Adopting Weight-Based Dosing With Pharmacy-Level Stewardship Strategies Could Reduce Cancer Drug Spending By Millions

Immune checkpoint inhibitors, a class of drugs used in approximately forty unique cancer indications, are a sizable component of the economic burden of cancer care in the US. Instead of personalized weight-based dosing, immune checkpoint inhibitors are most commonly administered at one-size-fits-all flat doses that are higher than necessary for the vast majority of patients. We hypothesized that personalized weight-based dosing along with common stewardship efforts at the pharmacy level, such as dose rounding and vial sharing, would lead to reductions in immune checkpoint inhibitor use and lower spending. Using data from the Veterans Health Administration (VHA) and Medicare drug prices, we estimated reductions in immune checkpoint inhibitor use and spending that would be associated with pharmacy-level stewardship strategies, in a case-control simulation study of individual patient-level immune checkpoint inhibitor administration events. We identified baseline annual VHA spending for these drugs of approximately $537 million. Combining weight-based dosing, dose rounding, and pharmacy-level vial sharing would generate expected annual VHA health system savings of$74 million (13.7 percent). We conclude that adoption of pharmacologically justified immune checkpoint inhibitor stewardship measures would generate sizable reductions in spending for these drugs. Combining these operational innovations with value-based drug price negotiation enabled by recent policy changes may improve the long-term financial viability of cancer care in the US

Lorlatinib Exposed: A Far From Optimal Dose

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172839/1/cpt2579_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172839/2/cpt2579.pd

Targeted randomization dose optimization trials enable fractional dosing of scarce drugs.

Administering drug at a dose lower than that used in pivotal clinical trials, known as fractional dosing, can stretch scarce resources. Implementing fractional dosing with confidence requires understanding a drug's dose-response relationship. Clinical trials aimed at describing dose-response in scarce, efficacious drugs risk underdosing, leading dose-finding trials to not be pursued despite their obvious potential benefit. We developed a new set of response-adaptive randomized dose-finding trials and demonstrate, in a series of simulated trials across diverse dose-response curves, these designs' efficiency in identifying the minimum dose that achieves satisfactory efficacy. Compared to conventional designs, these trials have higher probabilities of identifying lower doses while reducing the risks of both population- and subject-level underdosing. We strongly recommend that, upon demonstration of a drug's efficacy, pandemic drug development swiftly proceeds with response-adaptive dose-finding trials. This unified strategy ensures that scarce effective drugs produce maximum social benefits

Real World Outcomes versus Clinical Trial Results of Durvalumab Maintenance in Veterans with Stage III Non-Small Cell Lung Cancer

One year of durvalumab following concurrent chemoradiotherapy improves progression-free (PFS) and overall survival (OS) for patients with stage III non-small cell lung cancer (NSCLC). However, the real-world efficacy of durvalumab has not been determined. We conducted a multi-center observational cohort study across the Veterans Health Administration, including patients with stage III NSCLC who received concurrent chemoradiotherapy and durvalumab, compared to patients who received concurrent chemoradiotherapy alone. Kaplan–Meier and Cox regression approaches were used to identify factors associated with PFS and OS. We calculated a hazard ratio and efficacy-effectiveness factor to compare OS of veterans to the referenced clinical trial population. A total of 1006 patients with stage III NSCLC who received concurrent chemoradiotherapy and at least one dose of durvalumab from November 2017 to April 2021 were compared to 989 patients who received concurrent chemoradiotherapy alone from January 2015 to December 2016. Adjuvant durvalumab was associated with higher PFS (HR 0.62, 95% CI 0.55–0.70, p p p = 0.02: EE gap 0.73). OS of veterans with stage III NSCLC treated with adjuvant durvalumab is improved compared to a modern comparator but is reduced compared to the PACIFIC population

Visual arts in the clinical clerkship: a pilot cluster-randomized, controlled trial

Abstract Background Arts exposure is associated with positive psychological constructs. To date, no randomized, controlled studies have integrated art into clinical medical education or measured its effects on positive psychological constructs or educational outcomes. In this study, we assessed the possibility and potential benefits of integrating visual arts education into a required internal medicine (IM) clinical clerkship. Methods We conducted a controlled trial in an academic healthcare system with an affiliated art museum. IM students were assigned to one of three interventions: museum-based arts (n = 11), hospital-based arts (n = 10), or hospital-based conventional education (n = 13). Arts groups explored empathy, resilience, and compassion in works of art during facilitator-guided discussions. We assessed pre- and post-intervention measures of empathy, mindfulness, tolerance of ambiguity, and grit and tracked National Board of Medical Examiners IM shelf exam performance to capture changes in educational outcomes. Focus group discussions with participants in the arts-based interventions were performed at the study’s conclusion. Results Arts education was successfully integrated into a busy clinical clerkship in both hospital and art museum settings. Focus group participants reported increased implicit bias cognizance and time for reflection, but no significant differences in psychometric or educational outcomes were identified. While most students felt positively toward the experience; some experienced distress from missed clinical time. Conclusions This pilot study demonstrates the feasibility of integrating visual arts education into the clerkship. Although observable quantitative differences in measures of positive psychological constructs and educational outcomes were not found, qualitative assessment suggested benefits as well as the feasibility of bringing fine arts instruction into the clinical space. A larger, multi-center study is warranted.http://deepblue.lib.umich.edu/bitstream/2027.42/173618/1/12909_2020_Article_2386.pd