Backgrounds Limited information is available on the utility values of metastatic pancreatic cancer, focusing on diferent health statuses, selected chemotherapy, and related grades 1/2 and 3/4 adverse ...events (AEs). We evaluated Japanese societal-based health-related utility values for metastatic pancreatic cancer by considering diferent grade toxicities commonly associated with chemotherapy using the vignette-based method. Methods We developed health status scenarios for patients with metastatic pancreatic cancer undergoing chemotherapy and conducted utility research using the developed scenarios in four steps: "literature review," "exploratory interview," "content validation", and "utility research". In the development process, to consider the impact of AEs of chemotherapy for metastatic pancreatic cancer on health state utility values, we selected neutropenia, febrile neutropenia, diarrhea, nausea and vomiting, and neuropathy as representative AEs. Each AE was classifed as either grade 1/2 or 3/4. We confrmed our created scenarios through cognitive interviews with the general population and clinical experts to validate the content. Finally, we developed 11 scenarios for using "utility research," evaluated in a societalbased valuation study using the face-to-face method. Participants for "utility research" were the general population, and they evaluated these scenarios in the composite time trade-of (cTTO) and visual analog scale (VAS) of the European quality of life (EuroQol) valuation technology to derive health state utility scores. Results Of 220 responders who completed this survey, 201 were adapted into the analysis population. Stable disease with no AEs (reference state) had a mean utility value of 0.653 using cTTO. The lowest mean utility score in the stable state was 0.242 (stable disease + grade 3/4 vomiting). VAS results ranged from 0.189 to 0.468, depending on the various grades of AEs in stable disease. In addition, grade 3/4 AEs and grade 1/2 nausea/vomiting were associated with signifcantly greater disutility. Utility values were also strongly infuenced by the direct impact of AE on physical symptoms, severity and their experience. In addition, 95.9% of the respondents agreed that they understood the questions in the post-response questionnaire. Conclusions We clarifed the health state utility values of patients with metastatic pancreatic cancer based on the general population in Japan. The efect on utilities should be considered not only for serious AEs, but also for minor AEs.
Background
This study aimed to clarify the treatment patterns of pancreatic cancer patients receiving systemic chemotherapy in Japan and to estimate the direct medical costs in actual practice.
...Research Design and Methods
This retrospective cohort study used electronic health record data between April 2008 and December 2018 in Japan. Participants had a confirmed pancreatic cancer diagnosis and received at least one systemic chemotherapy, including FOLFIRINOX, gemcitabine plus nab‐paclitaxel, gemcitabine, and S‐1. The outcomes were treatment patterns and monthly medical costs and the distribution of monthly medical costs across healthcare resource categories.
Results
Of the 4514 selected patients, 40.7%, 7.1%, 24.4%, and 21.3% used gemcitabine plus nab‐paclitaxel, FOLFIRINOX, gemcitabine, and S‐1 as first‐line chemotherapy, respectively. The median monthly medical costs were the highest in the first month, with gemcitabine plus nab‐paclitaxel ranking first (6813 USD), followed by FOLFIRINOX, gemcitabine, and S‐1. The health resource categories with the highest shares of monthly medical costs during the first‐line treatment period with gemcitabine plus nab‐paclitaxel and FOLFIRINOX were hospitalization costs (FOLFIRINOX: 41%–37%; gemcitabine plus nab‐paclitaxel: 40%–34%) and medicine costs (FOLFIRINOX: 51%–42%; gemcitabine plus nab‐paclitaxel: 49%–38%).
Conclusions
This study sheds light on the current treatment patterns and direct medical costs of systemic chemotherapy for pancreatic cancer in Japan.
Utilization pancreatic cancer chemotherapy
Various first-line chemotherapy treatment regimens for patients with metastatic pancreatic cancer have been approved in Japan, including gemcitabine (GEM); fluorouracil, leucovorin, irinotecan, and ...oxaliplatin combination (FOLFIRINOX); GEM plus albumin-bound paclitaxel (GEM+NPTX), and S-1 (tegafur + gimeracil + oteracil). However, direct comparisons of these chemotherapy regimens are limited.
To assess the short-term and long-term outcomes associated with first-line chemotherapy regimens for metastatic pancreatic cancer compared with chemotherapy regimens recommended in Japanese guidelines.
In this systematic review and network meta-analysis, the bibliographic databases PubMed, Cochrane Library, and Web of Science, as well as medical journals published between January 1, 2002, and December 31, 2018, were searched for clinical trials comparing chemotherapy regimens.
Randomized 2-arm clinical trials evaluating first-line chemotherapy for advanced or metastatic pancreatic cancer were included.
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions was followed for data abstractions. Data were pooled using a random-effects model. The SIGN 50 Quality Assessment Instrument was used to assess the risk of bias and overall study quality of the selected trials.
The primary end point was overall survival (OS), and the secondary end point was progression-free survival (PFS) compared with GEM for first-line chemotherapy for metastatic pancreatic cancer. The Kaplan-Meier curve of GEM from the literature and the estimated hazard ratios (HRs) were used to model the long-term associations to calculate the area under the curve (AUC) (person-months) for OS and PFS of each chemotherapy. Sensitivity analyses with multiple functional models were conducted to confirm the long-term estimations.
A total of 22 regimens (25 studies) for OS and a total of 18 regimens (21 studies) for PFS were identified from literature. The total number of participants was 10 186, with 5856 male (57.5%) and 4330 female (42.5%). The FOLFIRINOX and GEM+NPTX regimens were associated with reduction in the risk of death, with an HR of 0.57 (95% CI, 0.41-0.79) and 0.72 (95% CI, 0.55-0.95) compared with GEM, respectively. The curve estimation also showed that FOLFIRINOX had the largest AUC for survival at 15.49 person-months (range, 13.84-15.51 person-months), followed by GEM+NPTX with 12.36 person-months (range, 10.98-12.59 person-months), GEM+ERLO with 10.84 person-months (range, 9.66-11.23 person-months), S-1 with 8.44 person-months (range, 8.26-9.74 person-months), and GEM with 8.10 person-months (range, 7.93-9.38 person-months).
The results of this network meta-analysis support the relative short-term and long-term outcomes associated with first-line chemotherapy for metastatic pancreatic cancer used clinically in Japan.
Background Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, conducting a QOL survey with patients is difficult. Therefore, we conducted a QOL survey with ...physicians. Specifically, this study aimed to clarify how physicians assess QOL in patients with pancreatic cancer by conducting a survey and comparing the results between physicians and the general public. Methods A survey was conducted by interviewing physicians administering chemotherapy to patients for recurrent/metastatic pancreatic cancer. This method is similar to that of the QOL survey conducted among the general public. Responses were evaluated using the composite time trade-off (cTTO) and the visual analog scale (VAS) for 11 pancreatic cancer status scenarios (survey scenarios). These scenarios consisted of patients’ health states as well as the types and grades of adverse events (AEs). Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). In addition, we conducted a survey using the EuroQol 5 Dimensions 5-Level (EQ-5D-5l) as reference values. Results Twenty physicians responded to the survey. SD had the highest mean QOL value for both assessment methods (Physicians: 0.78, General public: 0.63), whereas PD had the lowest mean QOL value (Physicians: 0.15, General public: −0.12). The physicians assigned higher QOL values on both the VAS and cTTO than the general public did in all survey scenarios. Conclusions The QOL values obtained from physicians were consistent with the degree of status in any assessment scenarios. Based on the differences in the QOL survey results between physicians and the general public, physicians tended to assign higher QOL values than the general public in cTTO and VAS assessments.
Every year, the National Institute of Public Health (NIPH) conducts "Pharmaceutical Hygiene Management Training" as training course for pharmaceutical inspectors belonging to 47 prefectures and PMDA ...to carry out GMP inspections. In this training, which is held every year for 5 weeks, in addition to the classroom training, mock inspections are conducted with the cooperation of the pharmaceutical plants. In the fiscal year 2021, we gathered online in May 2021 for classroom lectures (3 weeks), preparations for mock inspections and on-site inspections (1 week), and then compiled the report. At that time, we examined whether online inspection could be done. With the cooperation of the pharmaceutical plants, an online inspection was also conducted in hybrid style among three training teams.As a result of conducting a hybrid style mock inspection exercise with 5 participants in the field and 7 participants online, we convinced the possibility of online inspection as an efficient inspection method by making improvements, although there are various restrictions.We hope that this experience will lead to the possibility of online inspections in the future, and we report this time.
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Background: Pancreatic cancer and especially late-line chemotherapy often negatively impact patient quality of life (QoL). However, QoL outside of the date of hospital visits has not been ...adequately evaluated. This study assessed QoL at home in patients receiving chemotherapy using electronic patient-reported outcomes (ePRO). Methods: This multicenter prospective observational study was conducted in 29 Japanese centers. Pathologically confirmed unresectable pancreatic cancer patients who were going to receive a second cycle of second-line chemotherapy, liposomal irinotecan plus fluorouracil/leucovorin (nal-IRI+FF), gemcitabine plus nab-paclitaxel (GEM+nab-PTX), or gemcitabine alone (GEM) at the outpatient department were included. QoL was assessed by electronic instruments on days 1, 2, 4, 6, 8, and 11 of each administration during two consecutive cycles (second and third cycles). The primary outcome was the index value of EuroQol 5-dimensions 5-levels (EQ-5D-5L). Secondary outcomes were the status of the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C30 and Patient-Reported Outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE). Results: A total of 90 patients, 56 receiving nal-IRI+FF, 27 receiving GEM+nab-PTX, and 7 receiving GEM, were eligible for this study. The patients who responded to at least the first questionnaire and received nal-IRI+FF (n = 46) or GEM+nab-PTX (n = 16) were selected for analysis. In the nal-IRI+FF group, the mean index value of EQ-5D-5L on day 1 of the second cycle was 0.803±0.142, declined up to day 6 (0.678±0.247), and had recovered by day 1 of the third cycle (0.776±0.197). Similar trends were observed in the third cycle; the nadir of the mean index value was 0.723±0.182 on day eight and had recovered by day 15 (0.782±0.159). On the other hand, in the GEM+nab-PTX group, the nadir of the mean index value in the second cycle was on day 6 of the third administration (0.751±0.184) and had not fully recovered by day 1 of the third cycle (0.789±0.182). For global health status according to EORTC-QLQ-C30, a similar trend to EQ-5D-5L was observed in both groups. According to the results of the PRO-CTCAE, pain (40.4%), diarrhea (36.5%), abdominal pain (30.8%), fatigue (28.8%), and anorexia (28.8%) were frequent severe or very severe adverse events in the nal-IRI+FF group. In comparison, diarrhea (29.2%) and anorexia (25.0%) were frequent severe or very severe adverse events in the GEM+nab-PTX group. Conclusions: QoL assessed by ePRO outside the date of hospital visits revealed the pattern or details of QoL transition. Further study is needed so that these trends can be taken into account in the management of chemotherapy. Clinical trial information: UMIN000044245 .
Background and Objective
Trastuzumab is a standard care as adjuvant chemotherapy (AdjCT) for patients with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer (BC) in ...Japan. However, no reports have evaluated its economics for patients with HER2-positive BC over 70 years of age. The objective of this study was to evaluate the cost-effectiveness of HER2-targeted trastuzumab + chemotherapy in Japan, comparing it with trastuzumab monotherapy.
Methods
A three-state-partitioned survival model was developed to evaluate the cost-effectiveness of trastuzumab + chemotherapy versus trastuzumab monotherapy for AdjCT in elderly patients with HER2-positive BC. We derived the efficacy data, utilities, and costs of both arms from individual patient data in the RESPECT trial (NCT01104935) and published studies. The costs and quality-adjusted life years (QALYs) were discounted at 2% per annum using a payer perspective. The respective cost estimates were reported in 2019 Japanese Yen (JPY) or US dollars (US$). The primary outcome was the incremental cost-effectiveness ratio (ICER). We assured robustness with deterministic and probabilistic sensitivity analyses.
Results
The cost per patient for trastuzumab + chemotherapy was JPY 14.6 million (US$137,000), and their QALYs were 9.308, compared with JPY 14.2 million (US$131,000) and 9.101, respectively, for trastuzumab monotherapy. The ICER of trastuzumab + chemotherapy versus trastuzumab monotherapy was JPY 2.7 milllion/QALY (US$17,200/QALY). The ICER for trastuzumab with chemotherapy varied from "Dominant" to "Dominated" in one-way sensitivity analysis.
Conclusions
The base-case analysis suggests that AdjCT with trastuzumab + chemotherapy is likely to be a cost-effective choice for patients with HER2-positive BC aged 70 years or older. However, the sensitivity analysis suggested uncertainty regarding the cost-effectiveness of trastuzumab + chemotherapy.
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