2015) Design of exponential control charts based on average time to signal using a sequential sampling schemeExponential charts based on time-between-events (TBE) data are widely investigated and applied in various fields. The average time to signal (ATS) is used instead of the average run length to evaluate the performance of TBE charts, since the ATS involves both the number and the time of samples inspected until a signal occurs. An ATS-unbiased exponential control chart is proposed when the in-control parameter is known. Considering the need in practice to start monitoring a production process as soon as possible, a sequential sampling scheme is adopted and the in-control parameter is estimated by an unbiased and consistent estimator. Some specific guidelines to stop updating control limits are obtained from the relationship between the phase I sample size and the actual false alarm rate. Finally, two real examples are given to illustrate the implementation and efficiency of the proposed method.

BackgroundRapidly evolving understanding of cancer biology has presented novel opportunities to translate that understanding into clinically relevant therapy. Palbociclib, a novel, first-in-class cyclin-dependent kinase (CDK) 4/6 inhibitor was approved in the USA in February 2015 for the treatment of advanced/metastatic breast cancer. We examined real-world evidence in the first year post approval to understand the clinical and demographic characteristics of patients treated with palbociclib in community oncology practices and the dosing, treatment, and complete blood count (CBC) monitoring patterns.MethodsThis was a retrospective observational study of structured data from a US electronic medical record (EMR) database. Female patients receiving palbociclib after 31 January 2015 were followed through 31 March 2016. Our methodological rules were constructed to aggregate drugs received according to the order in which they are given, i.e., identify the line of therapy as first, second, or third line, etc., using treatment order and course description fields from the EMR.ResultsThere were 763 patients initiating palbociclib who met the selection criteria. Of those, 612 (80.2%) received palbociclib concomitantly with letrozole. Mean follow up was 6.4 months and mean age at palbociclib initiation was 64 years. Of patients with a known starting dose (n = 417), 79.9% started on palbociclib 125 mg. Dose reductions were observed in 20.1% of patients. Percentages of patients according to line of therapy at initiation of palbociclib were first-line, 39.5%; second-line, 15.7%; third-line, 13.1%; and fourth-line therapy or later, 31.7%. On average, two CBC tests were conducted during the first cycle of palbociclib treatment. Overall, 74.6% of patients had a neutropenic event during follow up including 47.3% and 8.0% of patients with a grade 3 or 4 occurrence, respectively.ConclusionsReal-world palbociclib use one year post US approval demonstrates a more heterogeneous patient population than that studied in the clinical trials with more than half of the patients receiving palbociclib plus letrozole in later lines of therapy. CBC testing rates suggested good provider compliance with monitoring guidelines in the USA prescribing information. The occurrence of grade 3 and 4 neutropenia (based on laboratory results) was consistent with the rates of grade 3 and 4 neutropenia in two phase-III studies (PALOMA-2, 56% and 10%; PALOMA-3, 55% and 11%, respectively). Understanding palbociclib utilization in real-world patients and how drug dosing and monitoring are performed aids in the understanding of safe and effective use of the drug.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-0958-2) contains supplementary material, which is available to authorized users.

Gamma charts for time between events are very useful in the high‐quality processes, which monitor the time until the rth event. The average time to signal (ATS) is adopted to evaluate the performance of Gamma charts, because it reflects both the number and the sampling interval of samples inspected until an out‐of‐control signal occurs. An ATS‐unbiased design for Gamma charts with known parameters is proposed based on the hypothesis test of the scale parameter. For the phase I monitoring, a new ATS‐unbiased design with unknown parameters is developed, and a sequential sampling scheme is adopted to start process monitoring as soon as possible. Some specific guidelines to stop updating the control limits are suggested from the convergence of the width between control limits with different phase I sample sizes. Finally, a real example is illustrated to demonstrate the implementation of the proposed approach. Copyright © 2015 John Wiley & Sons, Ltd.

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