How to Implement Patient-Centered COAs

By Alycia Shilton-Lloyd, Ph.D., Imago BioSciences

Drug developers often talk about “patient-centric,” but most find it difficult to prioritize a patient-centric approach to research in the early stages of drug development. While the majority of development teams understand that a patient’s experience living with a disease should inform treatment decisions, it has been difficult to hear directly from patients and incorporate their feedback into trial design early on. departure.

Drug approvals are based on validated measures of safety and efficacy. An effective drug is one that slows, stops, or even reverses clear clinical markers of disease activity. Assessments that clinicians use to judge disease activity or progression, such as cardiac ejection fraction or the size of lesions on an image, are obvious measures of disease activity used to assess the effectiveness of a treatment. But many disease activity assessments are used because they are easy to measure, convenient, inexpensive, or noninvasive. These measurements may not read disease activity directly, but are accepted substitutes. In addition, the vast majority of these evaluations provide objective figures. These measures have always been favored over subjective measures of the patient’s experience with the disease.

Biomarkers can reflect disease activity, but often do not reflect patient experience – this is especially true for palliative treatments. For example, in patients with myelofibrosis, reduction in spleen volume was presumed to be an indirect indicator of symptom improvement. An enlarged spleen, however, is not the cause of most reported symptoms; indeed, neither spleen size nor reduction in spleen size is associated with overall outcomes. It is certainly not useful as a sole measure of the impact of treatment on the patient experience.

This slow but steady evolution towards a reflection on the “effective” management of the disease from the point of view of the person living with the disease has led to the creation and adoption of tools designed to measure the impact of a medicine on a patient’s life due to a new treatment regimen. . This is best implemented by evaluating clinical outcomes. Clinical Outcome Assessments (COAs) are questionnaires or diaries that capture how a patient feels and functions. These patient reported outcomes (PRO) can extend to the patient observer/caregiver (ObsRO) or a clinician (ClinRO). Innovative drug developers strive to incorporate COAs that measure the most significant changes in how a patient feels and functions into their clinical trials. But it has been difficult to generate validated tools that reliably measure what matters most to patients. This has led to numerous PRO assessments, and versions of these PROs, for the same disease state. Licensing and implementing the right PRO is complicated and expensive.

Regulatory guidance

Regulatory authorities are placing greater emphasis on patient experience, both in trial design and drug labeling. The use of a patient-centered drug development approach has advanced significantly with the help of the FDA. The FDA, along with contributions from private and academic groups, has issued guidelines detailing how researchers can collect and submit COAs and other relevant information from patients and caregivers in a manner consistent with the agency regulatory decision. This four-part guidance series aims to facilitate the advancement of patient-oriented drug development and has involved the generation of numerous assessment tools designed to measure clinically meaningful changes in all aspects of patient well-being. during treatment. The first guidance document was finalized and published by the FDA in 2020, and the second document followed earlier this year. The agency is currently developing the third guidance document entitled Selection, development or modification of fit-for-purpose clinical outcome assessments. You can view the draft guidelines here. These guidance documents are important as more of the patient experience becomes part of the endpoint of clinical trials. A common theme running through workshops and presentation projects in the forthcoming third FDA guidance document is the importance of engaging with the FDA and implementing patient-centered research practices as soon as possible. possible in the clinical study process.

Seeking patient perspectives

As indicated in the guidance documents, the patient’s point of view should be sought. The patient is best placed to report their personal experience of living with a specific disease or condition. Observers will invariably fail to grasp the magnitude and severity of the signs, symptoms, and other challenges that impact a patient’s life. A preponderance of studies have shown that clinicians underreport both the number and severity of symptoms a patient experiences and often prioritize their management differently than a patient would. For many conditions and conditions, the treatment priorities most important to the patient have been documented in a Patient’s Voice report. These reports are the results of FDA-led patient-oriented drug development (PFDD) meetings, externally-led PFDD meetings, or patient listening sessions for the disease or condition in question. All existing reports can be found on the FDA CDER condition-specific meeting reports page.

A major challenge for drug developers is to seek patient feedback early enough in the COA selection process so that the COA tools used capture the outcomes that matter most to the patient. It can be difficult to ask patients for assurance that the COAs you have selected are measuring the most important outcomes once you are far down the development pipeline – when the machinery of a robust protocol and clinical operation is well established. Using an existing Voice of the Patient report at the earliest stage of clinical development can help ensure that you are on the right track to selecting meaningful COAs. If a PFDD meeting or patient listening session has not yet taken place for the disease or condition in question, it will be essential to partner with patient advocacy groups to obtain this information as soon as possible. . A patient-centered approach includes both an ongoing dialogue with patients and an ongoing search for the best ACOs for a particular upcoming trial.

We have reached a tipping point as an industry. We have access to patient information and more and more validated tools are being developed to measure this information and decipher how well our medicines meet patients’ expectations for managing their disease. As part of this tipping point, we are seeing COAs increasingly appear in protocols as co-primary or secondary endpoints with positive results as claims on labels. PROs now play a key role in drug approvals in therapeutic areas as diverse as oncology, gastroenterology and neurology. The importance of PROs in regulatory decision-making is crucial to allow the impact of a new drug on the patient to be part of the prescribing information and valuable story. This alerts the healthcare provider to this impact, making it easier to align the physician’s treatment goals with those of the patient.

Tips for Implementing PFDD

I believe the best way to advocate for patient-centered drug development is to make it easy for others to follow suit. Here are six ways your organization can implement patient-centered drug development practices and begin incorporating COAs into your own trial protocols:

  1. Focus on treatments that can actually improve patients’ lives. This is an ambitious and challenging goal, but consider developing treatments that hold the prospect of providing significant clinical benefit. The goal should always be to develop medicines that leave a significant and lasting impact on patients. While gradual improvement is good, there are more than enough conditions that desperately need better treatments.
  2. Listen to the daily experiences of your patients. Patients know what it is like to live with their condition and what they would consider a clinical benefit. Understand their experiences and use clinical development tools that measure major issues affecting patients.
  3. Patients who feel better take their medication. Compliance with clinical trials is a major factor in determining efficacy. It is also a major determinant of drug use in the real world. By documenting improvement in the subjective aspects of a trial outcome that reflect patients’ opinions, adherence and uptake of treatment will be improved. You can’t claim what you don’t measure.
  4. Be open to sharing your ideas. Patient-centered drug development is constantly evolving, and sharing what we learn from payers, the FDA, healthcare providers, and patients will accelerate that evolution.
  5. Experiment with different tools. There are many tools that one can use. It’s not always obvious which ones to use for a given treatment, specific patient population, or specific trial design. Input from the FDA and other groups dedicated to advancing patient-oriented drug development is readily available.
  6. Make your clinical progress accessible to the patients you serve. Part of our practice at Imago BioSciences is to make our clinical trial results in plain language for the benefit of interested patients. This invites patients into the drug development process and provides Imago with an additional opportunity for feedback.

By identifying and leveraging patient-reported COAs in trial designs as endpoints, life science companies can better develop effective drugs that are really centered on the patient before being launched. A good place to start is to collectively measure what matters most to patients – and COAs help us get there.

About the Author:

Alycia Shilton-Lloyd, Ph.D., is Vice President of Medical Affairs at Imago BioSciences, a clinical-stage biopharmaceutical company that discovers and develops new drugs for the treatment of myeloproliferative neoplasms (MPNs) and other diseases of the bone marrow. Alycia leads the company’s patient engagement activities for bomedemstat, their novel LSD1 inhibitor.