Bruce Crawford

Background: Regimen simplification to 2-drug antiretroviral therapy (2-ART) may address potential tolerability issues, increase adherence, and reduce toxicity and potential drug-drug-interactions among people living with HIV-1 (PLWH). However, real-world treatment patterns and characteristics of 2-ART users are unclear. Methods: This retrospective observational cohort study employed a large-scale medical claim database of Japanese hospitals to extract data on 4,293 PLWH aged ≥18 years with diagnosis of HIV and treated with any ART regimens between April 2008 and April 2019. A 2-ART cohort was compared with a 3-drug antiretroviral therapy (3-ART) cohort in terms of population characteristics, comorbid conditions, and treatment patterns. Treatment switching rates were calculated for each cohort followed by sensitivity analysis to confirm the robustness of the findings. Results: There were 94 individuals identified in the 2-ART cohort. Compared to the standard 3-ART cohort (n = 3,993), the 2-ART cohort was older (median age 53 [IQR 44–64] vs 42 years [IQR 35–50]), with a lower proportion of males (87.2% vs 93.8%), higher Charlson Comorbidity Index (CCI) (median score 6 [IQR 5–8] vs 5 [IQR 4–6]), more co-medications (median 6 [IQR 4–11] vs 3 [IQR 2–7]), and a higher percentage of AIDS-defining conditions (66.0% vs 42.8%). The most common 2-ART were protease inhibitor (PI) + integrase strand transfer inhibitor (INSTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) + INSTI (33.0% and 31.9%, respectively). Overall, most of the regimens were nucleoside reverse transcriptase inhibitor (NRTI)-sparing (71.3%), with a decreasing trend over time (76.2% to 70.2%). ART regimen switch occurred more often in the 2-ART cohort than in the 3-ART cohort (33.0% vs 21.2%). Conclusion: The profiles of individuals on 2-ART in Japan were demonstrated to be complex. Most were treated with NRTI-sparing regimens which may reflect an effort to reduce treatment-related toxicities.

This study explored the burden associated with stem cell mobilization, with or without cyclophosphamide (CPA), in patients who intended to receive autologous stem cell transplantation (ASCT) for multiple myeloma (MM). A Japanese health care claims database (MDV) was used to analyze the health care resource utilization patterns and medical cost between 2013 and 2016 (pre-plerixafor launch). The patients were further categorized into groups who received granulocyte-colony stimulating factor (G-CSF) alone or G-CSF + CPA group and analyzed in both mobilization and ASCT phases of treatment. Overall, there were more MM patients who were treated with G-CSF + CPA combination therapy than G-CSF alone. Length-of-stay was 1.6 times longer in the combination group during the mobilization phase. A reverse trend was observed during the ASCT phase. Direct cost was approximately 1.2 million yen during the mobilization phase and 2.3 million yen during the ASCT phase, with hospitalization basic fee accounting for the highest proportion in both groups and phases. A substantial amount of healthcare resource and cost was consumed in both phases. This study may serve as a basic reference for further health technology assessment of new medicines such as plerixafor. Further investigation of differences between treatment groups is warranted.

Introduction Reliable quality of life (QoL) measures and utility values are needed for patients with type 2 diabetes mellitus (T2DM) with a variety of comorbid conditions to help facilitate cost-effectiveness modeling. This study aimed to evaluate the Diabetes Treatment-Related Quality of Life (DTR-QOL) and EuroQol 5-dimension 5-level (EQ-5D-5L) questionnaires in patients with T2DM with and without diabetes complications and comorbidities in Japan. Methods This was an observational survey study involving 1000 patients with T2DM, at least 20 years old, receiving treatment at Nara University Hospital or Takamura Internal Medicine Clinic in Japan. Patients completed the DTR-QOL and EQ-5D-5L questionnaires and clinicians completed an accompanying case report form. The DTR-QOL and EQ-5D-5L are scored on a scale of 0–100 and 0–1, with 100 and 1 representing the best possible scores, respectively. Results Out of 1000 recruited patients, 978 were included in the final analysis. Patients reported an average EQ-5D-5L value of 0.92 ± 0.11. Utility values corresponded to the degree of severity of health conditions while few differences were observed when stratified by the HbA1c 7% threshold, age, or BMI level, nor did the values correspond to the degree of clinical risk factors. Patients reported an average total DTR-QOL score of 79.26 ± 13.26. The DTR-QOL was sensitive to detect differences in patients with T2DM with a variety of complications and comorbidities, risk factors, and treatments. Conclusion This is the largest study to report QOL values for patients with diabetes in Japan and the first to include a variety of comorbid diabetic conditions. These findings may be useful for cost-effectiveness modeling of patients with T2DM in Japan.

Aims: To present the development of the International Consultation on Incontinence Questionnaire‐underactive bladder (ICIQ‐UAB) as the first patient reported outcome measure for the assessment of the symptoms and impact on the health‐related quality of life of UAB developed in‐line with the Food and Drug Administration Guidance for Industry.Methods: Draft items were developed following 44 semi‐structured concept elicitation interviews in the UK and refined using 36 cognitive interviews. A pilot study was designed to assess the draft ICIQ‐UAB's initial psychometric properties with 54 patients recruited from European hospitals. Further concept elicitation interviews were also carried out with 11 patients in the US and 10 patients in Japan. All participants had a prior urodynamic diagnosis of detrusor underactivity.Results: The cognitive interviews confirmed the initial items to be understood and interpreted as intended. Pilot testing showed that both internal consistency (Cronbach's α ≥ 0.85) and test‐retest reliability (stable patients; intraclass correlation coefficient ≥ 0.88) were high. The interviews in the US and Japan elicited symptoms and impacts that support previous findings in the UK and provided further insight into the experiences of patients in those countries. The developmental ICIQ‐UAB was refined using the evidence from all substudies.Conclusions: The validity and reliability of the ICIQ‐UAB were supported in a pilot study setting and the wider cultural applicability by the additional interviews in the US and Japan. Following further validation in future clinical trials, the developmental ICIQ‐UAB is envisaged as an important tool for the monitoring of future UAB treatment strategies.

The objectives of this study were to develop a conceptual framework for the diabetes treatment-related quality of life (DTR-QOL) and validate the new structure of the DTR-QOL.

Background: Neuropathic pain (NP) is a complex, chronic pain state initiated by a primary lesion or dysfunction of the nervous system and presents as a variety of symptoms across multiple disease states.Objective: To develop a patient‐centred conceptual model of symptoms and impacts in subjects with diabetic peripheral neuropathy (DPN) or post‐herpetic neuralgia (PHN) that can inform the measurement strategy in clinical trials.Method: Thirty subjects with DPN or PHN participated in in‐person interviews which were performed until saturation was achieved. Transcripts were analysed in ATLAS.ti.Results: Interviews were completed with DPN subjects (United States, n = 10; Japan, n = 10) and PHN subjects (United States, n = 5; Japan, n = 5). Numbness and tingling were frequently reported symptoms in the DPN population while itchiness and hypersensitivity were predominant in PHN. Both populations experienced burning and ache/soreness with similar frequency. DPN subjects experienced pain primarily in their lower extremity (eg feet, ankles), while PHN subjects experienced pain primarily in the chest and back. Impacts reported by DPN subjects included difficulty walking, sleep disturbance and climbing stairs. Impacts in PHN subjects included sleep disturbance, avoidance of physical contact, being angry/frustrated and being sad/depressed. Overall, concepts in Japan were not qualitatively different from the United States. Conceptual models of NP were generated based on the concepts elicited.Conclusions: This research highlights core concepts to measure from the patient's perspective. Moreover, it enables the assessment of existing measures, the possible modification of these measures, or if a new NP measure with improved sensitivity and responsiveness is merited.

Aim: To evaluate the epidemiology and real-world treatment patterns associated with lipid-modifying therapies (LMTs) among groups of Japanese patients with familial hypercholesterolemia (FH). Methods: A retrospective observational study was conducted using an electronic hospital-based administrative claims database and electronic medical records. Patients with existing diagnosis of FH (FH-D) and patients with suspected FH (FH-S) defined by low-density lipoprotein cholesterol (LDL-C) >= 190 mg/dL were included, and medical records of hospitals across Japan were analyzed to assess the diagnostic status, management of LDL-C levels, and treatment patterns. Results: Among the 3,495 patients who met the inclusion criteria, 193 patients were FH-D and 3,339 patients were FH-S. Among them, 83.5% had not achieved the LDL-C of = 100 mg/dL. Conclusions: Treatment and management of LDL-C in Japanese FH patients remain suboptimal. The results suggest that FH is underdiagnosed in real-world, routine clinical practice in Japan. There is an urgent need to improve the diagnostic rate of FH and to provide the appropriate therapy to achieve the recommended LDL-C levels of < 100 mg/dL or a more than 50% reduction for patients with FH in Japan.

Background: Patient-reported outcomes (PRO) obtained through routine medical care may identify patients’ day-to-day burden and help tackle the disease from the patients’ perspective. However, there is a paucity of information regarding the availability of PRO data and PRO tools for rheumatoid arthritis (RA) in Japan. Objective: We reviewed the literature on PRO data availability and to identify PRO measures implemented in Japan for RA patients. Method: We conducted a systematic literature review using ICHUSHI and the PubMed databases on PRO measures for RA published from January 2011 to August 2015 in Japan. Results: After removing duplicates, 2423 manuscripts were found. From these, 100 manuscripts were included for review and analysis. We found 29 PRO tools that were used to assess various domains of health such as general well-being, pain, functionality, and fatigue. More than 90% of the studies utilized PRO tools for research purpose. Only one study reported PRO tool implementation in the routine medical care. Conclusion: The importance of PROs is recognized in Japan. PRO tools varied significantly and were mostly used for research purposes, while reports on the use of PRO measures in routine medical care were limited. Despite the awareness of PROs in the research community, unmet needs remain among RA patients in Japan. Further work is needed to investigate ways in which PROs can better reflect these unmet needs and be utilized in routine medical care.