Development of a Patient-Reported Outcome Measure to Assess Symptoms Associated with Cataract Surgery and Intraocular Lens Implants.

PURPOSE: To develop a standardized patient-reported outcome measure of visual perceptions and symptoms for implanted premium and monofocal intraocular lenses (IOLs). DESIGN: Observational study before and after IOL implants to assess the measure and symptom experience. PARTICIPANTS: Adults scheduled for binocular implantation of the same IOL type completed the survey at baseline prior to surgery (n = 716) and postoperatively (n = 554). Most respondents were female (64%), White (81%), 61 or older (89%), and had some college or more education (62%). METHODS: Administration was by web survey with mail follow-up and phone reminders. MAIN OUTCOME MEASURES: Frequency, severity, and level of symptom bother in the last 7 days for 14 symptoms: (1) glare, (2) hazy vision, (3) blurry vision, (4) starbursts, (5) halos, (6) snowballs, (7) floaters, (8) double images, (9) rings and spider webs, (10) distortion, (11) light flashes with eyes closed, (12) light flashes with eyes open, (13) shimmering images, and (14) dark shadows. RESULTS: The median correlation among having 14 symptoms at baseline was only 0.19. Mean uncorrected binocular visual acuity improved from a preoperative value of 0.47 logarithm of the minimum angle of resolution (logMAR; Snellen 20/59) to a postoperative value of 0.12 (20/26) and best-corrected binocular visual acuity improved from 0.23 logMAR (20/34) preoperative to 0.05 logMAR (20/22) postoperative. The most bothersome symptoms were reduced after surgery: preoperative/postoperative glare (84%/36%), blurry vision (68%/22%), starbursts (66%/28%), hazy vision (63%/18%), snowballs (55%/17%), and halos (52%/22%). All symptoms decreased significantly (P < 0.0001) from before to after surgery except for dark crescent-shaped shadows (4%/4%). The percentage of symptoms rated as quite a bit or extremely bothersome declined from before to after surgery except for dark crescent-shaped shadows (29%/32%): blurry vision (54%/15%), snowballs (52%/14%), glare (49%/15%), and halos (46%/14%). Having monofocal IOL implants was associated with significantly more reduction in halos, starbursts, glare, and rings and spider webs, but less improvement in self-reported general vision. CONCLUSIONS: This study provides support for the 37-item Assessment of IntraOcular Lens Implant Symptoms (AIOLIS) instrument for use to assess symptoms and general perceptions of vision in clinical studies and clinical care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Symptoms and Satisfaction Levels Associated with Intraocular Lens Implants in the Monofocal and Premium IOL Patient-Reported Outcome Measure Study.

PURPOSE: To develop a questionnaire with standardized questions and images about visual symptoms and satisfaction administered before and after cataract surgery with monofocal and various (premium) intraocular lenses (IOLs). DESIGN: A prospective, observational study of cataract surgery patients completing a self-administered questionnaire preoperatively and postoperatively at 4 to 6 months. PARTICIPANTS: Five hundred fifty-four patients with plans to undergo implantation of the same IOL in both eyes on separate occasions in 20 ophthalmology practices. METHODS: An 86-item questionnaire with standardized images assessed the following 14 symptoms: glare, blurry vision, starbursts, hazy vision, snowballs, halos, floaters, double images, rings and spider webs, light flashes with eyes closed, distortion, light flashes with eyes open, shimmering images, and dark crescent-shaped shadows. MAIN OUTCOME MEASURES: Symptom severity and level of symptom bother, satisfaction with vision, quality of vision, and ability to see without corrective lenses or eyeglasses. RESULTS: Except for dark crescent-shaped shadows, the report of visual symptoms significantly decreased postoperatively. Best uncorrected binocular visual acuity improved from 0.47 (20/59 Snellen visual acuity values) ± 0.35 logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.12 (20/26 Snellen visual acuity values) ± 0.12 logMAR postoperatively. Patients' ratings of intermediate vision as good to excellent improved significantly from 12% preoperatively to 71% postoperatively, and patients' ratings of distance vision improved from 8% preoperatively to 85% postoperatively. After surgery, 84% reported that they were somewhat, very, or completely satisfied with their vision. Most patients (88%) reported that they could see pretty well, very well, or perfectly well without corrective lenses after surgery. CONCLUSIONS: The Assessment of IntraOcular Lens Implant Symptoms questionnaire can be used across a wide variety of IOLs to evaluate visual symptoms and satisfaction with a growing segment of the market, premium IOLs, that target intermediate and near vision, in addition to distance vision. Compared to patients receiving monofocal IOLs, patients receiving premium IOLs appear to be more challenging to satisfy because of their requirements for distance, intermediate, and near vision, and their desire to be free of eyeglasses postoperatively. This instrument provides a structured, uniform tool for regulators, researchers, and ophthalmologists in everyday practice to gain insights into patients' experiences. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Do PRO Measures Function the Same Way for all Individuals With Heart Failure?

Women diagnosed with heart failure report worse quality of life than men on patient-reported outcome (PRO) measures. An inherent assumption of PRO measures in heart failure is that women and men interpret questions about quality of life the same way. If this is not the case, the risk then becomes that the PRO scores cannot be used for valid comparison or to combine outcomes by subgroups of the population. Inability to compare subgroups validly is a broad issue and has implications for clinical trials, and it also has specific and important implications for identifying and beginning to address health inequities. We describe this threat to validity (the psychometric term is differential item functioning), why it is so important in heart-failure outcomes, the research that has been conducted thus far in this area, the gaps that remain, and what we can do to avoid this threat to validity. PROs bring unique information to clinical decision making, and the validity of PRO measures is key to interpreting differences in heart failure outcomes.

Investigating gender-based differential item functioning on the Kansas City Cardiomyopathy Questionnaire (KCCQ) using qualitative content analysis.

PURPOSE: The purpose of this study is to evaluate potential gender-based differences in interpreting the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and to explore if there are aspects of health-related quality of life (HRQOL) not captured by the KCCQ-23 that are important to assess in men and/or women with heart failure (HF). METHODS: Patients ≥ 22 years of age with clinician-diagnosed HF and left ventricular ejection fraction ≤ 40% were recruited from two academic medical centers to participate in semi-structured concept elicitation and cognitive debriefing interviews. Enrollment was stratified by patient-identified gender (half women/half men). All interviews were conducted over the phone/web and audio recorded. Interviews were transcribed and descriptive qualitative content analysis was used to summarize findings overall and by gender. RESULTS: Twenty-five adults (56% women) diagnosed with HF participated. The average age was 67 years (range: 25-88). Women attributed a wider variety of symptoms to HF than men. Some participants had difficulty differentiating whether their experiences were due to HF, side effects of their medications, or age. We found very little evidence that participants interpreted KCCQ-23 items differently based on gender. CONCLUSIONS: Overall, our findings indicate that interpretation of the KCCQ-23 items were similar in men and women. However, some modifications to items may improve clarity of interpretation for a wide range of patients.

Measuring Patient Preferences at the FDA Center for Devices and Radiological Health: Reflections and Projections.

OBJECTIVES: Patient preference information (PPI) is a way to incorporate the patient voice in the evaluation of medical devices. The US Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) has been working to encourage the voluntary inclusion of PPI throughout the medical device lifecycle for nearly a decade. This article reflects CDRH's efforts to encourage collection of PPI and offers perspectives on the future of PPI in the evaluation of medical devices. METHODS: CDRH regulatory guidance, public meetings, and collaborations relating to PPI were explored. RESULTS: Since 2012 when CDRH issued guidance on how PPI can be used as scientific evidence in the benefit-risk regulatory submission, CDRH has issued 5 subsequent guidance documents expanding on the use of PPI in medical device evaluations. CDRH remains committed to advancing the science and application of PPI in the medical device ecosystem through many collaborations with professional organizations, patient advocacy groups, and academic institutions. By hosting and actively participating in multiple scientific and regulatory public meetings and conferences, CDRH fosters a continuous learning environment where the experience of using PPI in regulatory submissions can be shared. A September 2020 meeting cosponsored by FDA and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) discussed the state of PPI in regulatory applications and beyond. CONCLUSION: This article describes these pivotal events that have helped to increase the use of PPI in medical device evaluation as well as discusses future applications of PPI.

Integrating the Voice of the Patient Into the Medical Device Regulatory Process Using Patient Preference Information.

The US Food and Drug Administration is one of several US and global agencies making strides to incorporate patient preference information (PPI) into its decision making. PPI has been included in 5 completed medical device marketing decisions to date. Its usage is not more widespread because of uncertainty about how to design "fit-for-purpose" patient preference studies and a lack of standards for the choice of preference elicitation methods, among other reasons. To advance the application of PPI to decision making about medical devices, the Food and Drug Administration has published a guidance document, "Patient Preference Information-Voluntary Submission, Review in Premarket Approval Applications, Humanitarian Device Exemption Applications, and De Novo Requests, and Inclusion in Decision Summaries and Device Labeling." This article discusses key concepts in the guidance document, in addition to providing lessons learned from the use of PPI for medical device regulatory applications to date and identifying new opportunities to leverage PPI to elevate the patient voice in the medical device product life cycle.

Assessment of Clinical Trials for Devices Intended to Control Myopia Progression in Children.

The increased prevalence of myopia in the United States and other regions of the world, and the sight-threatening problems associated with higher levels of myopia have led to great interest in research designed to reduce these rates. As most of the progression of myopia occurs in childhood, these investigations have been directed toward slowing the progression of myopia in children. Treatments described to potentially slow the progression of myopia have included pharmacological interventions, multifocal spectacles, and multifocal correction created by contact lenses. Although some contact lens clinical trials have demonstrated promising results in slowing the progression of myopia, many of these studies have significant limitations, including only short follow-up times, limited randomization, and incomplete masking. Such limitations have underscored the need to develop a more robust clinical study design, so that future studies can demonstrate whether contact lenses, as well as other medical devices, can be used in a safe and effective manner to control myopia progression. We review previous key studies and discuss study design and regulatory issues relevant to future clinical trials.

Acanthamoeba: An Overview of the Challenges to the Development of a Consensus Methodology of Disinfection Efficacy Testing for Contact Lens Care Products.

With the increasing incidence of more pathogens that can cause microbial keratitis (MK), it is necessary to periodically reassess disinfection multipurpose solutions testing requirements to ensure that relevant organisms to challenge them are being used. Current testing protocols have included common pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, Serratia marcescens, Candida albicans, and Fusarium solani but have omitted less common pathogens such as Acanthamoeba. Specifically, Acanthamoeba sp. has recently been identified as a prevalent cause of MK in certain countries. Developing an appropriate protocol for this unique organism presents a challenge, given its two distinct life stages, methods to grow the organism, encystment techniques, and many other parameters that can affect testing outcomes. Therefore, the appropriate combination of these parameters is crucial to developing a protocol that ensures consistent, accurate results. The FDA has recognized the importance of establishing a standardized testing protocol for this pathogen and embarked on research efforts to provide a recommended testing protocol for testing contact lens care products.

Food and Drug Administration, American Academy of Ophthalmology, American Academy of Optometry, American Association for Pediatric Ophthalmology and Strabismus, American Optometric Association, American Society of Cataract and Refractive Surgery, and Contact Lens Association of Ophthalmologists Co-Sponsored Workshop: Controlling the Progression of Myopia: Contact Lenses and Future Medical Devices.

The prevalence of myopia is high and increasing. Approximately 5 billion people around the world are expected to be myopic by the year 2050. Methods to slow the progression of myopia and therefore potentially decrease the associated sight-threatening complications have been the subject of a number of investigations. A workshop, sponsored by the United States Food and Drug Administration (FDA) Center for Devices and Radiological Health, American Academy of Ophthalmology, American Academy of Optometry, American Association for Pediatric Ophthalmology and Strabismus, American Optometric Association, American Society of Cataract and Refractive Surgery, and Contact Lens Association of Ophthalmologists, Inc, convened myopia experts from around the world to discuss principles to consider in the design of clinical trials investigating the effectiveness and safety of myopia control devices. Experts discussed parameters such as study endpoints, duration, enrollment criteria, patient-reported outcomes, recruitment, and retention. The discussions among the experts, FDA, and audience members should help to facilitate the development and evaluation of reasonably safe and effective myopia control devices.

Contact Lens-Related Corneal Infections - United States, 2005-2015.

Keratitis (inflammation of the cornea) can result from contact lens wear or other causes. Keratitis from all causes, including contact lens wear, results in approximately 1 million clinic and emergency department visits annually, with an estimated cost of $175 million in direct health care expenditures in 2010 (1). Approximately 41 million U.S. residents wear contact lenses, and in 2014, >99% of contact lens wearers surveyed reported at least one behavior that puts them at risk for a contact lens-related eye infection (2). The Center for Devices and Radiological Health at the Food and Drug Administration (FDA) regulates contact lenses as medical devices, and certain adverse events related to contact lenses are reported to FDA's Medical Device Report (MDR) database. To describe contact lens-related corneal infections reported to the FDA, 1,075 contact lens-related MDRs containing the terms "ulcer" or "keratitis" reported to FDA during 2005-2015 were analyzed. Among these 1,075 reports, 925 (86.0%) were reported by a contact lens manufacturer and 150 (14.0%) by an eye care provider or patient. Overall, 213 (19.8%) reports described a patient who had a central corneal scar, had a decrease in visual acuity, or required a corneal transplant following the event. Among the reports, 270 (25.1%) described modifiable factors known to be associated with an increased risk for contact lens-related corneal infections, including sleeping in contact lenses or poor contact lens hygiene; the remainder did not provide details that permitted determination of associated factors. Continued efforts to educate contact lens wearers about prevention of contact lens-related eye infections are needed.

A Health-Related Quality of Life Measure for Patients Who Undergo Minimally Invasive Glaucoma Surgery.

PURPOSE: To develop a standardized patient-reported outcome measure to assess the impact of glaucoma and treatment, including minimally invasive glaucoma surgery (MIGS), on health-related quality of life (HRQOL). DESIGN: Observational study before and after concomitant cataract and FDA-approved implantable MIGS device surgery to provide information on the measure's performance in assessing HRQOL. METHODS SETTING: Survey administration was done by electronic patient-reported outcomes (ePRO) application to patients at multiple sites on a computer, iPad, or similar device. PATIENT POPULATION: One hundred eighty-four adults completed a baseline survey, 124 completed a survey 3 months after surgery, and 106 completed the 1-month test-retest reliability survey. The age range was 37-89, and the average age was 72. Most of the respondents were female (57%), non-Hispanic White (81%), and had a college degree (56%). MAIN OUTCOME MEASURES: The Glaucoma Outcomes Survey (GOS) includes 42 questions assessing functional limitations (27 items), vision-related symptoms (7 items), psychosocial issues (7 items) and satisfaction with microinvasive glaucoma surgery (1 item). The three multiple-item scales were scored on a 0-100 range, with a higher score indicating worse health. RESULTS: Internal consistency reliability estimates ranged from 0.75 (vision-related symptoms) to 0.93 (functional limitations) and one-month test-retest intraclass correlations ranged from 0.65 (PROMIS global mental health) to 0.92 (functional limitations). Product-moment correlations among the GOS scales ranged from 0.56 to 0.60. Improvement in visual acuity in the study eye from baseline to the 3-month follow-up was significantly related to improvements in GOS functional limitations (r =0.18, p =0.0485), vision-related symptoms (r = 0.19, p = 0.0386), and psychosocial concerns (r = 0.18, p =0.0503). The highest proportion of responders to treatment was seen for the GOS functional limitations scale (48%), followed by GOS psychosocial issues (21%) and GOS vision-related symptoms (17%). CONCLUSIONS: This study provides initial support for using the GOS instrument in ophthalmic procedures such as MIGS. Further evaluation of the GOS in other samples, including different patient subgroups and clinical settings, will be valuable. The instrument may be useful for evaluations of other treatments for glaucoma.

Communicating medical device recalls: A rapid review of the literature.

OBJECTIVES: The U.S. Food and Drug Administration (FDA) currently regulates more than 190,000 different medical devices. Like all products, these devices may be subject to manufacturing problems, flawed designs, or new and unexpected risks, which in some cases require devices to be recalled. In 2021, the FDA's Patient Engagement Advisory Committee (PEAC) recommended that the FDA consider changes to the communication approach used for medical device recalls to make them more patient-focused, timely, and action-oriented. METHODS: To support this recommendation, we conducted a rapid review of literature published from 2008-2022 to capture and examine information on risk communication approaches, methods, and best practices for recall-related communications about medical products. RESULTS: We identified 23 articles to include in our review. CONCLUSION: Our review found a lack of research-based studies as well as gaps in understanding about consumer perspectives, comprehension, and communication preferences related to recalls. Despite these limitations, we identified current communication approaches, numerous challenges, and recommendations for communicating medical products recall information to consumers. PRACTICE IMPLICATIONS: Further research is needed to assess consumer attitudes, understanding, and preferences and to reach consensus on best practices for effectively communicating recall information to consumers of medical products.

Patient Preferences for Benefit and Risk Associated With High Intensity Focused Ultrasound for the Ablation of Prostate Tissue in Men With Localized Prostate Cancer.

INTRODUCTION: Food and Drug Administration must make decisions about emerging high intensity focused ultrasound (HIFU) devices that may lack relevant clinical oncologic data but present with known side effects. This study aims to capture patients' perspective by quantifying their preferences regarding the available benefit and important side effects associated with HIFU for localized prostate cancer. MATERIALS AND METHODS: Preferences for HIFU outcomes were examined using a discrete choice experiment survey. Participants were asked to choose a preferred treatment option in 9 choice questions. Each included a pair of hypothetical treatment profiles that have similar attributes/outcomes with varying levels. Outcomes included prostate biopsy outcome and treatment-related risks of erectile dysfunction (ED) and urinary incontinence (UI). We calculated the maximum risk of side effect patients were willing to tolerate in exchange for increased benefit. Preferences were further explored via clinical and demographic data. RESULTS: About 223 subjects with a mean age of 64.8 years completed the survey. Respondents were willing to accept a 1.51%-point increase in new ED risk for a 1%-point increase in favorable biopsy outcome. They were also willing to accept a 0.93%-point increase in new UI risk for a 1%-point increase in biopsy outcome. Subjects who perceived their cancer to be more aggressive had higher risk tolerance for UI. Younger men were willing to tolerate less ED risk than older men. Respondents with greater than college level of education had a lower risk tolerance for ED or UI. CONCLUSIONS: Results may inform development and regulatory evaluation for future HIFU ablation devices by providing supplemental information from the patient perspective.

Non-Fusion Versus Fusion Surgery in Pediatric Idiopathic Scoliosis: What Trade-Offs in Outcomes Are Acceptable for the Patient and Family?

BACKGROUND: Vertebral body tethering and other non-fusion techniques for the treatment of pediatric idiopathic scoliosis are increasing in popularity. There is limited physician consensus on this topic as the result of a paucity of published data regarding which patients most benefit from non-fusion strategies. Thus, much of the decision-making is left to patients and parents, who must select a treatment based on their goals and values and the information available from health-care providers, the internet, and social media. We sought to understand patient and family preferences regarding the attributes of fusion versus non-fusion surgery that drive these choices. METHODS: Patients and families were recruited from 7 pediatric spine centers and were asked to complete a survey-based choice experiment that had been jointly developed with the U.S. Food and Drug Administration (FDA) to evaluate patient preferences. Choices between experimentally designed alternatives were analyzed to estimate the relative importance of outcomes and requirements associated with the choice options (attributes). The attributes included appearance, confidence in the planned correction, spinal motion, device failure, reoperation, and recovery period. The inclusion criteria were (1) an age of 10 to 21 years and (2) a diagnosis of adolescent idiopathic scoliosis in patients who were considering, or who had already undergone, treatment with fusion or non-fusion surgery. Preference weights were estimated from the expected changes in choice given changes in the attributes. RESULTS: A total of 344 respondents (124 patients, 92 parents, and 128 parent/patient dyads) completed the survey. One hundred and seventy-three patients were enrolled prior to surgery, and 171 were enrolled after surgery. Appearance and motion were found to be the most important drivers of choice. For the entire cohort, fusion was preferred over non-fusion. For patients who were considering surgery, the most important attributes were preservation of spinal motion and appearance. CONCLUSIONS: Patients and families seeking treatment for idiopathic scoliosis value appearance and preservation of spinal motion and, to a lesser extent, reoperation rates when considering fusion versus non-fusion surgery.

Using Separate Single-Outcome Risk Presentations Instead of Integrated Multioutcome Formats Improves Comprehension in Discrete Choice Experiments.

INTRODUCTION: Despite decades of research on risk-communication approaches, questions remain about the optimal methods for conveying risks for different outcomes across multiple time points, which can be necessary in applications such as discrete choice experiments (DCEs). We sought to compare the effects of 3 design factors: 1) separated versus integrated presentations of the risks for different outcomes, 2) use or omission of icon arrays, and 3) vertical versus horizontal orientation of the time dimension. METHODS: We conducted a randomized study among a demographically diverse sample of 2,242 US adults recruited from an online panel (mean age 59.8 y, s = 10.4 y; 21.9% African American) that compared risk-communication approaches that varied in the 3 factors noted above. The primary outcome was the number of correct responses to 12 multiple-choice questions asking survey respondents to identify specific numbers, contrast options to recognize dominance (larger v. smaller risks), and compute differences. We used linear regression to test the effects of the 3 design factors, controlling for health literacy, graph literacy, and numeracy. We also measured choice consistency in a subsequent DCE choice module. RESULTS: Mean comprehension varied significantly across versions (P < 0.001), with higher comprehension in the 3 versions that provided separated risk information for each risk. In the multivariable regression, separated risk presentation was associated with 0.58 more correct responses (P < 0.001; 95% confidence interval: 0.39, 0.77) compared with integrated risk information. Neither providing icon arrays nor using vertical versus horizontal time formats affected comprehension rates, although participant understanding did correlate with DCE choice consistency. CONCLUSIONS: In presentations of multiple risks over multiple time points, presenting risk information separately for each health outcome appears to increase understanding. HIGHLIGHTS: When conveying information about risks of different outcomes at multiple time points, separate presentations of single-outcome risks resulted in higher comprehension than presentations that combined risk information for different outcomes.We also observed benefits of presenting single-outcome risks separately among respondents with lower numeracy and graph literacy.Study participants who scored higher on risk understanding were more internally consistent in their responses to a discrete choice experiment.

Patient Preferences Regarding Surgical Treatment Methods for Symptomatic Uterine Fibroids.

STUDY OBJECTIVE: The purpose of this study is to rank the factors that are most and least important to patients with symptomatic uterine fibroids when considering surgical treatment options. MATERIALS AND METHODS: Using a best worst scaling (BWS) preference elicitation approach, participants completed an online survey to rank factors associated with fibroid surgical treatments. Survey content was based on a literature review and included the following factors: symptom relief; surgical complications; repeat treatment; recovery time; cosmetic effects; risk of spreading undiagnosed cancer; sexual outcomes; maintenance of child-bearing; continuation of menses; unpredictable menses; and location of procedure. Participants completed 11 BWS tasks. For each task, we presented participants with a subset of 5 factors from the possible 11, and participants chose the most important and least important factor. Participants' responses were analyzed using conditional logistic regression to determine the relative importance of factors. Patient priorities were further explored via age and race. RESULTS: 285 respondents with symptomatic uterine fibroids (69 physician-confirmed and 216 self-reported) who had not undergone prior surgical treatment completed the survey. Respondents were enrolled from two clinical sites (clinical site cohort) and an online consumer panel (panel cohort). Both cohorts identified symptom relief, cancer risk, repeat treatment and complications as the most important factors in selecting surgical treatment options and location of procedure, return to normal activities after surgery, and cosmetic effects like presence of a scar after the surgical treatment as the least important factors. Of note, younger women (≤ 40) placed greater importance on the ability to have children after the procedure. CONCLUSION: Information regarding the factors most and least important to patients with symptomatic uterine fibroids might inform development and regulatory evaluation of new technologies and procedures. Study results may be useful in efforts to develop a set of outcomes to include in future fibroids clinical studies.

Considerations for addressing bias in artificial intelligence for health equity.

Health equity is a primary goal of healthcare stakeholders: patients and their advocacy groups, clinicians, other providers and their professional societies, bioethicists, payors and value based care organizations, regulatory agencies, legislators, and creators of artificial intelligence/machine learning (AI/ML)-enabled medical devices. Lack of equitable access to diagnosis and treatment may be improved through new digital health technologies, especially AI/ML, but these may also exacerbate disparities, depending on how bias is addressed. We propose an expanded Total Product Lifecycle (TPLC) framework for healthcare AI/ML, describing the sources and impacts of undesirable bias in AI/ML systems in each phase, how these can be analyzed using appropriate metrics, and how they can be potentially mitigated. The goal of these "Considerations" is to educate stakeholders on how potential AI/ML bias may impact healthcare outcomes and how to identify and mitigate inequities; to initiate a discussion between stakeholders on these issues, in order to ensure health equity along the expanded AI/ML TPLC framework, and ultimately, better health outcomes for all.

Integrating Patient-Generated Health Data Throughout the Total Product Life Cycle of Medical Devices.

Nearly ubiquitous use of personal electronics, wearable sensors, and other types of digital health technologies, along with wireless connectivity, makes the capture of health data directly from an individual easier, enabling the use of patient-generated health data (PGHD) as a potential bridge between a patient's home and the healthcare system. This type of real-world data may be a completely new type of information, or it may be a more frequent collection of traditional information over longer time periods to form a longitudinal view of a patient's health status that can inform decision-making in clinical, medical product regulatory, and coverage and reimbursement settings. The U.S. Food and Drug Administration's Center for Devices and Radiological Health (CDRH) has been exploring and advancing the collection and use of PGHD since 2016, hosting a public meeting on the topic in May 2021. This manuscript presents highlights from various discussions at this meeting including those on the importance of stakeholder engagement, characteristics of high data quality, and PGHD in practice in patient-driven registries, as well as a look forward to some of the opportunities in the field.