RESUMO
A cancer diagnosis is devastating for both patients and their caregivers. With high morbidity and mortality, cancer is a serious disease area with unmet medical needs. Thus, innovative anticancer drugs are in high demand worldwide but are unequally available. Our study focused on first-in-class (FIC) anticancer drugs and investigated their actual development situation in the United States (US), European Union (EU), and Japan over the last two decades to obtain fundamental information for understanding how the aforementioned demands are met, especially to eliminate drug lags among regions. We identified FIC anticancer drugs using pharmacological classes for the Japanese drug pricing system. Most FIC anticancer drugs were first approved in the US. The median approval time for anticancer drugs in new pharmacological classes during the last two decades in Japan (5072 d) was significantly different (p = 0.043) from that in the US (4253 d), though it was not significantly different from that in the EU (4655 d). Submission and approval lags between the US and Japan were more than 2.1 years, and those between the EU and Japan were more than 1.2 years. However, those between the US and the EU were less than 0.8 years. The development rate of FIC anticancer drugs in Japan is slower than in other regions. Even among developed countries, FIC anticancer drug lags exist. Considering the high impact of FIC anticancer drugs on society worldwide, we should work together to reduce drug lag among regions using an improved international cooperative framework.
Assuntos
Antineoplásicos , Neoplasias , Humanos , Estados Unidos , União Europeia , Aprovação de Drogas , Japão , Fatores de Tempo , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
Early access to novel drugs, regardless of regional differences, is significant for patients worldwide. Although various efforts have been made to reduce the drug lag, it still exists in some regions, including Japan. In this study, we focused on the drug lag of first-in-class drugs in Japan and obtained fundamental information because we considered that first-in-class and me-too drugs are essentially different and should be treated separately. We analyzed 97 first-in-class and 176 me-too drugs in new molecular entity (NME)-approved drugs in Japan and the United States during the fiscal years between 2009 and 2019. Since government policy and the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs (the Committee) have a huge impact on drug lag, we distinguished NMEs developed at the Committee's request. First-in-class drugs were developed at the Committee's request significantly more than the me-too drugs (p = 0.0034). Although it was not statistically significant, the approval lags were 498.0 d for first-in-class drugs and 535.0 d for me-too drugs. Multiple regression analysis showed that multi-regional clinical trial (MRCT) development strategy (p = 0.0043) and foreign origin drugs (p = 0.0072) were a reducing factor and a prolonging factor of drug lag, respectively. In conclusion, the drug lag for first-in-class drug approval was one year. Global drug development using MRCT is one of the most effective development strategies for reducing drug lags.
Assuntos
Aprovação de Drogas , Humanos , Japão , Análise Multivariada , Fatores de Tempo , Estados UnidosRESUMO
WHAT IS KNOWN AND OBJECTIVE: Although there are accelerated approval pathways based on data of small populations and surrogate endpoints, the concern that these pathways authorize the use of inefficacious drugs based on limited data from earlier phase clinical trials remains. We retrospectively investigated the efficacy of anticancer drugs, which were approved or whose development was terminated in small and large clinical trials, and verified whether small clinical trials could reflect the results for efficacy in large clinical trials. METHODS: All anticancer drugs approved in Japan or whose development was terminated from 2015 to 2019 were searched. The median overall survival (OS), median progression-free survival (PFS), and overall response rates (ORR) between small clinical trials (sample size ≤100) and large clinical trials (sample size >100) with identical target populations and treatment settings were compared. Simple linear regression analysis, Spearman's correlation analysis, and paired sample t-test were performed. RESULTS AND DISCUSSION: A total of 61 comparable small and large clinical trials were identified. For all endpoints, statistically significant linear trends and correlation were detected (p < 0.001). There were no statistically significant differences in the median PFS and ORR between small and large clinical trials. The mean differences of both clinical trials were -0.102 months and -1.531%, respectively. WHAT IS NEW AND CONCLUSION: Even when the sample size of the clinical trial was increased, the efficacy data of anticancer drugs could not be changed significantly. These results supported the accelerated approval pathway based on the promising efficacy data of small populations in anticancer drug development.
Assuntos
Antineoplásicos , Antineoplásicos/uso terapêutico , Biomarcadores , Ensaios Clínicos como Assunto , Humanos , Japão , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
WHAT IS KNOWN AND OBJECTIVE: Regulatory authorities in several regions have introduced a number of expedited programs (EPs) to promote the development of innovative drugs for patients in their own countries. The EPs in the United States (US), alone or in combination, have been successful in shortening the clinical development time in the US. We examined whether US-EPs, as well as other related factors, have an impact on the clinical development time in Japan to obtain new insights for more efficient drug development. METHODS: In total, 168 drugs approved as new molecular entities (NMEs) in Japan and approved in the US between 2012 and 2019 were surveyed. We compared the clinical development time in Japan for those drugs with or without US-EPs. We also examined the impact of overlapping designations of US-EPs on clinical development time in Japan. Multiple regression analysis was performed to identify associated factors related to clinical development time in Japan, including US-EPs. RESULTS AND DISCUSSION: The clinical development time in Japan was significantly shorter at 37.4 [Interquartile range, IQR, 28.7-48.9] months for Accelerated Approval (AA), 42.2 [30.0-53.6] months for Breakthrough Therapy (BT), 42.3 [29.3-56.4] months for Fast Track (FT), 44.5 [30.7-60.0] months for US Priority Review, and 45.2 [31.3-61.8] months for US Orphan Designation. Multiple regression analysis revealed that AA (p = 0.008), FT (p = 0.013), Japan Priority Review, and the difference in development initiation dates between the US and Japan were significant factors related to a decrease in the clinical development time in Japan, whereas Japan Orphan Designation and the development of anticancer drugs were significant factors linked to an increase in the clinical development time. WHAT IS NEW AND CONCLUSION: US-EPs were associated with a decrease in the clinical development time in Japan for the drugs that were approved as NMEs in Japan and approved in the US. This association was not restricted to particular therapeutic areas or development strategies. Stakeholders involved in drug development, including the drug developers and regulatory authorities in Japan, should realize these effects for efficient drug development.
Assuntos
Antineoplásicos , Aprovação de Drogas , Antineoplásicos/uso terapêutico , Desenvolvimento de Medicamentos , Humanos , Japão , Estados Unidos , United States Food and Drug AdministrationRESUMO
WHAT IS KNOWN AND OBJECTIVE: Drug development is generally a long and expensive process. Regulatory authorities have established several expedited regulatory pathways, such as accelerated approval designation in the United States (1992) and conditional approval regulation in Japan (2017). In Japan, prior to 2017, the Pharmaceutical and Medical Device Agency (PMDA) granted marketing approval without requesting the results of confirmatory clinical trials case by case basis, and even after 2018, only three drugs have been approved via the conditional approval pathway, although many drugs without confirmatory clinical trials have been approved without this pathway; therefore, it is difficult to predict the circumstances under which confirmatory clinical trials may be waived. The aim of this study was to investigate the characteristics of drugs for which the requirement of confirmatory clinical trials for approval was waived in Japan. We also aimed to identify factors and formulae to predict a waiver of confirmatory clinical trials. METHODS: Data on approved drugs and their characteristics were mainly extracted from the Japan Pharmaceuticals and Medical Device Agency database. The seriousness of the disease, existence of available treatments and number of patients were considered as candidate factors. The influence of each factor on receiving a waiver was determined using logistic regression analysis comparing drugs approved with and without confirmatory clinical trials as the binary response variable. The predictive formula was derived from the results of the logistic regression analysis. A receiver operating characteristic curve was used to evaluate the accuracy of the prediction. RESULTS AND DISCUSSION: Categorization of drugs as antineoplastic agents, use of the cost accounting method in the drug pricing system, "orphan" designation and accelerated approval designation in the United States emerged as significant factors in the logistic regression analysis, predicting a waiver for confirmatory clinical trials (p ≤ 0.05). These factors were then used to establish a predictive model to ascertain whether confirmatory clinical trials would be necessary for a new drug, exhibiting good sensitivity (0.8) and specificity (0.8) and high accuracy for newly approved drugs. WHAT IS NEW AND CONCLUSION: The identification of key factors that can predict waivers of confirmatory clinical trials may accelerate the development of clinically important drugs and improve patient access globally.
Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Aprovação de Drogas/estatística & dados numéricos , Humanos , JapãoRESUMO
The approval of orphan anticancer drugs in Japan has increased to meet high social demand. Drug lag, namely the approval lag of new drugs, is recognized as a social issue in Japan. We investigated the approval lag and its components, submission lag and review-time lag, between Japan and the United States (US) to reveal whether an approval lag still exists, and to identify potential factors that may contribute to reducing the approval lag. Anticancer drugs approved in Japan between April 2004 and November 2017 were investigated using publicly available information. Results showed that the median approval lag of orphan anticancer drugs in 2016-2017 was 727.0 days (interquartile range, IQR, 310.0-1054.3). The approval lag was significantly correlated with the submission lag (correlation coefficient = 1.00, P < 0.001) but not with the review-time lag (correlation coefficient = -0.16, P = 0.22). The submission lag was significantly longer for orphan anticancer drugs than non-orphan drugs (median, 712.5 days [IQR, 186.0-1448.3] vs. 387.0 days [92.8-1096.0], P = 0.023). External collaboration in drug development was associated with a longer submission lag (coefficient = 762.1, P = 0.017), while breakthrough therapy designation in the US was associated with a shorter submission lag (coefficient = -832.8, P = 0.035). In conclusion, we revealed that an approval lag for orphan anticancer drugs still existed in 2016-2017. A submission lag for orphan anticancer drugs was the main component affecting the approval lag, and was longer than that for non-orphan drugs. External collaboration in drug development may be a potential factor in reducing the submission lag for orphan anticancer drugs.
Assuntos
Antineoplásicos/uso terapêutico , Aprovação de Drogas/legislação & jurisprudência , Aprovação de Drogas/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Produção de Droga sem Interesse Comercial/legislação & jurisprudência , Ensaios Clínicos Fase III como Assunto , Humanos , Japão , Produção de Droga sem Interesse Comercial/estatística & dados numéricos , Fatores de Tempo , Estados Unidos , United States Food and Drug AdministrationRESUMO
The objective of this study was to analyze the relationship between the pharmacokinetic (PK)/pharmacodynamic (PD) parameters of a single 2-g dose of extended-release formulation of azithromycin (AZM-SR) and its microbiological efficacy against gonococcal urethritis. Fifty male patients with gonococcal urethritis were enrolled in this study. In 36 patients, the plasma AZM concentrations were measured using liquid chromatography-tandem mass spectrometry, the AZM MIC values for the Neisseria gonorrhoeae isolates were determined, and the microbiological outcomes were assessed. AZM-SR monotherapy eradicated N. gonorrhoeae in 30 (83%) of the 36 patients. AZM MICs ranged from 0.03 to 2 mg/liter. The mean value of the area under the concentration-time curve (AUC), estimated by population PK analysis using a two-compartment model, was 20.8 mg · h/liter. Logistic regression analysis showed that the PK/PD target value required to predict an N. gonorrhoeae eradication rate of ≥95% was a calculated AUC/MIC of ≥59.5. The AUC/MIC value was significantly higher in patients who achieved microbiological cure than in patients who achieved microbiological failure. Monte Carlo simulation using this MIC distribution revealed that the probability that AZM-SR monotherapy would produce an AUC/MIC exceeding the AUC/MIC target of 59.5 was 47%. Furthermore, the MIC distribution for strains isolated in this study was mostly consistent with that for strains currently circulating in Japan. In conclusion, in Japan, AZM-SR monotherapy may not be effective against gonococcal urethritis. Therefore, use of a single 2-g dose of AZM-SR either with or without other antibiotics could be an option to treat gonococcal urethritis if patients are allergic to ceftriaxone and spectinomycin or are diagnosed to be infected with an AZM-sensitive strain.
Assuntos
Antibacterianos/uso terapêutico , Azitromicina/farmacocinética , Azitromicina/uso terapêutico , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Uretrite/tratamento farmacológico , Adulto , Antibacterianos/farmacocinética , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/uso terapêutico , Gonorreia/microbiologia , Humanos , Japão , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Resultado do Tratamento , Uretrite/microbiologia , Adulto JovemRESUMO
PURPOSE: Postoperative adhesions can be prevented by the use of bioabsorbable anti-adhesion barriers. Although the occurrence of postoperative bowel obstruction is an important concern for patients, at the time of approval of anti-adhesion barriers, its effectiveness in preventing postoperative bowel obstruction had not been evaluated. We aimed to retrospectively evaluate the incidence of bowel obstruction after colectomy in patients with colon cancer using an insurance claims database. METHODS: This retrospective cohort study analyzed the data of colon cancer patients (between 2005 and 2017 from a national insurance claims database) who underwent colectomies to compare the proportion of individuals with postoperative bowel obstruction between the barrier and no barrier groups. RESULTS: Of the 587 patients who met the inclusion criteria, 308 and 279 patients were identified as the barrier and no barrier groups, respectively. The incidence of postoperative bowel obstruction was significantly lower in the barrier group (log-rank test, P = 0.0483). The cumulative incidence of postoperative bowel obstruction 37 months after the initial colectomy was 6.1% and 10.9% in the barrier and no barrier groups, respectively. Moreover, consistent results were obtained in the matched cohort. CONCLUSION: In colectomies for patients with colon cancer, the use of anti-adhesion barriers could significantly reduce the incidence of postoperative bowel obstruction. Evaluations using insurance claims databases could provide important information on outcomes following implementation of medical devices.
Assuntos
Colectomia , Neoplasias do Colo , Bases de Dados Factuais , Obstrução Intestinal , Complicações Pós-Operatórias , Humanos , Obstrução Intestinal/prevenção & controle , Obstrução Intestinal/etiologia , Neoplasias do Colo/cirurgia , Estudos Retrospectivos , Colectomia/efeitos adversos , Masculino , Feminino , Aderências Teciduais/prevenção & controle , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Implantes Absorvíveis , Incidência , AdultoRESUMO
Decisions concerning approval of human papillomavirus (HPV) vaccines and their use are based on expert evaluation of the vaccines. However, the quantitative differences between vaccine benefits and risks are difficult for non-experts to understand. In this study, we developed a new method to calculate the benefits and risks of the HPV vaccines using disability-adjusted life year (DALY) as the mono-scaled weight for various benefits and risks relevant to the vaccines. We evaluated benefits as a gain of DALY values for cervical cancer and risks as the loss of DALY values for various adverse events by the vaccination. To calculate the loss of DALY values, we integrated all adverse events in the International Classification of Diseases chapters. The novel method reflected the men-women ratio of this epidemiological disease to a certain extent. Among the vaccinated women, 111372 and 477190 received a bivalent and quadrivalent vaccine, respectively. The DALY rate of cervical cancer was 148.7. The calculated benefit for the bivalent and quadrivalent vaccines was 149.1 and 638.8, respectively, and set as the theoretical maximum. The risk was calculated as 129.3 and 49.6 in the bivalent and quadrivalent vaccines, respectively. Since HPV vaccines prevent several other cancers, the benefit of the vaccination extends beyond the risk according to this new method.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Masculino , Feminino , Humanos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Análise Custo-Benefício , Vacinação/métodos , Vacinas Combinadas , Medição de RiscoRESUMO
BACKGROUND: Drug time lags occur between the date that new drugs are first approved, often in the USA, and approval is granted in other countries. Multi-regional clinical trials (MRCTs) are a key strategy for simultaneous global development and regulatory submission of new drugs. However, no studies have evaluated the impact of MRCT versus local development on key time points in the drug development lifecycle between the USA and Japan. It is important for pharmaceutical companies planning drug development in Japan to understand when they can start development, when they can catch up in case of development initiation delay, length of time the development period might take, and amount of time that market exclusivity is lost, if Japan does not participate in the MRCT. OBJECTIVE: The aim of this study was to investigate differences in drug lag in development initiation, New Drug Application (NDA) submission and drug approval, as well as differences in the development and review periods, by local trials and MRCTs between Japan and the USA. We also assessed the advantages and disadvantages of MRCTs for these lags in Japan. METHODS: We analyzed drug approvals in Japan between 2016 and 2020 and divided them into local and MRCT groups. Lags in development initiation, NDA submission, and approval of new drugs were calculated by subtracting each date in Japan from the corresponding date in the USA. Our study period was divided into three periods based on the International Conference on Harmonization (ICH) E17 guideline, published in 2017, and the guideline for the Phase I trials in the Japanese population prior to MRCTs, published in 2014. In addition, subgroup analyses by therapeutic area, regulatory background, modality, capital style, and sales ranking (2020) were conducted. RESULTS: We analyzed 174 approvals in Japan and the USA. The differences in the drug lags for development initiation, NDA submission, and approval between the local and MRCT groups were 4.9, 3.5, and 3.2 years, respectively. All three lag times were shorter for the MRCT group than the local group. A development initiation lag in the local group has expanded since publication of the guidelines. CONCLUSIONS: For the people of Japan, important drug lags were identified in development initiation, NDA submission, and drug approval dates between local trials and MRCTs that include Japan. It is difficult to recover fully from the delay caused by local development, and it is important to understand the further expansion of drug lags, in cases where Japan is not involved in the MRCT.
Assuntos
Aprovação de Drogas , Preparações Farmacêuticas , Ensaios Clínicos como Assunto , Comércio , Humanos , JapãoRESUMO
BACKGROUND: The human papillomavirus (HPV) vaccine coverage is very low in Japan since the government suspended the active encouragement of the vaccination. We aimed to conduct a benefit-risk assessment of HPV vaccination and explore different consequent scenarios to identify potential improvements to the current Japanese immunization program. METHODS: To calculate social benefit-risk of HPV vaccine, we used the Markov model to represent the natural history of HPV and adverse events (AEs) using disability-adjusted life year (DALY) as the outcome. Benefits and risks were calculated as the sum of negative and positive outcomes corresponding to all preventable diseases and AEs associated with HPV vaccination, respectively. The benefit-risk balance in 2050 was estimated using published data. RESULTS: Our model was confirmed by published cervical cancer incidence and mortality rates. The benefit-risk balance in 2050 showed that the most effective scenario was the introduction of 9-valent HPV vaccine targeting female individuals aged 10-29 years for routine vaccination starting in 2020, although there is possibility of increased risks of AEs for the vaccinated age group post resumption of recommendations. CONCLUSION: Our benefit-risk assessment of HPV vaccine helped estimate various scenarios pertaining to HPV vaccination and identify the best strategy regarding HPV vaccination. This benefit-risk assessment approach may be used for other vaccines and vaccination programs.
Assuntos
Medição de Risco , Adolescente , Adulto , Criança , Análise Custo-Benefício , Feminino , Humanos , Japão , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Adulto JovemRESUMO
AIMS: As the population in Japan is rapidly aging, the prevalence of dementia, particularly Alzheimer's Disease (AD), is expected to increase, resulting in a growing need for caregivers. This study aims to quantify and compare the humanistic burden of caregivers of AD/dementia patients with caregivers of patients with other conditions in Japan. MATERIALS AND METHODS: This cross-sectional study used data from the 2018 Japan National Health and Wellness Survey (NHWS). Outcome measures included the Short-Form 12-item Health Survey (SF-12) for health-related quality-of-life (HRQoL), EuroQol 5-dimension scale (EQ-5D) for health states utilities, impact of health on productivity and activity, and evaluation of depression and anxiety. Multivariate analysis was used to compare across groups, with adjustment for potential confounding effects. RESULTS: A total of 805 caregivers of AD/dementia patients, 1,099 other caregivers, and 27,137 non-caregivers were identified. Both AD/dementia caregivers and other caregivers had lower HRQoL and EQ-5D scores, higher total activity impairment, and more caregivers tended to experience anxiety than non-caregivers. There were no significant differences in the involvment in basic and instrumental activities of daily living (ADL) between AD/dementia caregivers and caregivers of other conditions. Notably, AD/dementia caregivers were more involved in making treatment decisions and finance management than other caregivers. Among AD/dementia caregivers caring for one patient, 395 patients lived in the community and 282 in an institution. AD/dementia caregivers whose patients lived in the community were more significantly involved in basic and instrumental ADL. Caregivers of patients with both AD/dementia and cancer had higher caregiving burden than caregivers of patients with either condition. CONCLUSIONS: Caregivers of AD/dementia patients in Japan reportedly experienced significant humanistic burden which is associated with patients' living arrangements and the presence of an additional chronic condition. Therefore, provision of effective care/support is essential to relieve the burden experienced by the caregivers.
Assuntos
Doença de Alzheimer , Cuidadores , Atividades Cotidianas , Estudos Transversais , Humanos , JapãoRESUMO
AIMS: The growing prevalence of Alzheimer's disease (AD) worldwide has sparked the implementation of national policies to support the growing burden among caregivers of AD/dementia patients. This study aims to quantify and compare the burden of AD/dementia caregivers and evaluate how different living arrangements might impact health outcomes among caregivers in Japan, five European countries (5EU), and the United States (US). MATERIALS AND METHODS: This is a cross-sectional study based on existing data from the 2018 National Health and Wellness Survey. Health outcome measures included health-related quality of life (HRQoL), health state utilities, work productivity and activity impairment (WPAI), and measurement of depression and anxiety amongst AD/dementia caregivers and non-caregivers. Pairwise comparisons between AD/dementia caregivers in Japan, 5EU, and the US were conducted. Multivariate analysis was used to compare across groups within each region, with adjustment for potential confounding effects. RESULTS: A higher proportion of caregivers of AD/dementia patients in Japan were 65 years or older as compared to 5EU and US. On the contrary, female caregivers were significantly higher in the US than Japan and 5EU. The HRQoL and health state utilities index scores amongst AD/dementia caregivers were highest in Japan and lowest in the US. Caregivers in Japan incurred the lowest WPAI among the three regions. The proportion of AD/dementia patients reportedly living in an institution was highest in Japan as compared to the US and EU. Notably, US caregivers whose patients lived in an institution experienced significantly less caregiving burden as compared to caregivers whose patients lived in the community. CONCLUSIONS: The caregiving burden among AD/dementia caregivers was substantial across the three regions, with similarities and differences between the West and Japan. The lower caregiving burden in Japan was potentially associated with national policies supporting long-term healthcare and institutionalized nursing care facilities for AD/dementia patients.
Assuntos
Doença de Alzheimer , Cuidadores , Efeitos Psicossociais da Doença , Estudos Transversais , Feminino , Humanos , Japão , Qualidade de Vida , Estados UnidosRESUMO
AIMS: Patients with cancer experienced reduced health-related quality-of-life (HRQoL), increased work productivity and activity impairment (WPAI), and indirect costs. With the current emphasis on economic evaluation of health technology in Japan, it is important to understand how indirect costs correlate with HRQoL and patient characteristics. It is also crucial to assess the patient characteristics associated with the HRQoL, WPAI, and indirect costs among patients with any types of cancer. MATERIALS AND METHODS: This cross-sectional study used data from the 2017 Japan National Health and Wellness Survey (NHWS). Respondents self-reported their HRQoL and WPAI by answering validated SF-12v2 and WPAI questionnaires, respectively. Indirect costs were derived using the human capital method. Correlation between HRQoL components and indirect costs were assessed using Spearman's rank-order correlation. Correlation between patient characteristics and HRQoL, WPAI, and indirect costs were analyzed using generalized linear models. RESULTS: A total of 1,540 patients with any types of cancer, 254 with breast cancer, and 144 with colorectal cancer were included in the analyses. There was significant negative correlation between the indirect costs and HRQoL components among patients with any types of cancer. Patients with lower comorbid burden, higher household income, employed, married, or living with partner, never smokers, and exercised tended to have higher HRQoL. Being never smokers, having lower comorbid burden, normal weight, and exercised were associated with lower WPAI measures. Additionally, patients who were older, not married, not obese, and not smoking tended to incur lower indirect costs. CONCLUSIONS: The negative correlation between HRQoL and indirect costs among patients with cancer emphasized the needs to improve health outcomes and reduce indirect costs of patients. The factors associated with cancer burden identified in this study provide insights to allow targeted intervention to improve HRQoL and lessen the WPAI and indirect cost among cancer patients in Japan.
Assuntos
Neoplasias da Mama , Efeitos Psicossociais da Doença , Estudos Transversais , Feminino , Humanos , Japão , Qualidade de VidaRESUMO
Aims: Understanding the burden of cancer in Japan is becoming increasingly important to address the socio-economic consequences of the disease. This study broadly examined the cancer burden in terms of: Health-Related Quality of Life (HRQoL), work productivity and activity impairment (WPAI), stress-related comorbidities, and indirect costs in patients diagnosed with (i) any type of cancer, (ii) breast cancer, (iii) colorectal cancer, compared to controls without cancer.Materials and methods: This cross-sectional study used data from the 2017 Japan National Health and Wellness Survey (NHWS). Patient outcomes included self-reported stress-related comorbidities, HRQoL assessed by Short Form 12-item Health Survey and EuroQoL 5-dimension scale (EQ-5D), and work productivity and indirect costs assessed by WPAI questionnaire. Multivariate analysis was performed to compare outcomes across groups. An ad-hoc analysis compared respondents currently and currently not receiving prescription medication (Rx).Results: A total of 1,540 patients with any type of cancer, 254 with breast cancer, 144 with colorectal cancer were included in the analyses and compared to 28,070 controls without cancer. After adjusting for potential confounding effects patients with any type of cancer had significantly lower mental component summary scores (45.70 vs. 46.45, p = .003), physical component summary scores (48.95 vs. 50.02, p < .001) and EQ-5D index (0.77 vs. 0.79, p < .001), and significantly increased absenteeism (5.13% vs. 2.68% p < .001) compared to controls. No significant differences were detected for indirect costs. Breast cancer patients had significantly increased odds of anxiety and migraine. Colorectal cancer patients had significantly increased odds of insomnia. Patients currently receiving Rx had significantly lower HRQoL and higher WPAI than both controls and cancer patients not receiving Rx.Conclusions: Japanese cancer patients experience a significantly decreased HRQoL, increased absenteeism and higher odds ratio for stress-related comorbidities. This has implications for future policy making and Health Technology Assessment in Japan.
Assuntos
Efeitos Psicossociais da Doença , Nível de Saúde , Saúde Mental , Neoplasias/economia , Neoplasias/epidemiologia , Qualidade de Vida , Absenteísmo , Adulto , Fatores Etários , Idoso , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/economia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/economia , Comorbidade , Estudos Transversais , Eficiência , Feminino , Gastos em Saúde/estatística & dados numéricos , Inquéritos Epidemiológicos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Neoplasias/tratamento farmacológico , Desempenho Físico Funcional , Fatores Sexuais , Participação Social , Fatores Socioeconômicos , Estresse Psicológico/epidemiologiaRESUMO
Aims: As the number of cancer patients increases in Japan, and people are living longer with cancer, the need for caregivers of cancer patients is expected to increase substantially. This study intended to reveal the humanistic and economic burden among caregivers of cancer patients, and to compare it with the burden among caregivers of patients with other conditions (other caregivers) and non-caregivers.Materials and methods: This cross-sectional analysis used data from the Japan National Health and Wellness Survey 2017. Outcome measures included the Short Form 12-item Health Survey for health-related quality of life (HRQoL), EuroQol 5-dimension scale (EQ-5D) for health states utilities, Work Productivity and Activity Impairment questionnaire for the impact of health on productivity and activity, and indirect costs. Multivariate analysis was used to compare across groups, with adjustment for potential confounding effects.Results: A total of 251 caregivers of cancer patients, 1,543 other caregivers, and 27,300 non-caregivers were identified. Caregivers of cancer patients (average 48.0 years old) tended to be younger than non-caregivers (51.5) and other caregivers (54.4) and had the highest education level (57.8% completed university education). Fewer non-caregivers had stress-related comorbidities than caregivers. Non-caregivers had significantly higher EQ-5D index scores than caregivers (average 0.81 vs. 0.73 vs. 0.74). Caregivers of cancer patients had significantly lower mental component summary scores than non-caregivers (40.18 vs. 46.70), and the difference indicated a clinically meaningful decrease in HRQoL. Caregivers of cancer patients had significantly higher presenteeism (37.31% vs. 20.43%), total work productivity impairment (38.85% vs. 21.98%), and activity impairment (40.94% vs. 25.78%) than non-caregivers. Additionally, caregivers of cancer patients had significantly higher total indirect costs (36.34% vs. 20.03% of average annual income).Conclusions: These results have implications for future healthcare planning, suggesting the importance of healthcare systems in Japan to consider the substantial burden borne by caregivers of cancer patients.
Assuntos
Cuidadores/economia , Cuidadores/psicologia , Neoplasias/epidemiologia , Qualidade de Vida , Atividades Cotidianas , Adulto , Idoso , Comorbidade , Estudos Transversais , Eficiência , Feminino , Nível de Saúde , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Modelos Econométricos , Fatores Socioeconômicos , Estresse Psicológico/economia , Estresse Psicológico/epidemiologiaRESUMO
BACKGROUND: Stroke has been found to have a seasonally varying incidence; blood pressure, one of its risk factors, is influenced by humidity and temperature. The relationship between the incidence of stroke and meteorological parameters remains controversial. OBJECTIVE: We investigated whether meteorological conditions are significant risk factors for stroke, focusing on the fluctuation of weather elements that triggers the onset of stroke. METHODS: We collected ambulance transportation data recorded by emergency personnel from Gifu Prefecture. We included cases where the cause of the transportation was stroke and excluded cases of trauma. We combined these data with meteorological data as well as data on average temperature, average air pressure, and humidity provided publicly by the Japan Meteorological Agency. Our target period was from January 2012 to December 2016. RESULTS: In the 5-year target period, there were 5,501 occurrences of ambulance transportation due to stroke. A seasonal tendency was confirmed, since ambulance transportation for stroke occurred more frequently at low temperatures (p < 0.001). Temperature (odds ratio: 0.91; p < 0.001) and humidity change (odds ratio: 1.50; p = 0.016) were identified as risk factors for ambulance transportation due to stroke. An increase in temperature incurs a lower risk than a decrease (odds ratio: 0.58; p = 0.09), although there is no statistically significant difference. CONCLUSIONS: Meteorological effects on the frequency of ambulance transportation due to stroke were studied. A lower temperature and radical humidity change were identified as risk factors for ambulance transportation due to stroke, and a decrease in temperature was also associated. We speculate on the possibilities of using meteorological data to optimize the assignment of limited medical resources in medical economics.
Assuntos
Estações do Ano , Acidente Vascular Cerebral/epidemiologia , Tempo (Meteorologia) , Ambulâncias , Humanos , Umidade , Incidência , Japão/epidemiologia , Prognóstico , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Temperatura , Fatores de TempoRESUMO
BACKGROUND: Recent trends in globalization and the complexity of drug development have resulted in the possibility that expedited programs in one country may now influence drug development in another. We examined the effects of expedited programs in the United States on the development of oncology drugs in Japan. METHODS: Among oncology drugs approved in Japan between 2007 and 2016, we analyzed those that were approved in both the United States and Japan. The development period was calculated by subtracting the start date of the first clinical study or the investigational new drug application date from the drug approval date in the respective country. All data were obtained from publicly disclosed information. RESULTS: We analyzed a total of 108 approvals for oncology drugs. The difference in the development start date between the United States and Japan for drugs granted Breakthrough Therapy designation was smaller than that for drugs without this designation ( P < .01). The development period in Japan for drugs granted Breakthrough Therapy, Accelerated Approval or Fast Track designations was significantly shorter than that for drugs without these designations ( P < .05). In addition, the development period of oncology drugs in Japan tended to be significantly shorter as the number of expedited program designations increased ( P < .006 for trend). CONCLUSIONS: The characteristics and the target disease of the drug that could be eligible for expedited program(s) in the United States, which was supported by the designation, were one of the factors influencing the development of oncology drugs in Japan.
Assuntos
Antineoplásicos , Desenvolvimento de Medicamentos , Japão , Estados UnidosRESUMO
BACKGROUND: Japan has been preparing to implement a Health Technology Assessment (HTA) process in 2018. Through a 2-year pilot program implemented in 2016, the government examined the criteria for applicable products and the necessary infrastructure to review both the content and quality of the data and to conduct cost-effectiveness assessments to be incorporated into the current Japanese reimbursement and pricing scheme. A survey of the pharmaceutical industry was conducted to understand the current landscape and to identify issues and challenges of implementing HTA in Japan. METHODS: A semi-structured 19-item questionnaire was designed, and a survey was conducted via face-to-face or phone interviews. Answers were transcribed in English after the interviews and confirmed by e-mail. The survey focuses on pharmaceutical companies that develop new innovative products to be associated with the planned HTA. RESULTS: Differences between Japanese and global pharmaceutical companies were observed in terms of dedicated HTA teams in place, the use of quality of life data, and relationships with external vendors. Addressing a shortage of HTA professionals in Japan is critical to implement HTA. The survey found that list prices compared to those proposed by companies was an issue. CONCLUSIONS: Although the government decided to implement HTA for the pricing scheme in 2018, a shortage of experts and researchers remains a challenge. Findings suggest HTA should not be used solely to reduce pharmaceutical spending, as the impact by the HTA implementation will be temporary and discourage innovation.
Assuntos
Indústria Farmacêutica , Avaliação da Tecnologia Biomédica , Análise Custo-Benefício , Humanos , Japão , Avaliação de Programas e Projetos de Saúde , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: The approval of anticancer drugs in Japan has increased to meet high medical demand. To maximize the benefits of anticancer drugs, adverse drug reactions (ADRs) must be properly managed. However, in some cases, clinically significant safety issues are detected after launch, and safety-related regulatory actions (SRRAs) are implemented. OBJECTIVES: We aimed to determine the characteristics of SRRAs for anticancer drugs approved in Japan and to identify factors related to the drug development and regulatory approval process associated with the occurrence of an SRRA. METHODS: We defined an SRRA as the issuance of a 'Yellow Letter', 'Blue Letter', or an official notification by the Ministry of Health, Labor and Welfare. Anticancer drugs approved in Japan as new active ingredients from April 2004 to July 2016 were analyzed using publicly available information. The Kaplan-Meier survival curve was plotted to estimate the probability of the occurrence of an SRRA, and the Cox proportional hazards model was used to identify risk factors associated with the occurrence of an SRRA. Independent variables were selected using backward/forward stepwise selection according to Akaike's Information Criterion. RESULTS: An SRRA was implemented for 38 of 63 anticancer drugs. Approximately 70% of SRRAs occurred within 2 years after approval, and the median time between approval and the occurrence of an SRRA was 1.6 years (interquartile range 0.94-2.4). No Yellow Letter was issued during the follow-up period; however, one Blue Letter was issued for 'acute lung injury and interstitial pneumonia' for sorafenib. According to official notifications, 'clinically significant adverse reactions' was the most revised section of package inserts (62%). The probability of an SRRA at the 1-, 2- and 3-year follow-up was 15.9% (95% confidence interval [CI] 6.4-24.4%), 41.3% (95% CI 27.8-52.3%), and 56.8% (95% CI 41.8-68.0%), respectively. Monoclonal antibodies were associated with a low risk of occurrence of an SRRA (hazard ratio [HR] 0.29, p = 0.019), while the large number of patients in pivotal studies (per 100 patients) was associated with a high risk of occurrence (HR 1.07, p = 0.012). CONCLUSIONS: The high-risk period for the occurrence of an SRRA for anticancer drugs in Japan was within 2 years after approval. Among the factors related to the drug development and regulatory approval process, anticancer drugs in the form of non-monoclonal antibodies, and whose pivotal studies included a large number of patients, were more likely to be associated with an SRRA. Postmarketing follow-up should therefore be carefully performed, especially in the first 2 years after approval and for non-monoclonal antibody anticancer drugs. Moreover, postmarketing follow-up is crucial, even if large-scale pivotal studies for regulatory approval have already been performed.