s the end users of healthcare products, interventions, and related research, eliciting and incorporating patient preferences into clinical treatment and clinical trial design have become paramount in reconciling the different and often difficult trade-offs related to healthcare decision-making. Meaningful involvement of patients as active and equal research partners, through which they can formulate and express preferences resulting from their own cognition and experience, can be especially effective early in the healthcare product development lifecycle.

Because patient preference studies (PPS) elicit these patient views, the evidence they generate can help to fortify and inform stakeholders’ decision-making strategies throughout the therapeutic product development lifecycle and clinical treatment:

• Drug discovery and early development.
• Clinical development.
• Regulatory approval and marketing authorization decisions.
• Health technology assessment (HTA) and reimbursement decisions.
• Post-marketing (real-world treatment practices).

These qualitative and quantitative data simultaneously complement and enhance understanding of what matters most to patients, why it is important for them, and how much patients value these attributes.

In recent decades, researchers have developed different methods to find out the determinant factors in patients making decisions about not only participating in clinical trials but closely related decisions such as helping to identify pertinent clinical trial endpoints, contributing to regulatory benefit-risk or health technology assessments, and even decisions about their personal care. The following highlights of best practices and lessons learned in assessing and integrating patient preference into clinical treatment and clinical trial design also explain which attributes are important to patients and other unmet needs.

PPS yield evidence about the unmet needs, treatment outcomes, and other attributes (side effects, symptoms, efficacy outcomes, etc.) that are most important to patients, and the reasons why, plus how individual preferences differ according to patient characteristics (preference heterogeneity). Stakeholders across the medical product lifecycle (patients, patient organizations, pharmaceutical companies, regulatory authorities, HTA bodies, payers, and clinicians) agree that such evidence should be used to inform target treatment profiles and clinical/nonclinical endpoints in traditional and real-world clinical trials to help drug developers prioritize unmet needs and what truly matters to patients.

Preference studies also provide patients with systematic insight into their own needs and wants and allow patient organizations to advocate for what is important for patients based on their evidence. Nowadays, there is an increasing demand for preference data from patients and patient organizations, particularly in rare disease areas where it is unclear how much risk or uncertainty patients are willing to accept from their treatments and where little formal evidence exists on what patients want from their treatments.

Involving Patients and Patient Organizations in Preference Studies: Multiple Myeloma (MM)

The Myeloma PREFER case study highlighted that patients and patient organizations can provide valuable insights, including interpretation of the literature versus what happens in the real world. Patients have a well-positioned knowledge of the disease pathway and can help provide context on any access challenges and offer advice on how to interpret and use the study results in the real world. Involving patients and patient organizations in preference studies also helps to improve the quality of study protocols and patient materials.

Highlights identified in this case study include:

1. the importance of involving patients and patient organizations as study partners early in the lifecycle to include the patient perspective in all stages of preference study design, particularly in qualitative phases, and ensuring subsequent attributes make sense to them.
2. if possible, provide financial support and incentives for patient recruitment and consistent training for study staff.
3. patient organizations understand the increasing need to present evidence data to regulators and Health Technology Assessment (HTA) bodies to increase patient access.
4. most patient organizations do not have researchers within their organization and must partner with researchers who can help to build robust evidence based upon their understanding of patient and stakeholder needs.

MM PPS Survey Results

Because the rapid increase in potential new novel treatments for MM creates an urgent need to establish which treatment attributes matter most to patients, and which benefit-risk trade-offs patients may be willing to make, MM represents an important area where PPS provide valuable insights from the patient population.

One of the authors led a collaborative team to conduct a PPS to meet this end and evaluate methods to do so. A preference survey incorporating a discrete choice experiment (DCE) and swing weighting (SW) was completed by 393 disseminated patients with MM across 21 countries. This survey was developed based upon a qualitative study involving discussions with 24 patients with MM. Latent class and mixed logit models were used to determine the DCE attribute weights, and descriptive analyses were performed to derive SW weights. MM patients and patient organizations provided extensive feedback to researchers during the study design, development, and piloting.

The survey revealed that MM patients have:

1. the need for improvements in both life expectancy and symptoms, and reduction in side effects that substantially reduce their physical, mental, psychological, and social health (such as their mobility problems [bone fractures], thinking problems, reduced energy, pain, emotional problems, eating and digestive problems, and vision problems).
2. the psychological burden of dealing with uncertainties regarding long-term treatment outcomes, side effects, and symptom burden.
3. the need for more psychological, mental, and social support to help them cope with the psychological burden of dealing with uncertainties over long-term treatment outcomes, side effects, and symptom burden.

While life expectancy was most important to patients who had either a very small or a very large number of previous therapies, and quality-of-life-related attributes (e.g., pain and mobility problems) were most important to patients with a moderate number of previous therapies, the study revealed a significant preference heterogeneity depending upon participants’ previous experience of side effects and symptoms. Findings from this study also revealed large and significant preference heterogeneity, in individual attribute values and rankings, depending on participants’ prior therapy experience and experience of side effects and symptoms. On average, participants preferred the DCE questions over SW questions (42 percent vs 32 percent), but advantages of both methods were highlighted; participants preferring DCE found DCE simpler and quicker to complete, and participants preferring SW indicated they were more comfortable with their choices and highlighted the difficulty of trading off between life expectancy and quality of life, and between physical and mental health.

Patient Preferences and Enrollment Rates

Patient engagement in clinical study design improves enrollment rates. However, current efforts to engage patients tend to focus on small (and quite possibly not representative) samples of patients, generate qualitative instead of quantitative insights, and happen late in the study design process. Patients’ stated preference methods can potentially address these challenges by helping researchers understand how patient willingness to participate in clinical studies varies with study design and patient characteristics. A DCE was undertaken to measure how willingness to participate varies with the elements of study design, including but not limited to study location and duration; the amount of time required of patients; the types of data collected; the support provided to patients; and which patient characteristics are predictive of differences in willingness to participate. To understand patient diversity, the DCE was conducted with over 3000 patients from 10 countries and 8 therapy areas, and early analyses suggest that:

• About 45 percent of patients’ decisions to participate are influenced by study design.
• Patients vary in the elements of study design that influence their decisions.
• Choice models are able to predict observed rates of willingness to participate.
• Further work can usefully integrate insights from choice models into study design efforts.

Conclusions

Assessing and integrating patient preferences in study design provides a golden opportunity to simultaneously transform the patient experience of clinical research and care, decrease protocol design issues, and improve the evidence base upon which stakeholders make decisions, all to better meet patient needs. Collaboration is critical for patient preference studies designed to identify and elaborate on these needs. This includes the need for clinical research and care professionals to be trained and advocate for incorporating patient preferences as a crucial tool to inform the best treatment, design approaches, increase retention rates, and boost optimal use.

Evidence-driven preference studies represent progress to develop comprehensive insights into how patients make study participation decisions that might simultaneously boost patient satisfaction and enrollment rates. For example, the DCE can predict how participation rates vary with study and patient characteristics, and findings from PPS revealed that large and significant preference heterogeneity, in individual attribute values and rankings, depends on participants’ prior therapy experience and their experience of side effects and symptoms. These represent a significant opportunity to keep exploring and developing study designs to guarantee a tailored patient-centered experience while addressing challenges related to patient participation in studies.