Mark J. Ratain

Introduction: Clinical practice guidelines influence coverage policy, utilization management, and health care spending. In oncology, some function as drug compendia that guide Medicare coverage of off-label therapies, yet little empirical work has examined their governance. Methods: We conducted a cross-sectional descriptive study using publicly available documentation to evaluate responses to 75 standardized external change requests submitted to 26 National Comprehensive Cancer Network (NCCN) disease-site panels concerning pembrolizumab or nivolumab dosing. Requests concerning subcutaneous formulations served as a comparator. We characterized request disposition, review timing, transparency, scope interpretation, and financial conflict-of-interest (FCOI) context. Results: By March 6, 2026, 10 of 75 dosing-related requests (13%) had been adopted, 51 (68%) rejected or determined to be outside panel scope, and 14 (19%) remained pending (median time to decision, 190 days). In contrast, requests concerning FDA-approved subcutaneous formulations were adopted in 52 of 53 cases (98%) and reviewed substantially more rapidly (median, 11 days). Public documentation incompletely described panel deliberations, voting, participation, and management of financial conflicts of interest. Conclusions: Standardized requests revealed operational heterogeneity and limitations in publicly available documentation within a CMS-recognized compendium, identifying opportunities to strengthen transparency and governance in coverage-relevant decision making.

Pharmacogenomics (PGx) offers patients personalized treatment by guiding medication selection and dosing based on their genetic profiles. However, widespread clinical implementation remains limited, in part due to patient and provider concerns about cost and willingness to pay (WTP). This study evaluated whether an outpatient clinical consultation that educates patients on their PGx results influences their WTP for PGx testing. As part of the PROTECT‐Rx trial at the University of Chicago, high‐risk patients received free PGx testing and a virtual consultation at the Personalized Therapeutics Clinic (PTC). Patients completed pre‐ and post‐visit surveys assessing PGx knowledge and WTP. Of 129 patients who had completed a PTC visit as of 1/2025, 76 completed both the PTC visit and surveys. WTP for PGx testing increased significantly from 68% pre‐visit to 83% post‐visit ( p = 0.029). After controlling for social vulnerability, patients who had at least one cautionary or high‐risk PGx result were nearly 3 times more likely to report higher willingness‐to‐pay (OR 2.76, p = 0.037). A single PGx consultation with review of personal results significantly increases patients' WTP for testing, particularly among those with actionable PGx results. Understanding individual risk and the relevance of PGx enhances perceived value, suggesting that patient education is an important component in the broader adoption of pharmacogenomic testing.

PURPOSE: To assess the ongoing citation of the 2009 Nature Genetics article by Ross et al linking TPMT to cisplatin-induced ototoxicity and to evaluate the extent to which its disputed findings persist in the literature. METHODS: A total of 378 Google Scholar citations of the 2009 Nature Genetics publication from 2009 to 2025 were examined, of which 214 PubMed-indexed manuscripts were screened and categorized by citation nuance (positive, negative/mixed) and citation characteristics using the framework proposed by Suelzer et al in a 2019 JAMA Network Opens study. Citation context was independently assessed by two reviewers, with discrepancies resolved by consensus of all three authors. RESULTS: Most articles cited the 2009 publication in a favorable or uncritical manner, even in publications after 2015 US Food and Drug Administration's cisplatin label revision acknowledging that the 2009 findings were flawed. A minority of citations acknowledged conflicting evidence or questioned the study's validity. CONCLUSION: Although the 2009 publication's findings have been widely challenged, many subsequent authors continue to cite the study without acknowledging its limitations. This pattern highlights the need for stronger postpublication oversight, more transparent editorial practices by high-impact journals, and greater critical engagement by authors when citing foundational literature to ensure that clinical and research narratives are shaped by reliable and current evidence.

Optimal prescribing of drug products requires accurate informative drug labels. One critical aspect of a label is the recommended dosage. We suggest that the final authority for this portion of the label should reside in FDA's Office of Clinical Pharmacology (OCP), rather than in the Office of New Drugs, given that most FDA clinicians do not have sufficient expertise to interpret pharmacometric analyses of dose‐exposure, and dose/exposure‐efficacy/safety relationships.

Pharmacogenomics implementation efforts have increased over the last decade, but no published prospective pharmacogenomics trials have formally evaluated utility in underrepresented populations. We present final results from the ACCOuNT trial, a multi‐institutional prospective study [NCT03225820] in which African American inpatients were genotyped and pharmacogenomic results made available via an integrated, scalable pharmacogenomics clinical decision support (PGx CDS) system to guide prescribing. We hypothesized that PGx CDS utilization would improve genomically concordant prescribing during inpatient admissions. We recruited 531 patients, of which 187 were readmitted (60.4% female, median age = 55 [range: 19–88], median readmissions/patient = 2 [range: 1–17]), resulting in 518 evaluable admissions during which the effect of available pharmacogenomic results was measured. In 50% of admissions, care teams utilized PGx CDS. 12% of inpatient prescriptions had pharmacogenomic annotations, with only 3.6% pharmacogenomically associated with increased caution (“discordant”); no PGx high‐risk medications were prescribed. PGx CDS use by provider teams did not decrease genomically discordant prescribing (3.9% vs. 3.3% without PGx CDS use, P = 0.53). Nevertheless, inpatient care teams repeatedly consulted PGx CDS ostensibly to affirm genomically concordant prescriptions, as 48% of all admissions and 91% of discharges included pharmacogenomically annotated medications, mostly genomically concordant. Notably, timing of PGx CDS utilization correlated tightly with prescribing timing (correlation coefficient = 0.84, P < 0.05). In the first results of a multi‐institutional, prospective pharmacogenomics trial focused on underrepresented patients, we found the relevance of currently actionable pharmacogenomics information for guiding inpatient prescribing to be modest; but observed frequent use of concordant pharmacogenomics to affirm prescribing.