Dear Acting Commissioner Brenner:
On behalf of the Cystic Fibrosis Foundation, we write to provide comments in response to the Food and Drug Administration’s draft guidance on Pulse Oximeters for Medical Purposes — Non-Clinical and Clinical Performance Testing, Labeling, and Premarket Submission Recommendations.
Background on Cystic Fibrosis and Cystic Fibrosis Clinical Care
Cystic fibrosis is a rare genetic disease that affects nearly 40,000 adults and children in the United States. In people with CF, mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene result in a buildup of thick mucus in multiple organ systems, leading to lung damage, life-threatening infections, and other complications.
The CF Foundation is committed to ensuring that all people with CF have the opportunity to lead long, fulfilling lives. We achieve this by providing high-quality, specialized care through our national network of accredited CF care centers and supporting development of clinical care guidelines based on scientific research, medical evidence, and consultation with experts on best practices. These CF clinical care guidelines address a wide variety of topics — including advanced CF lung disease, for which pulse oximetry is critical in detecting hypoxemia and risk stratifying to appropriately time lung transplant referral. With this in mind, we offer the following considerations for the FDA as the agency refines its recommendations regarding nonclinical and clinical performance testing, labeling, and premarket submission for pulse oximeters for medical purposes.
Clinical Performance Studies and Skin Pigmentation:
We strongly commend the FDA for recognizing the body of scientific evidence indicating that the accuracy of pulse oximeters may be affected by skin pigmentation and drafting recommendations to address this serious issue. Use of medical devices with disparate performance between patients with varying levels of skin pigmentation undermines the ability of healthcare providers to adequately care for their patients and puts lives at risk. It may compromise medical decision-making with regard to the need for advanced medical therapies, lung transplantation referral, hospital admission, intensive care, and advanced respiratory support devices such as mechanical ventilation and extracorporeal membrane oxygenation. In addition, inaccurate pulse oximetry devices jeopardize access to medically necessary treatments following hospital discharge, such as home oxygen and other longer-term care. Because many pulse oximeters demonstrably overestimate oxygen saturation levels for patients with darker skin pigmentation, failure to ensure the accuracy of these devices through clinical performance studies disproportionately affects people of color, depriving some patients of appropriate medical care. In recommending clinical performance studies that enroll a balanced proportion of participants representing different skin pigmentation groups, as determined by both the Monk Skin Tone scale and Individual Typography Angle, the FDA is taking critical steps to help all patients by ensuring greater precision in medical-grade pulse oximeters and reducing the likelihood of dangerous underestimates of hypoxemia.
Labeling — Warnings and Statements Regarding Non-Disparate and Disparate Performance:
Healthcare providers must be able to fully understand the devices they are using in patient care, including the utility and limitations of those devices. Because of this, we strongly support comprehensive product labeling as proposed by the FDA, including a clear and prominent statement of non-disparate performance where applicable (e.g., “This pulse oximeter has been evaluated to perform comparably across groups of individuals with a wide variety of skin tones”, as per FDA recommendations).
We further encourage the agency to consider amending its product labeling guidance to recommend that sponsors include a clear and prominent statement noting that a device has not undergone sufficient testing to demonstrate non-disparate performance where applicable (e.g., “This pulse oximeter has not been evaluated for comparable performance across groups of individuals with a wide variety of skin tones”). Though the FDA recommends that labels include a broad warning stating that “differences in skin pigmentation may cause differences in pulse oximeter sensor performance and thereby impact SpO2 readings,” more specific information about individual products is likely to be of great use to healthcare providers.
Pulse Oximeters That Were Previously 510(k)-Cleared:
We agree with the FDA that it may be valuable for manufacturers of 510(k) cleared pulse oximeters to use real world data (RWD) to support the evaluation of non-disparate performance for those devices. Though the FDA has previously released recommendations regarding the Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices, we encourage the agency to consider providing further guidance on this specific issue.
Once again, the CF Foundation commends the FDA’s commitment to ensuring that pulse oximeters for medical purposes are safe and effective for every patient who relies on them for critical healthcare. We appreciate the opportunity to offer feedback on these recommendations and look forward to collaborating with the agency on this topic in the future.