The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer.

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .

Sample size determination for prediction models via learning-type curves.

This article is concerned with sample size determination methodology for prediction models. We propose to combine the individual calculations via learning-type curves. We suggest two distinct ways of doing so, a deterministic skeleton of a learning curve and a Gaussian process centered upon its deterministic counterpart. We employ several learning algorithms for modeling the primary endpoint and distinct measures for trial efficacy. We find that the performance may vary with the sample size, but borrowing information across sample size universally improves the performance of such calculations. The Gaussian process-based learning curve appears more robust and statistically efficient, while computational efficiency is comparable. We suggest that anchoring against historical evidence when extrapolating sample sizes should be adopted when such data are available. The methods are illustrated on binary and survival endpoints.

Playing by the Rules? Tracking U.S. Hospitals' Responses to Federal Price Transparency Regulation.

GOAL: As of January 1, 2021, the Centers for Medicare & Medicaid Services requires most U.S. hospitals to publish pricing information on their website to help consumers make decisions regarding services and to transform negotiations with health insurers. For this study, we evaluated changes in hospitals' compliance with the federal price transparency rule after the first year of enactment, during which the Centers for Medicare & Medicaid Services increased the penalty for noncompliance. METHODS: Using a nationally representative random sample of 470 hospitals, we assessed compliance with both parts of the hospital transparency rule (publishing a machine-readable price database and a consumer shopping tool) in the first quarter of 2022 and compared its baseline level in the first quarter of 2021. Using data from the American Hospital Association and Clarivate, we next assessed how compliance varied by hospital factors (ownership, number of beds, system membership, teaching status, type of electronic health record system), market factors (hospital and insurer market concentration), and the estimated change in penalty for noncompliance. PRINCIPAL FINDINGS: By early 2022, 46% of hospitals had posted both machine-readable and consumer-shoppable data, an increase of 24% from the prior year. Almost 9 in 10 hospitals had complied with the consumer-shoppable data requirement by early 2022. Larger hospitals and public hospitals had lower probabilities of baseline compliance with the machine-readable and consumer-shoppable requirements, respectively, although public hospitals were significantly more likely to become compliant with the consumer-shoppable requirement by 2022. Higher hospital market concentration was also associated with higher baseline compliance for both the machine-readable and consumer-shoppable requirements. Furthermore, our analyses found that hospitals with certain electronic health record systems were more likely to comply with the consumer-shoppable requirement in 2021 and became increasingly compliant with the machine-readable requirement in 2022. Finally, we found that hospitals with a larger estimated penalty were more likely to become compliant with the machine-readable requirement. PRACTICAL APPLICATIONS: Longitudinal analyses of compliance with the federal price transparency rule are valuable for monitoring changes in hospitals' behavior and assessing whether compliance changes vary systematically for specific types of hospitals and/or market structures. Our results suggest a trend toward increased hospital compliance between 2021 and 2022. Although hospitals perceive the consumer-shopping tools as being the most impactful, the value of this information depends on whether it is comprehensible and comparable across hospitals. The new price transparency rule has facilitated the creation of new data that have the potential to significantly alter the competitive landscape for hospitals and may require hospital leaders to consider how their organizational strategies change concerning their engagement with payers and patients. Finally, greater price transparency is likely to bolster national policy discussions related to price variation, affordability, and the role of regulation in healthcare markets.