Assessing Definitions and Incentives Adopted for Innovation for Pharmaceutical Products in Five High-Income Countries: A Systematic Literature Review.

BACKGROUND: The concept of health care innovation varies across organizations and countries. Harmonizing the definitions of innovation can augment the discovery of new therapies, minimize costs, and streamline drug development and approval processes. A systematic literature review (SLR) was conducted to gather insights surrounding different elements of innovation in the USA, the UK, France, Germany, and Japan. The SLR identified studies that have defined innovation and captured the types of incentives provided to promote innovation. METHODS: The MEDLINE, Embase, and EconLit databases were searched via the OVID SP platform on October 22, 2020. A secondary desk search literature review was performed to identify additional information of interest in regional languages: French, German, and Japanese. All the relevant literature in English was screened using the Linguamatics natural language processing (NLP) tool, except for articles from EconLit, which were screened manually using structured search strategies. Articles that describe a definition of innovation or refer to a definition of innovation published were included. All full-text articles were reviewed manually, and two reviewers independently screened the full texts for eligibility. RESULTS: After screening, 90 articles were considered to meet the SLR objectives. The most common dimension of innovation identified was therapeutic benefit as a measure of innovation, followed by newness and novelty aspects of innovations. Incentives around exclusivities were found to be the most prevalent in the data set, followed by rewards and premiums. Among the different therapy areas, the largest number of innovations was targeted at oncology. CONCLUSIONS: This SLR highlights the lack of a unified definition of innovation among regulatory authorities and health technology assessment bodies in five countries, and variation in the types of incentives associated with innovation. The targeted countries cover different dimensions of definition and incentives of innovation at varying levels, with a few focused on specific therapy areas. Harmonization and consensus for innovation would be needed across countries because drug development is a global undertaking. This SLR envisages a more holistic approach to evaluation, wherein the value provided to patients and health systems is accounted for. The results of this SLR will help to promote broader discussion among different stakeholders and decision makers across countries to identify gaps in policies and develop sustainable strategies to promote innovation for pharmaceutical products.

Characteristics of Japanese patients with non-dialysis-dependent chronic kidney disease initiating treatment for anemia: a retrospective real-world database study.

OBJECTIVE: Anemia is a common complication of chronic kidney disease (CKD). The aim of this study was to evaluate hemoglobin levels at the initiation of erythropoiesis stimulating agent (ESA) therapy in patients with non-dialysis-dependent CKD (NDD-CKD) and anemia using a large-scale administrative database in Japan. METHODS: The longitudinal data of adult patients who initiated ESA therapy between April 2008 and December 2018 were extracted from a hospital-based administrative database. The primary outcome was hemoglobin level at the initiation of ESA therapy, whereas the exploratory outcome was hemoglobin level recorded 6 months after the onset of the ESA therapy. RESULTS: A total of 4939 patients were included in the primary analysis. The mean hemoglobin level at the initiation of ESA therapy was 9.1 g/dL, which was lower than the level (11 g/dL) recommended for the initiation of treatment by the current Japanese treatment guidelines. Moreover, 42.1% and 15.0% of the patients had hemoglobin levels <9.0 and <8.0 g/dL, respectively, at the initiation of ESA therapy. In 2964 patients for whom hemoglobin levels at 6 months after the initiation of ESA therapy were available, the mean hemoglobin level increased to 10.3 g/dL, and 61.9% and 31.1% of these patients had hemoglobin levels ≥10.0 and ≥11.0 g/dL, respectively. CONCLUSION: This real-world database study revealed that hemoglobin levels at the initiation of ESA therapy in new users of ESA were lower than those recommended by treatment guidelines in Japan.

Cost-Effectiveness Analysis of the Treatment Strategies with or without Opioid Medications in Surgery-Eligible Patients with Osteoarthritis in Japan.

AIM: The aim of this study was to evaluate the cost effectiveness of treatment strategies without opioid medications (non-opioid treatment strategy) versus strategies with opioid medications (opioid treatment strategy) among surgery-eligible patients with osteoarthritis (OA) of the knee or hip in Japan. MATERIALS AND METHODS: We built a Markov cohort model to evaluate outcomes for the treatment strategies in surgery-eligible patients aged ≥ 65 years with OA of the knee or hip in Japan. The opioid treatment strategy as an intervention includes a health state with opioid medication in the treatment pathway. On the other hand, for the non-opioid treatment strategy, there is no health state with opioid medication. A targeted literature review and database analysis were conducted to identify and define the values of the variables included in the model. The time horizon was set to 30 years, and a 2% discount was applied for cost and quality-adjusted life-years (QALYs). Sensitivity analysis and scenario analysis were performed in the model. The outcomes were QALYs and the incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case analysis, the non-opioid treatment strategy was dominant over the opioid treatment strategy and associated with an incremental cost and QALYs of - 53,878 JPY (- 499 USD) and 0.03 QALYs, respectively, in patients with knee OA, and - 54,129 JPY (- 502 USD) and 0.02 QALYs, respectively, in patients with hip OA. One-way sensitivity analysis showed the ICER was most sensitive to the QALY for opioid monotherapy. Probabilistic sensitivity analyses showed a high degree of uncertainty associated with the results. LIMITATIONS: Study limitations included assumptions related to transition probabilities of the health states, and a lack of Japanese-specific data for transition probabilities, incidence of adverse events and utility values. CONCLUSIONS: This study suggests that the non-opioid treatment strategy is cost effective compared with the opioid treatment strategy in the management of surgery-eligible patients with OA of the knee or hip. However, this final conclusion may not be accurate as the methodology is heavily reliant on assumptions.

Investigation of Factors Considered by Health Technology Assessment Agencies in Eight Countries.

BACKGROUND: Health technology assessment (HTA) organizations play a crucial role in optimizing healthcare resources, but the factors influencing decision making vary by country. OBJECTIVE: HTAs of cancer and hepatitis C drugs were evaluated across developed countries to understand differences in decision processes and criteria. METHODS: The HTA organizations evaluated are from France, Germany, Italy, Spain, the United Kingdom (UK), Australia, Canada and Japan. Economic evaluation types and 28 factors in the following categories were evaluated: clinical uncertainties/issues; disease/population/treatment consideration factors including National Institute for Health and Care Excellence's (NICE) special circumstances factors (e.g. end-of-life and innovation); and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) additional value elements. Qualitative and correspondence analyses were conducted to assess the differences across organizations. RESULTS: Incremental cost-effectiveness ratio (ICER) using quality-adjusted life-year (QALY) was evaluated in Canada, the UK, Australia and Japan. The highest observed clinical uncertainties were clinical benefits and comparator. For cancer drugs, correspondence analysis showed France, Australia, Canada and the UK to have common attributes observed, such as unmet needs and stakeholder persuasion. In addition, the UK reported end-of-life, issues around current treatment and innovation, whereas Germany reported manageable/insignificant adverse events more frequently. Finally, fear of contagion, equity and scientific spillover value elements were only observed in Australia. CONCLUSION: Although clinical factors play a predominant role in the decision to reimburse medicine, HTA organizations consider additional aspects as well. If the methodology of HTA was clearly outlined, there would be more transparency in HTA systems leading to better understanding amongst stakeholders about decision making.

Cross-sectional survey in patients with type 1 and type 2 diabetes to understand mealtime insulin unmet needs in Japan: The MINUTES-J study.

AIMS: This study was conducted to evaluate existing burden and unmet needs related to mealtime insulin (MTI) injection timing among adult Japanese patients with type 1 (T1D) and type 2 (T2D) diabetes. It also aimed to evaluate if a novel MTI could reduce this burden. METHODS: This study comprised of a qualitative pilot study facilitating development of an online survey; followed by an online quantitative survey involving T1D, young T2D (yT2D) and elderly T2D (eT2D) patients to assess burden of current MTI timings in Japan. RESULTS: Overall, 38% patients (amongst T1D, yT2D and eT2D groups) reported injecting MTI just before start or during meal in the past month. Experiencing lower glucose level/hypoglycemic condition before the meal and forgetting were the main reasons for injecting during/after meal in T1D and T2D patients respectively. Patients reported moderate-to-severe burden in multiple aspects of their lives, associated with current MTI timing. Most patients perceived that this burden would remain the same if a faster acting MTI was available. CONCLUSIONS: Substantial burden reported by Japanese patients regarding the current MTI timings suggests the need for new MTI products that could achieve optimal post-prandial glucose control at different timings to meet patients' needs in Japan.

Evaluation of the Optimal Position for Vedolizumab in the Japanese Treatment Paradigm for Ulcerative Colitis Using Markov Modeling.

Background: This analysis assessed the optimal position of vedolizumab for Japanese patients with ulcerative colitis. Methods: A Markov model was used to evaluate the performance of 4 treatment algorithms of vedolizumab position: after azathioprine (Algorithm 1); after tacrolimus/cytapheresis (Algorithm 2); after a first anti-tumor necrosis factor alpha (anti-TNFα) (Algorithm 3); and after a second anti-TNFα before colectomy (Algorithm 4). Results: Algorithm 1 was the dominant strategy, with an incremental benefit over the other algorithms of 0.028-0.031 quality-adjusted life years. Conclusions: This simulation predicts that introducing vedolizumab immediately after a thiopurine and before other therapies will provide most benefit.

Erratum: Evaluation of the Optimal Position for Vedolizumab in the Japanese Treatment Paradigm for Ulcerative Colitis Using Markov Modeling.

[This corrects the article DOI: 10.1093/crocol/otaa017.].

Burden of atopic dermatitis in Japanese adults: Analysis of data from the 2013 National Health and Wellness Survey.

Atopic dermatitis is a chronic inflammatory skin disease. The objective of this study was to characterize the burden of atopic dermatitis in Japanese adult patients relative to the general population. Japanese adults (≥18 years) with a self-reported diagnosis of atopic dermatitis and adult controls without atopic dermatitis/eczema/dermatitis were identified from the 2013 Japan National Health and Wellness Survey. Atopic dermatitis patients were propensity-score matched with non-atopic dermatitis controls (1:2 ratio) on demographic variables. Patient-reported outcome data on comorbidities, mood and sleep disorders, health-related quality of life, work productivity and activity impairment, and health-care resource utilization were analyzed in atopic dermatitis patients and matched controls. A total of 638 Japanese adult patients with atopic dermatitis were identified, of whom 290 (45.5%) rated their disease as "moderate/severe" and 348 (54.5%) as "mild". The analysis cohort comprised 634 atopic dermatitis patients and 1268 matched controls. Atopic dermatitis patients reported a significantly higher prevalence of arthritis, asthma, nasal allergies/hay fever, anxiety, depression and sleep disorders compared with controls (all P < 0.001). Atopic dermatitis patients also reported a significantly poorer health-related quality of life, higher overall work and activity impairment, and higher health-care resource utilization (all P < 0.001). Self-rated disease severity was not associated with disease burden, except for a significantly higher overall work and activity impairment. In conclusion, Japanese adult patients with atopic dermatitis reported a substantial disease burden relative to adults without atopic dermatitis, suggesting an unmet need for effective strategies targeting disease management.