Shared Decision-Making in Patients With Prostate Cancer in Japan: Patient Preferences Versus Physician Perceptions.

This article adds the Japanese perspective to our knowledge of shared decision-making (SDM) preferences by surveying patients with prostate cancer (PCA) and physicians in Japan. In 2015, 103 Japanese patients with PCA were asked about their SDM preferences by using an Internet-based 5-point-scale questionnaire. Concurrently, 127 Japanese physicians were surveyed regarding their perceptions of patient preferences on SDM. Drivers of preferences and perceptions were analyzed using univariable ordinal logistic regression and graphing the fitted response probabilities. Although 41% of both patients and physicians expressed and expected a desire for active involvement in treatment decisions (a higher rate than in a similar study for the United States in 2001), almost half the Japanese patients preferred SDM, but only 33% of physicians assumed this was their choice. That is, 29% of Japanese physicians underestimated patients' preference for involvement in making treatment decisions. Patients with lower health-related quality of life (as measured by the Functional Assessment of Cancer Therapy-Prostate [FACT-P]) expressed a stronger preference for SDM. The study shows that the worse the medical situation, the more patients with PCA prefer to be involved in the treatment decision, yet physicians tend to underestimate the preferences of their patients. Perhaps in contrast to common assumptions, Japanese patients are as interested in being involved in decision making as are patients in the United States.

Patient Preferences and Urologist Judgments on Prostate Cancer Therapy in Japan.

The purpose of the present study is to investigate the concordance of treatment preferences between patients and physicians in prostate cancer (PCa) in Japan. An internet-based discrete choice experiment was conducted. Patients and physicians were asked to select their preferred treatment from a pair of hypothetical treatments consisting of four attributes: quality of life (QOL), treatment effectiveness, side effects, and accessibility of treatment. The data were analyzed using a conditional logistic regression model to calculate coefficients and the relative importance (RI) of each attribute. A total of 103 PCa patients and 127 physicians responded. The study looked at 37 patients considered as advanced PCa and 66 who were non-advanced PCa. All of the physicians were urologists. Advanced PCa patients ranked the attributes as follows: treatment effectiveness (RI: 32%), accessibility of treatment (RI: 26%), QOL (RI: 23%), and side effects (RI: 19%). For physicians, the RI ranking was the same as for advanced PCa patients; treatment effectiveness (RI: 29%), accessibility of treatment (RI: 27%), QOL (RI: 26%), and side effects (RI: 18%). For non-advanced PCa patients, accessibility of treatment ranked the highest RI (27%) and treatment effectiveness ranked as the lowest RI (14%). Our study suggests that the ranking of the attributes was consistent between advanced PCa patients and physicians. The most influential attribute was treatment effectiveness. Treatment preferences also vary by disease stage.

Long-term effect of galantamine on cognitive function in patients with Alzheimer's disease versus a simulated disease trajectory: an observational study in the clinical setting.

BACKGROUND: Long-term maintenance of cognitive function is an important goal of treatment for Alzheimer's disease (AD), but evidence about the long-term efficacy of cholinesterase inhibitors is sparse. To evaluate the long-term efficacy and safety of galantamine for AD in routine clinical practice, we conducted a 72-week post-marketing surveillance study. The effect of galantamine on cognitive function was estimated in comparison with a simulated disease trajectory. PATIENTS AND METHODS: Patients with mild-to-moderate AD received flexible dosing of galantamine (16-24 mg/day) during this study. Cognitive function was assessed by the mini mental state examination (MMSE) and the clinical status was determined by the Clinical Global Impression-Improvement (CGI-I). Changes of the MMSE score without treatment were estimated in each patient using Mendiondo's model. Generalized linear mixed model analysis was performed to compare the simulated MMSE scores with the actual scores. RESULTS: Of the 661 patients who were enrolled, 642 were evaluable for safety and 554 were assessed for efficacy. The discontinuation rate was 46.73%. Cognitive decline indicated by the mean change of actual MMSE scores was significantly smaller than the simulated decline. Individual analysis demonstrated that >70% of patients had better actual MMSE scores than their simulated scores. Significant improvement of CGI-I was also observed during the observation period. Adverse events occurred in 28.5% of patients and were serious in 8.41%. The reported events generally corresponded with the safety profile of galantamine in previous studies. CONCLUSION: These findings support the long-term efficacy of galantamine for maintaining cognitive function and the clinical state in AD patients. Treatment with galantamine was generally safe. Importantly, this study revealed that galantamine improved cognitive function above the predicted level in >70% of the patients.

Use of Fentanyl Patch for Treatment of Moderate-to-severe Chronic Noncancer Pain: Postmarketing Surveillance of Medical Practice in Japan Using a Risk Minimization Action Plan.

OBJECTIVE: The purpose of this study was to discuss the safety, treatment profile, and clinical effectiveness of 12-month treatment with fentanyl patch (FP), a strong opioid, in medical practice in Japan under the risk minimization action plan (RMAP). METHODS: Patients with moderate-to-severe chronic noncancer pain who had switched to FP from another opioid were registered to take this survey to assess adverse drug reactions (ADRs), therapeutic effect, and pain intensity for up to 12 months. RESULTS: A total of 517 patients were enrolled, and 499 patients (male, 50.9%; mean [SD] age, 63.0 [15.4] years) were included in the safety population. During the 12-month observation period, an ADR occurred in 262 patients (52.5%); most frequent ADRs included nausea (24.2%), somnolence (22.4%), constipation (18.2%), vomiting (9%), and dizziness (4.6%). The prespecified priority survey items, including respiratory depression, drug dependence, and drug withdrawal syndrome, occurred in 2 (both nonserious), 3 (all serious), and 9 (all serious) patients, respectively. In 418 patients from the efficacy population, the response rate was 77.3%, the rate of achievement of the therapeutic goal was 64.5%, and the visual analog scale (VAS) scores for pain severity decreased by 22.3 (26.9) mm. CONCLUSION: Our results identified a reasonable risk-benefit profile for the management of moderate-to-severe chronic noncancer pain in patients previously treated with opioids under long-term treatment with FP under the RMAP. Respiratory depression, drug dependency, and drug withdrawal were rarely observed even under the RMAP in Japan.

Preferences Regarding Shared Decision-Making in Japanese Inflammatory Bowel Disease Patients.

INTRODUCTION: Recent studies have indicated that patients are showing increased interest in playing a larger role in making decisions regarding their medical treatment. Inflammatory bowel disease (IBD) is a chronic disease that manifests either as Crohn's disease (CD) or ulcerative colitis (UC). IBD treatment is multifaceted and dependent on patient-specific factors. The selection of treatment options is mostly driven by physicians, and it is unclear to what degree patients are involved in shared decision-making (SDM). The objective of the current study is to assess preferences among Japanese patients with IBD in regard to SDM during their treatment for IBD. METHODS: A nationwide web-based survey was performed in Japan during February 2016. The patients were asked for their basic clinical characteristics, socioeconomic status, medical history, treatment details, and preferences regarding SDM in IBD treatment. Differences were analyzed by chi-square, t tests, a multiple regression analysis, and ordered logistic regression analysis. RESULTS: In response to the screening survey, a total of 1068 Japanese nationals met the inclusion criteria for this study of being patients diagnosed with IBD who are currently receiving treatment. Of these, 235 had CD and 800 UC; 33 were not specified. Overall, the majority of these patients felt that SDM was very important. Furthermore, interest in SDM was strongly associated with certain disease comorbidities, surgical history, and current treatment, although there were some differences in the results between CD and UC. CONCLUSION: The present study found that the majority of IBD patients in Japan wanted to have a role in their treatment plan. The results indicate that the patient's preference in regard to SDM was driven by their perception of the severity or progression of their disease. FUNDING: Janssen Pharmaceuticals.

A comparison of overall survival with 40 and 50mg/m2 pegylated liposomal doxorubicin treatment in patients with recurrent epithelial ovarian cancer: Propensity score-matched analysis of real-world data.

BACKGROUND: In clinical practice, 40mg/m2 of pegylated liposomal doxorubicin (PLD40) has been used as an initial dosage for treating recurrent epithelial ovarian cancer (OC) instead of the recommended dose of 50mg/m2 (PLD50). However, no robust evidence is available to support the use of PLD40. This post-hoc study aimed to compare the efficacy and safety of initial PLD dosages in propensity score (P-score)-matched dataset. METHODS: The data source was a PLD postmarketing surveillance dataset (n=2189) conducted in Japan. Eligibility criteria for the present study were as follows: recurrent OC, history of chemotherapy, and treatment with PLD monotherapy at a dosage between 35.5 and 54.4mg/m2. Overall survival (OS) was compared between PLD50- and PLD40-treated groups using the log-rank test. Incidences of palmar-plantar erythrodysesthesia (PPE) and stomatitis were also compared between the groups. RESULTS: Overall, 503 matched pairs were generated using P-score analysis. The median survival time with PLD50 and PLD40 was 383 and 350days, respectively, with a hazard ratio of 1.10 (95% confidence interval, 0.98-1.26; p=0.211), although the difference was not statistically significant in the P-score-matched dataset. However, the incidence and severity of PPE and stomatitis were significantly lower with PLD40. CONCLUSIONS: Our study showed that the efficacy of PLD did not differ based on initial dosages, but the risk of adverse events was reduced with PLD40. Considering the balance between patient benefits and risks, our results support the use of PLD40 in clinical practice.

Association of early PSA decline and time to PSA progression in abiraterone acetate-treated metastatic castration-resistant prostate cancer; a post-hoc analysis of Japanese phase 2 trials.

BACKGROUND: Previous studies have demonstrated an association between prostate-specific antigen (PSA) kinetics and predictive value for treatment outcomes. Abiraterone acetate (AA) is a newly approved cytochrome-P450C17 inhibitor for treatment of metastatic castration-resistant prostate cancer (mCRPC), and few studies have evaluated PSA kinetics using AA so far. Results of a study evaluating PSA kinetics in the beginning of AA and enzalutamide responded chemotherapy-treated patients suggested different trends between the drugs. PSA kinetics of AA-treated patients has been reported using large datasets; however, no studies which have fully evaluated PSA kinetics in the beginning treatment. The present study aimed to assess the PSA kinetics and relationship between the PSA kinetics and PSA progression in chemotherapy-naïve and chemotherapy-treated mCRPC patients receiving AA. METHODS: We used two Japanese phase II trial datasets: JPN-201, chemotherapy-naïve mCRPC (n = 48) and JPN-202, chemotherapy-treated mCRPC (n = 46). PSA kinetic parameters were calculated using actual PSA values measured every 4 weeks, and a subgroup analysis was performed to evaluate the influence of early PSA response on time to PSA progression (TTPP). In addition, we used a Cox proportional hazard model to investigate the influence of variables on TTPP. RESULTS: PSA declined from week 4 but took more time to achieve nadir. PSA kinetic parameters were different between the datasets, mean time to PSA nadir was 5.3 ± 5.6 and 2.0 ± 3.4 months, and TTPP was 9.5 ± 7.4 and 3.8 ± 4.8 months in JPN-201 and JPN-202, respectively. In the subgroup analysis of week 4 PSA decline status, Kaplan-Meier curves for TTPP were similar between early responders and non-progression patients in JPN-201 (median, 9.2 vs. 6.5 months, respectively) but separated in JPN-202 (median, 3.7 vs. 1.9 months, respectively). According to univariate Cox regression analysis, achievement of PSA response (≥50 %) at week 12 was associated with TTPP in the both trials, but the hazard ratio of PSA decline (≥30 %) at week 4 was not significant in JPN-201. CONCLUSIONS: Our results suggest that PSA kinetics were not comparable and early PSA response showed different association to TTPP according to prior history of chemotherapy. TRIAL REGISTRATION: The original trials are registered at ClinicalTrials.gov. The identifiers are; JNJ-212082-JPN-201 , registered 20 December 2012 and JNJ-212082-JPN-202 , registered 30January 2013.

Estimation of minimal clinically important change of the Japanese version of EQ-5D in patients with chronic noncancer pain: a retrospective research using real-world data.

BACKGROUND: Quality of life (QoL) is routinely assessed and evaluated in medical research. However, in Japan, there is a lack of solid cutoff criteria for evaluating QoL improvement in chronic noncancer pain management. The present study was conducted to identify the minimal clinically important change (MCIC) of the Japanese version of EuroQol-5D 3L(EQ-5D) utility score and numeric rating scale (NRS) with an emphasis on chronic noncancer pain. METHODS: The data source for this post hoc research was the post-marketing surveillance (PMS) data for a tramadol/acetaminophen combination tablet, which was previously conducted in real-world settings. The parameters extracted from the PMS data were sociodemographic characteristics, NRS, EQ-5D, and dichotomous physician's global impression of treatment effectiveness (PGI). The optimal cutoff points of MCIC for EQ-5D utility and NRS scores were evaluated using receiver operating characteristics (ROC) analysis. An anchor-based approach using PGI was applied. RESULTS: Data of 710 patients with chronic noncancer pain were extracted from the PMS database. The NRS score decreased by 2.7 (standard deviation, 2.3) points, whereas the EQ-5D score increased by 0.16 (0.20) points at 4 weeks from baseline. The changes from baseline in NRS and EQ-5D were significantly correlated (r = 0.53, p < 0.001). The estimated optimal cutoff points of MCIC for EQ-5D and NRS were 0.10 and -2.0 points, respectively. The area under the curve of ROC was > 0.80 in both analyses. CONCLUSION: These results demonstrated novel cutoff criteria for the Japanese version of EQ-5D, focusing on patients with chronic noncancer pain. The obtained criteria were fairly consistent and can be confidently utilized as an evaluation tool in medical research on chronic noncancer pain in Japan, with additional functionality and usability for QoL assessment in pain management practice. TRIAL REGISTRATION: The data source of this post hoc research was a PMS study with the identifier number UMIN000015901 at umin.ac.jp, UMIN clinical trial registry (UMIN-CTR).

The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer's disease: a Bayesian network meta-analysis.

BACKGROUND: Comparative evidence for efficacy and safety of second-generation cholinesterase inhibitors (ChEIs) is still sparse. OBJECTIVES: The purpose of this research is to compare three ChEIs, donepezil, galantamine and rivastigmine, in patients with mild-to-moderate Alzheimer's disease (AD). METHODS: We conducted a systematic review for published articles and included randomised, double-blind, placebo-controlled trials and head-to-head randomised trials evaluating the efficacy and safety of ChEIs in patients with AD. We examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change (CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as safety profiles. Network meta-analyses were sequentially performed for efficacy and safety outcomes based on drug/dose treatment conditions. RESULTS: Among the 21 trials included, network meta-analysis showed that all treatments were significantly more efficacious than placebo in cognition measured by ADAS-Cog. All treatments except galantamine were significantly more efficacious than placebo in global change in CIBIC+ or CGIC. Across all conditions, no significant efficacy was observed in neuropsychiatric symptoms measured by NPI. Derived hierarchies in the efficacy of treatment conditions were variables across efficacy and safety. CONCLUSIONS: Our analysis is the first attempt to incorporate available direct and indirect evidence. The results suggest that ChEIs should have significant efficacy for cognition and global change assessment, but the efficacy on neuropsychiatric symptoms is questionable in patients with mild-to-moderate AD.

Predictive factors for 24 weeks sustained virologic response (SVR24) and viral relapse in patients treated with simeprevir plus peginterferon and ribavirin.

BACKGROUND: Simeprevir with peginterferon and ribavirin has been used for the treatment of chronic hepatitis caused by genotype 1 hepatitis C virus (HCV). We explored the predictive factors for sustained virological response (SVR) and viral relapse using datasets from four Japanese phase 3 studies (CONCERTO). METHODS: We used a multiple logistic regression model. First, an integrated dataset comprising 357 patients was analyzed. Subsequently, prior treatment-naïve and relapser (223 patients) and nonresponder (134 patients) of interferon-based treatment subsets were analyzed to identify predictors of SVR. A subset of nonresponders (106 patients) who were treated ≥24 weeks was also analyzed to identify predictors for viral relapse. RESULTS: In the integrated dataset, prior treatment response was significantly associated with SVR. In subset analyses, interleukin-28B (IL28B) TT genotype and undetectable plasma HCV RNA level at week 4 were associated in treatment-naïve patients and relapsers [odds ratio (OR); 4.106 and 3.701, respectively]. In the nonresponders, the IL28B TT genotype population was very small, and inosine triphosphatase (ITPA) and undetectable plasma HCV RNA at week 4 were associated (OR; 2.506 and 3.333, respectively). Furthermore, ribavirin dose intensity (RBV-DI) and detectable plasma HCV RNA at week 4 were significantly associated with viral relapse (OR; 0.327 and 2.922, respectively). CONCLUSION: IL28B and plasma HCV RNA level at week 4 were clinically relevant predictive factors for SVR in treatment-naïve patients and relapsers. Moreover, RBV-DI and plasma HCV level at week 4 were identified as relevant predictive factors for viral relapse in nonresponders.

The social functional outcome of being naturalistically treated with paliperidone extended-release in patients with schizophrenia.

BACKGROUND: Social functioning is an important outcome for patients with schizophrenia. To evaluate the effects of paliperidone extended-release (PAL-ER) on social function, symptomatology, and safety in the routine clinical practice, we conducted a 1-year post-marketing surveillance study of PAL-ER. We also explored relationships between symptomatic improvement and socially functional outcome in patients with schizophrenia. PATIENTS AND METHODS: Patients with an established diagnosis of schizophrenia were allowed flexible 3-12 mg/day dosing during the surveillance. Patients were assessed on social functioning using the Social and Occupational Functioning Assessment Scale (SOFAS) and on symptomatology using the Clinical Global Impression-Schizophrenia scale. All adverse events (AEs) were also collected. RESULTS: A total of 1,429 patients were enrolled in the surveillance study, of whom 1,405 were evaluable for safety and 1,142 were evaluable for efficacy. The treatment discontinuation rate for any reason during the observation period was 34.66%. Significant improvements were observed on both Social and Occupational Functioning Assessment Scale and Clinical Global Impression-Schizophrenia scale during the observation period. The percentage of patients with socially functional remission (SOFAS ≥61) also increased significantly. A significant association between early improvements in positive symptoms, sex, severity of negative symptoms at baseline, and socially functional remission was observed. A total of 33.52% of patients had AEs and 8.75% of patients had serious AEs. Despite the recommendation of monotherapy with PAL-ER, 65.84% of patients were given additional antipsychotics (polypharmacy). Post hoc comparisons of monotherapy versus polypharmacy revealed that the monotherapy group had better outcomes and fewer AEs than the polypharmacy treated group. The improvement in social functioning and the rate of socially functional remission did not differ between groups. CONCLUSION: PAL-ER treatment showed effective symptom control and improvement in social functioning. The data suggest that early response to antipsychotic treatment should be important for functional outcomes.

Bortezomib therapy-related lung disease in Japanese patients with multiple myeloma: incidence, mortality and clinical characterization.

Because of the potentially high mortality rate (6.5%) associated with bortezomib-induced lung disease (BILD) in Japanese patients with relapsed or refractory multiple myeloma, we evaluated the incidence, mortality and clinical features of BILD in a Japanese population. This study was conducted under the Risk Minimization Action Plan (RMAP), which was collaboratively developed by the pharmaceutical industry and public health authority. The RMAP consisted of an intensive dissemination of risk information and a recommended countermeasure to health-care professionals. All patients treated with bortezomib were consecutively registered in the study within 1 year and monitored for emerging BILD. Of the 1010 patients registered, 45 (4.5%) developed BILD, 5 (0.50%) of whom had fatal cases. The median time to BILD onset from the first bortezomib dose was 14.5 days, and most of the patients responded well to corticosteroid therapy. A retrospective review by the Lung Injury Medical Expert Panel revealed that the types with capillary leak syndrome and hypoxia without infiltrative shadows were uniquely and frequently observed in patients with BILD compared with those with conditions associated with other molecular-targeted anticancer drugs. The incidence rate of BILD in Japan remains high compared with that reported in other countries, but the incidence and mortality rates are lower than expected before the introduction of bortezomib in Japan. This study describes the radiographic pattern and clinical characterization of BILD in the Japanese population. The RMAP seemed clinically effective in minimizing the BILD risk among our Japanese population.