (RA) on the value of including PPI in regulatory decisions regarding (new) disease-modifying antirheumatic drugs (DMARDs). RA—a chronic inflammatory autoimmune disease—is characterised by tenderness, swelling, and destruction of joints, which can result in disability and premature death [12]. The individual burden includes decline in physical function, causing musculoskeletal deficits and reduced work capacity, resulting in high socioeconomic burden. Early treatment with DMARDs can control and prevent negative outcomes such as pain, stiffness, fatigue, fever, weakness, deformity, malaise, weight loss, and depression [13, 14]. Because patients with RA are familiar with the disease, treatments, and side effects, their experiences can contribute to understanding how best to use PPI in regulatory decision making. The aim of this study was to explore how patients with RA value the use of PPI in regulatory decision making regarding medical products.

A two-step approach was used to explore how patients with RA value the use of PPI in regulatory decision making for medical products. First, semi-structured interviews with regulators and patients were conducted to develop an interview guide. Second, focus groups were conducted with patients with RA in Stockholm and Uppsala, Sweden. The study was approved by the regional ethics review board in Uppsala, Sweden (Reg. no. 2017/001). All participants in the interviews and focus groups provided written informed consent.

The use of PPI in regulatory decision making regarding medical products has been emphasised in several initiatives to investigate methods that elicit patient preferences for regulatory decisions [1, 6]. This study brings a new aspect to this perspective by asking patients about their view on PPI in regulatory decision making.

The main finding in this study was that patients think PPI could provide valuable information for regulatory decision making. According to the participants, PPI could benefit both the patients and the regulators in that the regulators could take patients’ needs, lifestyles, and well-being into consideration when evaluating and approving (including post-approval) medical products. Both stakeholders could also benefit from PPI through the ability to identify and value important treatment characteristics for patients, as regulators may not be adequately informed about patient perspectives when only referring to the results of clinical trials. For example, PPI can provide information about the relative importance of different medical product characteristics. This finding is consistent with previous findings that PPI is important to consider in regulatory decisions [10, 17].

The participants also discussed possible limitations with PPI, such as an inability to capture how patients differ in their preferences because the preferences of patients with RA do vary [18]. However, preference studies can make it possible to present how preferences differ within subgroups of the patient population. Methods that elicit patient preferences, such as DCEs, can also quantify the relative importance of risks and benefits of medical products and make the information valuable for regulatory decisions [10].

In addition, participants expressed that PPI should be used to complement information from clinical trials. This finding is in line with those of previous research, that regulators should consider how patients weigh risks and benefits when making regulatory decisions [1]. Participants also recognise that the risk and benefit evaluation is an important step in the MPLC for implementing the use of PPI. Patients may adopt this reasoning because they do not want market approval for medical products that could expose them to a certain side effect [4].

Some participants expressed concern about pharmaceutical companies conducting patient-preference studies, with some thinking pharmaceutical companies should not be involved in conducting preference studies. One reason for expressing this concern might be a worry that pharmaceutical companies introduce bias to PPI. Other participants thought it would be good for pharmaceutical companies to have the information early in the product-development process.

A third finding was the identified need to inform participants in preference studies about the use of the study, the disease, and the medical product’s characteristics. Participants may have expressed a need for information because it was important to them that patient preferences used in regulatory decision making are representative and well-informed. This need for information may also relate to their desire that participants in preference studies represent a range of experiences with the disease and its treatments. However, adequately informing patients about the medical product characteristics included in the preference study might decrease this concern by increasing the participants’ ability to make a well-informed choice when answering the questions.

This study has several limitations. Patients in the focus groups were approached by their patient organisation, which could influence their perspective toward including PPI in regulatory decision making. Another possible limitation is selection bias, since the patient sample mostly consisted of highly educated females aged > 50 years. Although this was partly expected because the prevalence of RA increases with age and is about twice as high in women as in men [19], it might have slightly influenced study outcomes.

Patients think it is important to be involved in regulatory decisions regarding medical products and believe that PPI could be a valuable tool for assessing the preferences of patients. When answering a preference study, it is essential that patients are well-informed about the use of preference data, the disease, and the medical product characteristics. Further research that focuses on methods for informing participants in a preference-elicitation study is needed to increase the value of PPI in regulatory decision making.