How to Collect Patient-Reported Outcomes in Clinical Trials

Patient-reported outcomes (PROs) are an important way to include the patient voice in clinical trials. More than a quarter of clinical trials now use patient-reported outcomes, and with an increased focus on PROs from the FDA, that number is expected to grow in the coming years.

Patient-reported outcomes (PROs) are defined as "any report of the status of a patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else," according to the FDA.

PROs have become increasingly important to the FDA, in particular around label claims. In 2009, the FDA released guidelines stating that in order for label claims to be used in marketing, trials must collect PROs related to the patient experience.

The label claim guidelines aren't condition-specific, but the FDA has released additional guidance on using PROs for particular diseases. For example, in 2015, the FDA released draft guidance on non-small cell lung cancer calling for the need for PRO measures of tumor-related symptom benefit in future trials.

The bottom line is that PROs are important, and are only becoming more critical as the FDA continues to focus on patient centricity in clinical research. Ultimately, including PROs in your trial design should lead to a better therapy with meaningful benefit to patients. The timeline for including PROs can be long, however, so it's important to plan ahead and start engaging patients, PRO vendors, and even the FDA early on in the process.

How to collect PROs in a clinical trial

Step 1: Research existing PRO instruments for your condition area.

It can be helpful to start your research by performing a literature of review to get a sense of what PRO instruments have been used in the past, and whether those measures were used successfully in an FDA-approved label claim. You may find that there are existing PRO measures that suit your purposes, that you need to modify an existing PRO, or that you'll need to start from scratch for your particular use case.

Step 2: Conduct patient interviews or focus groups.

Particularly if you're modifying an existing PRO measure or creating a new one, an important next step is to talk with patients. Options include conducting patient interviews, running focus groups, or getting in touch with patient organizations. Patient input can help you determine what it's like to live with your trial's condition, and what quality of life improvements would be most meaningful for patients.

Step 3: Decide whether you'll use electronic patient-reported outcomes or paper forms.

As of 2014, around half of clinical trials that used PRO used electronic devices to capture data. While that number may seem low, use is expected to grow by 15% between now and 2025. While using electronic patient-reported outcomes (ePRO) involves up-front costs, advocates say that going digital helps reduce the time spent in data reconciliation. It also may provide more accurate data, as patients are more likely to record symptoms and answer questions in real time through an electronic device, studies suggest.

If you decide to use ePRO, talk with potential vendors to make sure their devices are compatible with your existing clinical trial technology.

Step 4: Formulate your questions and timing.

PROs are ideal for capturing data related to how a patient's quality of life has improved since beginning your treatment. They can also be used to measure adverse events in a clinical trial. And, PROs can be used to capture information about symptoms that aren't measured during clinical visits. It's particularly valuable to measure questions related to pain using PROs.

When creating patient-reported outcome questions, in addition to considering what information you would like to collect, it's also important to keep in mind how you're going to ask each question. Only 12% of Americans have proficient health literacy – many people struggle to understand the labels on medicine bottles, instructions from doctors, and other health materials. Use clear, unambiguous language when formulating questions. It's also a best practice to capture information about symptoms and adverse events, in particular, as quickly as they occur.

Experts also recommend keeping in mind the burden of questions on the patient. For example, consider limiting how many questions you ask patients to answer in a given sitting. Patients may also be more likely to answer questions more frequently if the question volume is limited.

Step 5: Conduct user acceptance testing.

Once you have your questions formulated and your PRO instrument, paper or electronic, ready, it's time to start user acceptance testing (UST). The ISPOR ePRO Systems Validation Good Research Practices Task Force put together a thorough guide to user acceptance testing to help. If you're working with an ePRO vendor, it's important to stay in close contact with them throughout this process in case tweaks need to be made to your e-diary or other tool based on user feedback.

Step 6: Submit your materials to your Institutional Review Board (IRB).

Throughout your PRO design process, it's important to consider your IRB. One of an IRB's main roles is to consider whether a trial impedes patient participation. In general, IRBs are more likely to look at the content of your PRO design, rather than whether you're using paper or an electronic device, but keep your patient population in mind when deciding to go digital or not. For example, there may be some cases in which an IRB determines that electronic devices aren't the right fit, such as for Alzheimer's patients.

Step 7: Train your site staff and develop a user guide.

No matter how intuitive your PRO instrument may be, chances are, patients and site administrators will have questions once your trial launches. Based on your findings from user acceptance testing, create a training guide for site staff that includes how to use the PRO instrument and answers to anticipated questions. Depending on the device being used, you may need to prepare your staff to answer questions about the user experience on several different devices.

Step 8: Start recruiting patients.

Once your materials have been approved and your sites have been selected, it's time to start enrolling patients in your trial. We created a clinical trial patient recruitment template to help. Download your free copy below, and let us know if Antidote can help you connect engaged patients with research.