Patient-reported Outcomes Require Validation


February 3, 2022

In late January 2022, the FDA issued a guidance for the use of patient-reported outcomes (PROs) to be used across the total product life cycle (TPLC). Device makers should be aware that a PRO may be recommended by the FDA in some instances, but these measures must be validated by the sponsor before they can be used in regulatory decision-making.

The guidance addresses the principles for selecting and developing PROs for studies and trials regulated by the FDA’s Center for Devices and Radiological Health (CDRH) and the Center for Biologics Evaluation and Research (CBER). The information gathered by PROs is to be treated as valid scientific evidence for the purposes of regulatory decision making, and this guidance is exclusive of a patient-focused drug development guidance used by CBER and the FDA’s Center for Drug Evaluation and Research (CDER).

The guidance states that the use of a PRO in a clinical trial is voluntary, but that the use of a PRO may be recommended in certain standards and guidances. Given that a PRO is to be used across the TPLC, manufacturers may find the FDA recommends their use in post-approval studies and post-market surveillance studies. However, the guidance makes clear that developing a PRO in some instances will require considerable up-front work by the manufacturer before the results can be used in regulatory decisions.

There are several considerations in determining whether a given PRO is fit for the purpose for which the manufacturer intends to apply it. The first and primary consideration is whether patients find the concept behind the PRO to be meaningful and whether a change to that concept of interest (COI) would also be meaningful. The manufacturer must also provide evidence to the FDA that the PRO actually measures the COI.

The guidance states that a key consideration in assessing whether a PRO is appropriate for a given use is whether that PRO was developed in an appropriate context of use (COU). The PRO should be validated in the context of a patient population that is similar to the population that will enroll in the clinical trial in which the PRO will be deployed. This could hinge on questions such as whether the population in which the PRO was validated was at a similar disease stage as the population that will enroll in the clinical study.

Guidance for Patient Input into Clinical Trials Available

The FDA also released a guidance in January 2022 for patient engagement in the design and conduct of clinical studies. This guidance was developed with the input of a two-day meeting of the FDA Patient Engagement Advisory Committee (PEAC) in 2017, but only patient advisors would be eligible to provide input into the design and conduct of a clinical trial.

The guidance defines a patient advisor as someone who has had experience living with a disease or condition, but who will not enroll in the study in question. However, the advisor may have taken part in a previous study of that disease or condition, although it may be difficult to identify a potential advisor for rare diseases.

Among the benefits of using a patient advisor in the design of a study are improved enrollment and lower rate of loss of follow-up, although an advisor can be helpful in assisting the sponsor improve the performance of an ongoing study as well. The use of a patient advisor falls outside the purview of an institutional review board (IRB), although the FDA said in the guidance that other legal considerations are outside the scope of the guidance.

One of the limitations of this guidance is that CDER does not recognize the policy, which was authored by CBER and CDRH. The FDA did not address the applicability of the guidance to combination products that include a drug component regulated by CDER, although the text of the guidance does not rule out the possibility that a device-led combination product with a CDER-regulated drug component does fall within the scope.

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