Moving COAs Beyond the Regulatory Silo

Patient-centered outcomes in the pharmaceutical industry often exist within an organizational silo focused on supporting regulatory approval through clinical outcomes assessments (COAs). Sometimes the work of COA researchers overlaps with other disciplines, such as health economics, where utility or conjoint analyses are performed, or with real-world evidence teams when patient narratives are used to contextualize findings from database studies.

However, COA research has concentrated on ensuring the patient voice is included in drug development and when measuring what matters to patients. This traditional focus is broadening, with growing interest in using patient-centered information beyond the regulatory framework to help secure reimbursement, support product adoption, inform commercial strategy, and advise clinical operations on future trial designs.

Compared with earlier decades, when trial designs were built primarily on the perspectives of clinical experts, patients are now directly contributing to the process. They help define disease burden, identify barriers to trial participation, and assess whether observed changes in trials represent meaningful improvements in health status and health-related quality of life (HRQoL). Some protocols now explicitly document how patients have contributed to trial designs and reviews.

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The question is whether the information COA researchers obtain is being fully leveraged. There is a compelling case that more can be done to maximize the value of patient-based data.

Integrated Evidence Generation Planning

An integrated evidence generation plan (IEGP) is a strategic roadmap for producing scientifically sound evidence that meets the needs of all relevant stakeholders, including clinical, regulatory, medical affairs, and commercial teams, as well as the decision-making audiences they serve, such as clinicians, regulators, and reimbursement bodies.

Effective IEGPs start early in the product life cycle, sometimes preclinically but certainly by Phase 1, and continue through postlaunch. The aim is to ensure that all relevant information for all intended uses is collected at the right time, using rigorous methods, so it is available when each audience needs it.

‘There is a compelling case that more can be done to maximize the value of patient-based data’

Success in IEGP is not achieved by each function working separately and hoping their outputs align. It comes from thoughtful integration across workstreams, supported by ongoing debate, education, prioritization, and adjustment, over many years.

The COA Researcher’s Role in an IEGP

COA researchers must be aware of the needs of all relevant stakeholders to ensure that recommendations on patient-centric trial endpoints address more than just regulatory requirements. These include the needs of health technology assessment (HTA) agencies, prescribers, payers, patients, and, in some cases, caregivers.

‘Success in IEGP is not achieved by each function working separately and hoping their outputs align‘

Measure selection often focuses on expert opinion and precedent, but evidence should also guide decisions. Many COA researchers have seen measures chosen on the recommendation of respected academics or key opinion leaders that, while well intentioned, could never meet current regulatory standards for substantiating treatment benefit claims. Some COAs are selected purely based on precedent for reimbursement, even if the COA is not disease specific. Evidence demonstrates that the measure has been developed with strong patient-focused principles as the critical factor.

It is important to avoid simply replicating the protocol of another company working in the same therapeutic area. If the original strategy was not evidence based, following it could lead to the same shortcomings. Collecting and sharing evidence across stakeholders helps ensure programs are built on data rather than precedent.

COA researchers also function as cultural liaisons. Endpoint positioning may need to reflect the fact that some reimbursement authorities prioritize certain aspects of a disease over others. Cultural differences can also influence reporting patterns, such as underreporting pain in some Eastern cultures compared with Western contexts. These differences can affect protocol design and the likelihood of achieving a successful global product launch.

Anticipating Evidence Needs for Global Success

Some HTA bodies in Europe require analyses based on quality adjusted life years (QALYs), which has led to widespread inclusion of the EQ-5D in trial protocols. The EQ-5D measures only five domains of HRQoL, which may be insufficient for many diseases and especially for rare conditions with heterogeneous presentations, such as neurodevelopmental disorders in children.

An IEGP anticipates such limitations and prompts COA researchers to work with health economics and HTA colleagues to ensure appropriate measures are used. This might involve linking a disease-specific HRQoL assessment to a utility measure, if the HTA accepts that approach, or explaining why additional HRQoL assessments should be used alongside utility measures in reimbursement decisions.

Leveraging Existing COA Activities

Much of the evidence COA researchers generate can be repurposed to meet broader strategic needs. Three common opportunities are:

‘Measure selection often focuses on expert opinion and precedent, but evidence should also guide decisions’

Patient burden
Establishing the disease burden is often central to launch and regulatory strategy. In rare diseases, where stakeholders may have no prior experience with the condition, educating clinicians, regulators, and other decision-makers is essential. Qualitative interviews conducted during instrument development in early phase trials can yield data that are reasonably generalizable and can form the basis for survey research and real-world strategies.
Screening and identification
Identifying the right patients for clinical trials is critical to advancing development and demonstrating maximum treatment effect. Postlaunch, some companies create “ask your doctor” tools to help patients recognize their condition and seek treatment. Qualitative research from instrument development can be adapted to identify the key complaints that drive health care–seeking behavior.
Commercialization
In the United States, direct-to-consumer marketing can incorporate patient quotes and experiences. These often originate from early qualitative research, making it important to collaborate with commercial colleagues to ensure that any use of patient narratives aligns with FDA guidance and communication regulations.

New Areas of Inquiry for COA Researchers

The IEGP process can identify the benefits of COA research that may extend beyond traditional symptom and impact assessments. Areas of opportunity include:

  • Tolerability, which can be a competitive advantage if it is favorable compared with existing treatments, or if side effects are not disruptive to daily function.
  • Embedded interviews, now used in Phases 1, 2, and 3, to capture the burden and diagnostic journey at baseline, treatment expectations and tolerability, meaningful change, and to assess when patients notice changes in their health status.
  • Personalized endpoints, where patients select measures to assess treatment benefit, as encouraged by FDA guidance.
  • Digital endpoints, using wearable or app-based tools to collect sensor-generated measures, such as step count or sleep quality.
  • Caregiver and family impact, which is increasingly requested by some HTAs in pediatric rare disease contexts.
  • Clinician and caregiver measures of severity and impact, which are particularly important when patients are poor reporters or unable to self-report.

Identifying these approaches to evidence generation early in the planning phase allows consideration of endpoints that may become more widely adopted in the future.

The Cross-Functional Imperative

The COA researcher’s role in integrated evidence planning is essential, not only for regulatory success but also for favorable reimbursement decisions and commercial viability. Shared goals, cocreated solutions, and intelligent reuse of existing data are central to developing effective IEGPs.

The evidence generated by COA researchers is a critical element required for optimal evidence generation planning across all stakeholders. By integrating patient-centered evidence across regulatory, reimbursement, and commercial domains, COA researchers ensure that the patient voice informs decision-making at every stage of development and launch.

‘The COA researcher’s role in integrated evidence planning is essential’