Regulating Laboratory Tests: What Framework Would Best Support Safety and Validity?

Policy Points With increasing public attention to cases of inaccurate and misleading laboratory-developed tests, there have been calls for regulatory reform. To protect patients from faulty laboratory tests, we need a framework that balances comprehensive test review with laboratory flexibility. The Verifying Accurate Leading-edge IVCT [In Vitro Clinical Test] Development (VALID) Act would have helped ensure laboratory test safety and validity through a much-needed expansion of Food and Drug Administration (FDA) oversight. However, Congress did not pass the VALID Act in 2022, forcing the FDA to start the regulatory reform process on its own.

Patent Portfolios Protecting 10 Top-Selling Prescription Drugs.

Importance: Brand-name drugs are sold at high prices in the US during market exclusivity periods protected by patents. Multiple overlapping patents protecting a drug are known as patent thickets and can effectively delay the emergence of price-lowering generic competition for many years. Objective: To evaluate the composition of patent thickets of 10 top-selling prescription drugs in the US and compare the characteristics of drug patents filed during development with those filed on these products after US Food and Drug Administration (FDA) approval. Design and Setting: This cross-sectional study examined US patent thickets of the 10 prescription drugs with the highest US net sales revenue in 2021 using information on issued patents and patent applications as of June 30, 2022, obtained from a public database by the Initiative for Medicines, Access, and Knowledge. Data were analyzed from September 2022 to June 2023. Main Outcomes and Measures: Prevalence of patents filed before and after FDA approval; types of claims present in issued patents (ie, chemical composition, method of use, process or synthesis, formulation, and delivery device); and patent thicket density (number of active patents at a given time). Results: The 10 top-selling prescription drugs in the US for 2021 included 4 small-molecule drugs and 6 biologics. These 10 drugs were linked to 1429 patents and patent applications: 742 (52%) issued patents, 218 (15%) pending applications, and 469 (33%) abandoned applications. Almost three-quarters of patent applications (1028 [72%]) were filed after FDA approval. The postapproval proportion was higher for biologics (80%) than for small-molecule drugs (58%). Postapproval filing of patent applications peaked in the first 5 years after FDA approval for small-molecule drugs and 12 years after FDA approval for biologics. Of 465 patents issued for applications filed after FDA approval, 189 (41%) had method of use claims, 127 (27%) had formulation claims, and 103 (22%) had process or synthesis claims, while 86 (19%) had chemical composition claims and 46 (10%) had device claims. Patent thicket density peaked 13 years after FDA approval, at which time these 10 drugs were protected by a median (IQR) of 42 (18-83) active patents, 66% of which were filed after FDA approval. Conclusions and Relevance: This study found that among the 10 top-selling prescription drugs in the US in 2021, patents filed after FDA approval and containing claims covering aspects other than the active ingredient of the drug contributed to patent thickets. Scrutiny of patent applications and of patents filed after FDA approval is needed to facilitate timely generic or biosimilar competition.

Confronting High Costs And Clinical Uncertainty: Innovative Payment Models For Gene Therapies.

Gene therapies offer potentially life-changing benefits for patients, but their unprecedented high prices exacerbate challenges for reimbursement. Payers must confront high budgetary impacts, as a large up-front payment for each patient makes it difficult to predict and absorb costs. Payers also face considerable clinical uncertainty, as evidence for efficacy and durability is limited at approval. Alternative payment models may address these reimbursement problems and ensure equitable patient access. We developed a taxonomy of possible payment mechanisms for gene therapies, including installments, risk pools, reinsurance, price-volume agreements, expenditure caps, subscriptions, outcomes-based payments and rebates, warranties, population outcomes-based agreements, and coverage with evidence development. We illustrate how these payment models take three main approaches: amortization, which mitigates initial budget impact by spreading payments over time; risk spreading, which makes budgets more predictable by pooling costs with other payers or capping costs based on expected volume; and performance-based payment, which addresses clinical uncertainty by tying prices to patient- or population-level outcomes. We discuss each payment model, its advantages and challenges, and considerations for US payers.

Measuring Attitudes About Genomic Medicine: Validation of the Genomic Orientation Scale (GO Scale).

OBJECTIVES: Assessing public attitudes about genomic medicine is critical for anticipating patient receptivity to clinical applications of genomics. Although scholars have highlighted the importance of assessing stakeholder opinions and views regarding advances in clinical genomics, to date there has not been a robust tool for measuring these attitudes. We designed a study to evaluate the validity of an instrument we developed for measuring attitudes about genomic medicine. METHODS: We used psychometric methods to validate the Genomic Orientation Scale (GO Scale). Our goal was to create an easy-to-use tool for evaluating positive and negative attitudes about genomic medicine. RESULTS: We describe the validation testing of the GO Scale in a nationally representative sample of 1536 individuals residing in the United States. We report results from convergent and divergent validity testing and Rasch modeling analysis. The study produced a 26-item scale with 2 dimensions-optimism and pessimism. CONCLUSIONS: The GO Scale may be used to characterize attitudinal perspectives among patients, clinicians, and the public. The GO Scale may also be useful in evaluating shifts in attitude over time, for example, following educational interventions, which has not been feasible to date.

Examining Physician Interactions with Disease Advocacy Organizations.

Disease advocacy organizations (DAOs) have traditionally focused on raising awareness of rare diseases, providing educational resources to patients, and supporting patients and families. Previous research has described how scientists collaborate with DAOs, but few empirical data are available regarding the extent to which physicians interact with DAOs and how those interactions impact patient care. We conducted a national survey of 230 board-certified pediatric neurologists to assess their engagement with DAOs and their beliefs about the impact of DAOs on patient care. In that context, we evaluated a set of 24 items describing interactions between physicians and DAOs. Exploratory factor analysis produced a 19-item model capturing four types of physician-DAO engagement: (1) accessing or distributing DAO-produced materials (6 items, alpha = 0.80); (2) consulting on DAO activities (5 items, alpha = 0.81); (3) collaborating with DAOs on research activities (6 items, alpha = 0.80); and (4) co-producing scholarly materials with DAOs (2 items, alpha = 0.80). Our data indicate that physicians engage with DAOs in more frequent and diverse ways than has been previously reported. Almost all physicians in our sample had interacted directly with a DAO in some way, from low-effort activities such as visiting a DAO's website to deeper forms of engagement including coauthoring journal articles. These findings may provide a framework for bioethicists to characterize the nature and extent of physician interactions with advocacy organizations, which is critical for evaluating the ethical implications of physician-DAO relationships.

Perceptions and Preferences About Granular Data Sharing and Privacy of Behavioral Health Patients.

Little is known about data sharing preferences for care and research of behavioral health patients. Eighty-six behavioral health patients (n = 37 Latinos; n = 32 with serious mental illness) completed questionnaires, in either English or Spanish, with items assessing their views on privacy and sensitivity of health record information. Most patients (82.5%) considered mental health information as sensitive. In general, there was a direct correspondence between perceived sensitivity of information and willingness to share with all or some providers. A main motivation for sharing data with providers was improving the patient's own care (77.8%). Most participants (96.5%) indicated they would be extremely to somewhat willing to share their data for research with their care facilities and universities. Follow-up patient interviews are being conducted to further elucidate these findings.

Design and Pilot Testing of an English and Spanish Behavioral Health Patient Survey on Data Privacy.

We piloted a Spanish and English survey on data privacy. Thirty-one Latino behavioral health patients completed the survey in person with a preference for paper (78%) over electronic questionnaire. Dialect variations across Latino countries and the lack of tools to assess reading level in Spanish affected comprehension. Our experience will help others address similar tasks more effectively and encourage inclusion of Latino populations in future research.

Assessing optimism and pessimism about genomic medicine: Development of a genomic orientation scale.

Efforts to characterize stakeholder attitudes about the implementation of genomic medicine would benefit from a validated instrument for measuring public views of the potential benefits and harms of genomic technologies, which would facilitate comparison across populations and clinical settings. We sought to develop a scale to evaluate attitudes about the future of genomic medicine. We developed a 21-item scale that examined the likelihood of various outcomes of genomic medicine. The scale was administered to participants in a genomic sequencing study. Exploratory factor analysis was conducted and bivariate correlations were calculated. The genomic orientation (GO) scale was completed by 2895 participants. A two-factor structure was identified, corresponding to an optimism subscale (16 items, α = 0.89) and a pessimism subscale (5 items, α = 0.63). Genomic optimism was positively associated with a perceived value of genetic test results, higher health literacy, and decreased decisional conflict about participation in a genomic research study. Genomic pessimism was associated with concerns about genetic testing, lower health literacy, and increased decisional conflict about the decision to participate in the study. The GO scale is a promising tool for measuring both positive and negative views regarding the future of genomic medicine and deserves further validation.

Should pretest genetic counselling be required for patients pursuing genomic sequencing? Results from a survey of participants in a large genomic implementation study.

PURPOSE: We assessed the decision-making of individuals pursuing genomic sequencing without a requirement for pretest genetic counselling. We sought to describe the extent to which individuals who decline genetic counselling reported decisional conflict or struggled to make a decision to pursue genomic testing. METHODS: We administered a 100-item survey to 3037 individuals who consented to the Return of Actionable Variants Empirical study, a genomic medicine implementation study supported by the National Institutes of Health (USA) eMERGE consortium. The primary outcomes of interest were self-reported decisional conflict about the decision to participate in the study and time required to reach a decision. RESULTS: We received 2895 completed surveys (response rate=95.3%), and of these respondents 97.8% completed the decisional conflict scale in its entirety. A majority of individuals (63%) had minimal or no decisional conflict about the pursuit of genomic sequencing and were able to reach a decision quickly (78%). Multivariable logistic regression analyses identified several characteristics associated with decisional conflict, including lower education, lower health literacy, lower self-efficacy in coping, lack of prior experience with genetic testing, not discussing study participation with a family member or friend, and being male. CONCLUSION: As genomic sequencing is used more widely, genetic counselling resources may not be sufficient to meet demand. Our results challenge the notion that all individuals need genetic counselling in order to make an informed decision about genomic sequencing.

Current State of Electronic Consent Processes in Behavioral Health: Outcomes from an Observational Study.

An integral element of value-based care is care team access to both physical and behavioral health data. Data release processes in both environments are governed by federal and state statutes. The requirements for obtaining consent are complex and often confusing. Little is known about the consent processes and practices in the behavioral health setting, specifically how patients and surrogates engage in the process and their interactions with electronic consent tools. This study analyzes the consent processes from the patient perspective at two community behavioral health clinics. Outcomes include description of the processes using electronic consent, workflows and consenter-provider interactions. Conclusions include need to streamline and standardize consent technologies and improve consenter engagement. This study supports the development of an electronic consent tool, My Data Choices (MDC), funded by the National Institute of Mental Health, that offers individuals with behavioral health conditions more control over their medical records.