Unmet needs: Patient-relevant clinical outcome assessments can provide strong evidence

Products addressing unmet needs often enjoy accelerated regulatory review and reimbursement. However, there is no consensus on how to define unmet needs among regulators, payers, health technology assessment (HTA) agencies, providers, and patients. Indeed, these players often have conflicting values, perceptions, and priorities. For example, payers in universal healthcare systems must deliver budget-conscious care to large populations, while private payers want to run profitable businesses. Meanwhile, patients will always seek the best treatment.

To identify an unmet medical need, sponsors must first understand a disease or condition and assess the current and future competitive landscape through literature searches, natural history studies, and consulting experts. But that won’t yield a complete picture. Patients are critical to identifying and quantifying unmet needs because they are the ultimate consumers of medicines and treatments. They are experts in their disease journey and know which outcomes matter to them. 

There is no single answer or definition of what is patient-relevant because what patients care about most is impacted by the stage of disease, line of treatment, available options, and personal preferences. And it’s not enough to interview patients and patient advocacy groups (PAGs) and hear what they want or need. The insights must translate into sound, measurable endpoints in a clinical trial design that collects enough data to prove safety and efficacy.

Gather evidence of unmet needs early

Clinical outcome assessments (COAs)—utilized and validated early in development and employed in pivotal studies—can demonstrate that a product meets an unmet need. For example, many people assume that cure or tumor shrinkage is the top priority for all cancer patients. Prevalent messaging speaks of “fighting” or “eliminating” cancer.¹  Yet some patients with advanced cancer may prefer a less effective drug with fewer side effects to the most up-to-date but very toxic treatment. In some indications, that could represent a meaningful, patient-relevant outcome and unmet need. 

COAs can't just be lifted from one condition to the next because patients with different conditions may have different concerns. A patient with an incurable disease and short life expectancy may value quality time free of symptoms and side effects more than a patient who could be cured by treatment.

There are four types of COAs

There is no single answer or definition of what is patient-relevant because what patients care about most is impacted by the stage of disease, line of treatment, available options, and personal preferences.

The FDA has prioritized patient-focused drug development (PFDD), issuing four guidance documents over the last four years.² Below is a COA roadmap we adapted from the agency’s PFDD guidelines.

Roadmap for selecting fit-for-purpose, patient-focused endpoints

COA instruments that are relevant to patients typically center around three factors that impact their quality of life while on a medication:

• Symptoms: Does the drug lessen the disease burden by eliminating or mitigating complications such as pain, fever, a lump or bump, or difficulty sleeping?
• Functions: Does the drug allow them to participate in activities of daily life when they otherwise could not?
• Intrusiveness of medication: Does the drug involve intrusive administration paraphernalia (bulky inhalers, injector pens, or hospital visits), monitoring procedures (lumbar punctures or serial blood tests), or side effects?

Sponsors often overlook intrusiveness when selecting COAs, but it is central to patients’ decision-making. Some sponsors are so focused on proving whether a drug works at the cellular level or is compliant with good manufacturing practices (GMP) that they forget how intrusive it may be in a patient’s everyday life. For example, inhaled insulin was hailed as a breakthrough for diabetes patients, and more convenient than subcutaneous insulin delivery. However, various side effects, medical insurance hurdles, and the fact that existing pen syringes and needles are almost painless for most diabetics, hampered uptake.³

Sponsors must balance time and cost when incorporating patient perspectives, but if they fail to submit adequate evidence of a drug’s impact on patient-relevant outcomes, their products could fail when challenged by regulators, HTA reviewers, and payers. 

To convince HTA agencies and payers, sponsors increasingly need to submit quality-of-life evidence to support pricing. Before they make an expensive new product available, they demand compelling data on patient benefits. It is important to carefully select COAs that—when measured adequately—reflect an aspect of health that is important to patients, can be modified by the investigational treatment, and could demonstrate clinically meaningful differences between study arms within the time frame of the planned clinical trial.

Ensure COAs are fit for purpose

At Parexel, we apply key performance indicators (KPIs) to new or existing COAs to determine if they are fit for purpose. Sometimes we find an existing COA that works or can be modified. Other times it is necessary to develop a wholly new COA or combine elements of existing ones into a new measure. When we determine that a COA is critically flawed, we move on and find better ones. 

Some COA instruments are flawed because they are difficult for patients to understand. For example, one commonly used PRO tool to measure patients’ “satisfaction” with a treatment begins with a convoluted question: “How satisfied or dissatisfied are you with the ability of the medication to prevent or treat your condition?” Patients are then supposed to rank their satisfaction on a scale of seven, from “Extremely Dissatisfied” to “Extremely Satisfied.” This is not intuitive and was not developed with patient input. An alternative PRO asks simpler questions such as “The side effects of the medicine interfere with my physical activity (e.g. lifting, walking, jogging, etc.).” Then patients can choose five answers from “Not at all” to “Very Much.” Patients contributed to the wording used in the second tool.

Key performance indicators (KPIs) can help companies select patient-relevant COAs

COAs allow sponsors to measure patient experiences and perceptions that have not been measured by traditional clinical research endpoints. Nothing could be more patient-centric than that. Developed, collected, and analyzed properly, COA data can support decisions made by regulators, HTA bodies, payers, providers, and patients.

Clinical outcome assessments allow sponsors to measure patient experiences and perceptions that have not been measured by traditional clinical research endpoints. Nothing could be more patient-centric than that.

Contributing Experts