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Purpose: There is a lack of real‐world data in Asian populations for brigatinib, a next‐generation anaplastic lymphoma kinase (ALK) inhibitor for patients with non‐small cell lung cancer (NSCLC). This study analysed real‐world outcomes and dosing patterns for brigatinib in patients with crizotinib‐refractory ALK+ NSCLC in South Korea. Methods: This retrospective, non‐interventional, cohort study used South Korean Health Insurance and Review Assessment claims data for adults with ALK+ NSCLC who initiated brigatinib between 19 April 2019 and 31 March 2021 after receiving prior crizotinib. Patients' characteristics, time to discontinuation (TTD), time to dose reduction, overall survival (OS) and treatment adherence were assessed. Results: The study included 174 patients (56.9% male; 27.0% with a history of brain metastases). Median duration of prior crizotinib was 17 (range 0.3–48) months. Median follow‐up after brigatinib initiation was 18 (range 0–34) months. Overall, 88.5% of patients received full‐dose brigatinib (180 mg/day) and 93.1% of patients were adherent (proportion of days covered ≥0.8). The median TTD was 24.9 months (95% CI 15.2–not reached). The probability of continuing treatment was 63.2% at 1 year and 51.5% at 2 years. The probability of continuing at full or peak dose was 79.7% at 1 year and 75.6% at 2 years. Median OS was not reached. The 2‐year OS rate was 68.7%. Conclusions: In this first nationwide retrospective study using national insurance claim data, brigatinib demonstrated real‐world clinical benefit as second‐line treatment after prior crizotinib in ALK+ NSCLC patients in South Korea. [ABSTRACT FROM AUTHOR]

In this paper, two observability measures are introduced for a discrete linear system. The degrees of observability of both the system and its subspaces can be examined with these measures. The measures are well conditioned to perturbation and applicable to multi-input/multi-output time-varying systems. The relations among observability, observability measures, error covariance, and the information matrix are presented. It is shown that the measures have direct connections with the singular value decomposition of the information matrix. In contrast to the error covariance, the measures are determined by the system model and independent of the initial error covariance. An example of the observability analysis of the Global Positioning System/Inertial Navigation System is given. The measures are confirmed to be less sensitive to the system model perturbation. It is also shown that the vertical component of the gyro bias can be considered unobservable with a tactical-grade inertial measurement unit for a horizontal constant-speed motion. Index Terms--Global Positioning System (GPS), inertial navigation, observability measure, singular value decomposition (SVD).

Lever-arm uncertainty can be an important error source in the integration of the Global Positioning System (GPS) and inertial navigation system (INS). This paper presents both numerical and experimental studies on the estimation of the lever arm in the integration of a very-low-grade inertial measurement unit (IMU) with an accurate single-antenna GPS measurement system. Covariance simulation results showed that maneuvers play an important role on the estimation of the lever arm and attitude. The length of the lever arm has a rather insignificant effect on the estimation of these. Experimental tests conducted with a low-cost microelectromechanical system (MEMS) IMU and a carrier-phase differential GPS (CDGPS) measurement system showed that the lever arm can be estimated with centimeter-level accuracy. The test results confirmed that angular motions and horizontal accelerations improve the estimates of the lever arm and yaw angle, respectively. Index Terms--Global positioning system (GPS), inertial measurement unit (IMU), inertial navigation, inertial navigation system (INS), lever arm, observability.

Observability properties of errors in an integrated navigation system are studied with a control-theoretic approach in this paper. A navigation system with a low-grade inertial measurement unit and an accurate single-antenna Global Positioning System (GPS) measurement system is considered for observability analysis. Uncertainties in attitude, gyro bias, and GPS antenna lever arm were shown to determine unobservable errors in the position, velocity, and accelerometer bias. It was proved that all the errors can be made observable by maneuvering. Acceleration changes improve the estimates of attitude and gyro bias. Changes in angular velocity enhance the lever arm estimate. However, both the motions of translation and constant angular velocity have no influence on the estimation of the lever arm. A covariance simulation with an extended Kalman filter was performed to confirm the observability analysis. Index Terms--Global Positioning System, GPS/INS, inertial measurement unit (IMU), inertial navigation, lever arm, observability.

Purpose: The benefit-risk balance for drugs can alter post approval owing to additional data on efficacy or adverse events. This study developed a quantitative benefit-risk assessment (BRA) model for statins using multicriteria decision analysis with discrete choice experiments and compared a recent BRA with that at the time of approval.Patients and Methods: Following a systematic review of the literature, the benefit criteria within the statin BRA model were defined as a reduction in the plasma low-density lipoprotein cholesterol level and a reduction in myocardial infarction incidence; the risk criteria were hepatotoxicity (Liv) and fatal rhabdomyolysis (Rha). The scores for these criteria were estimated using mixed treatment comparison methods. Weighting was calculated from a discrete choice experiment involving 203 Korean patients. The scores and weights were integrated to produce an overall value representing the benefit-risk balance, and sensitivity analyses were conducted.Results: In this BRA model, low-density lipoprotein (relative importance [RI]: 37.50%) was found to be a more important benefit criterion than myocardial infarction (RI: 35.43%), and Liv (RI: 16.28%) was a more important risk criterion than Rha (RI: 10.79%). Patients preferred atorvastatin, and the preference ranking of cerivastatin and simvastatin was switched post approval because of the emergence of additional risk information related to cerivastatin.Conclusion: A quantitative statin BRA model confirmed that the preference ranking of statins changed post approval because of the identification of additional benefits or risks. [ABSTRACT FROM AUTHOR]

Purpose: The benefit-risk balance for drugs can alter post approval owing to additional data on efficacy or adverse events. This study developed a quantitative benefit-risk assessment (BRA) model for statins using multicriteria decision analysis with discrete choice experiments and compared a recent BRA with that at the time of approval., Patients and Methods: Following a systematic review of the literature, the benefit criteria within the statin BRA model were defined as a reduction in the plasma low-density lipoprotein cholesterol level and a reduction in myocardial infarction incidence; the risk criteria were hepatotoxicity (Liv) and fatal rhabdomyolysis (Rha). The scores for these criteria were estimated using mixed treatment comparison methods. Weighting was calculated from a discrete choice experiment involving 203 Korean patients. The scores and weights were integrated to produce an overall value representing the benefit-risk balance, and sensitivity analyses were conducted., Results: In this BRA model, low-density lipoprotein (relative importance [RI]: 37.50%) was found to be a more important benefit criterion than myocardial infarction (RI: 35.43%), and Liv (RI: 16.28%) was a more important risk criterion than Rha (RI: 10.79%). Patients preferred atorvastatin, and the preference ranking of cerivastatin and simvastatin was switched post approval because of the emergence of additional risk information related to cerivastatin., Conclusion: A quantitative statin BRA model confirmed that the preference ranking of statins changed post approval because of the identification of additional benefits or risks.

Purpose: To elucidate and compare benefit-risk preferences among Korean patients and physicians concerning cyclooxygenase-2 (Cox-2) inhibitor treatments for arthritis., Materials and Methods: Subjects included 100 patients with arthritis and 60 board-certified orthopedic surgeon physicians in South Korea. Through a systematic review of the literature, beneficial attributes of using Cox-2 inhibitors were defined as a decrease in the Western Ontario and McMaster Universities Arthritis Index for pain score and improvement in physical function. Likewise, risk attributes included upper gastrointestinal (GI) complications and cardiovascular (CV) adverse events. Discrete choice experiments were used to determine preferences for these four attributes among Korean patients and physicians. Relative importance and maximum acceptable risk for improving beneficial attributes were assessed by analyzing the results of the discrete choice experiment by using a conditional logit model., Results: Patients ranked the relative importance of benefit-risk attributes as follows: pain reduction (35.2%); physical function improvement (30.0%); fewer CV adverse events (21.5%); fewer GI complications (13.4%). The physicians' ranking for the same attributes was as follows: fewer CV (33.5%); pain reduction (32.4%); fewer GI complications (18.1%); physical function improvement (16.0%). Patients were more willing than physicians to accept risks when pain improved from 20% or 45% to 55% and physical function improved from 15% or 35% to 45%., Conclusion: We confirmed that patients and physicians had different benefit-risk preferences regarding Cox-2 inhibitors. Patients with arthritis prioritized the benefits of Cox-2 inhibitors over the risks; moreover, in comparison with the physicians, arthritis patients were more willing to accept the trade-off between benefits and risks to achieve the best treatment level. To reduce the preference gap and achieve treatment goals, physicians must better understand their patients' preferences.