Review of real-world evidence studies in type 2 diabetes mellitus: Lack of good practices.

OBJECTIVES: Unlike randomized controlled trials, lack of methodological rigor is a concern about real-world evidence (RWE) studies. The objective of this study was to characterize methodological practices of studies collecting pharmacoeconomic data in a real-world setting for the management of type 2 diabetes mellitus (T2DM). METHODS: A systematic literature review was performed using the PICO framework: population consisted of T2DM patients, interventions and comparators were any intervention for T2DM care or absence of intervention, and outcomes were resource utilization, productivity loss or utility. Only RWE studies were included, defined as studies that were not clinical trials and that collected de novo data (no retrospective analysis). RESULTS: The literature search identified 1,158 potentially relevant studies, among which sixty were included in the literature review. Many studies showed a lack of transparency by not mentioning the source for outcome and exposure measurement, source for patient selection, number of study sites, recruitment duration, sample size calculation, sampling method, missing data, approbation by an ethics committee, obtaining patient's consent, conflicts of interest, and funding. A significant proportion of studies had poor quality scores and was at high risk of bias. CONCLUSIONS: RWE from T2DM studies lacks transparency and credibility. There is a need for good procedural practices that can increase confidence in RWE studies. Standardized methodologies specifically adapted for RWE studies collecting pharmacoeconomic data for the management of T2DM could help future reimbursement decision making in this major public health problem.

Real-world evidence: a practical toolbox for collecting health state utilities.

Health state utilities (HSU) data collected in real-world evidence studies are at risk of bias. Although numerous guidance documents are available, practical advice to avoid bias in HSU studies is limited. Thus, the objective of this article was to develop a concise toolbox intended for investigators seeking to collect HSU in a real-world setting. The proposed toolbox builds on existing guidance and provides practical steps to help investigators perform good quality research. The toolbox aims at increasing the credibility of HSU data for future reimbursement decision making.

The Impact of Hypoglycemia on Productivity Loss and Utility in Patients With Type 2 Diabetes Treated With Insulin in Real-world Canadian Practice: Protocol for a Prospective Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) imposes a substantial burden owing to its increasing prevalence and life-threatening complications. In patients who do not achieve glycemic targets with oral antidiabetic drugs, the initiation of insulin is recommended. However, a serious concern regarding insulin is drug-induced hypoglycemia. Hypoglycemia is known to affect quality of life and the use of health care resources. However, health economics and outcomes research (HEOR) data for economic modelling are limited, particularly regarding utility values and productivity losses. OBJECTIVE: This real-world prospective study aims to assess the impact of hypoglycemia on productivity and utility in insulin-treated adults with T2DM from Ontario and Quebec, Canada. METHODS: This noninterventional, multicenter, 3-month prospective study will recruit patients from 4 medical clinics and 2 endocrinology or diabetes clinics. Patients will be identified using appointment lists and enrolled through consecutive sampling during routinely scheduled consultations. To be eligible, patients must be aged ≥18 years, diagnosed with T2DM, and treated with insulin. Utility and productivity will be measured using the EQ-5D-5L questionnaire and Institute for Medical Technology Assessment Productivity Cost Questionnaire, respectively. Questionnaires will be completed 4, 8, and 12 weeks after recruitment. Generalized estimating equation models will be used to investigate productivity losses and utility decrements associated with incident hypoglycemic events while controlling for individual patient characteristics. A total of 500 patients will be enrolled to ensure the precision of HEOR estimates. RESULTS: This study is designed to fill a gap in the Canadian evidence on the impact of hypoglycemia on HEOR outcomes. More specifically, it will generate productivity and utility inputs for the economic modeling of T2DM. CONCLUSIONS: Insulin therapy is expensive, and hypoglycemia is a significant component of economic evaluation. Robust HEOR data may help health technology assessment agencies in future reimbursement decision-making. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/35461.

Frailty in HIV infected people: a new risk factor for bone mineral density loss.

OBJECTIVE: The study aims to assess the association between bone mineral density (BMD) and frailty in a cohort of HIV-infected patients. DESIGN: A cross-sectional study in an HIV outpatient unit where nearly 1000 patients are monitored. METHODS: Study participants undergoing bone densitometry were proposed an evaluation of frailty using criteria of the Cardiovascular Health Study (CHS) and the Study of Osteoporotic Fractures (SOF). Frailty markers were weight-loss, self-reported exhaustion, physical activity, grip strength, chair stands, and slow gait. Patients' characteristics were collected from an electronic medical record. Associations of frailty with BMD and osteoporosis were tested using multivariate linear and logit regression models, respectively. RESULTS: In total, 175 HIV-infected patients, 121 (69.14%) men, were analyzed. Prevalence of frailty markers, osteopenia, and osteoporosis were comparable among sexes. Despite a younger age, spinal and femoral neck BMD were lower in women (P < 0.05). Linear regression model adjusting by age, duration of HIV follow-up, BMI, smoking status, osteoarthritis, osteoporosis treatment, and the age at menopause showed a negative association of spinal and femoral BMD with frailty according to SOF criteria in women (P < 0.05). In men, SOF-defined frailty was associated with osteoporosis (odds ratio 28.79; 95% confidence interval 2.15-386.4) in a model adjusting for age, duration of HIV follow-up, CD4 nadir, CD4 T-cell count, tobacco consumption, exposure to tenofovir (TDF) and protease inhibitors. No significant associations were found between BMD and CHS-defined frailty. CONCLUSION: Our study shows that frailty according to SOF criteria is associated with low spinal BMD values in female and osteoporosis in male HIV-infected patients.

Impact of antiretroviral treatment on the tropism of HIV-1 plasma virus populations.

OBJECTIVE: To study the impact of antiretroviral therapy on the tropism of plasma HIV-1 virus populations during treatment response and virological escape. DESIGN: To investigate whether the selective pressure exerted by antiretroviral treatment influences the tropism of the plasma virus populations, we retrospectively determined the co-receptor usage of viruses present in plasma samples obtained before and at varying intervals after starting antiviral therapy. METHODS: The co-receptor usage of plasma virus was determined using our recently published tropism recombinant test (V. Trouplin et al., J Virol, 2001; 75:251-259). This assay relies on virus production by homologous recombination between a plasmid encoding the entire HIV genome except for a deletion of the major tropism determinant, and a polymerase chain reaction (PCR) product spanning this region and the adjoining flanking sequences, obtained by reverse transcriptase (RT)-PCR amplification of viral RNA from the patient's plasma. RESULTS: Twenty-four of the 32 patients analysed harboured exclusively R5 virus in plasma before the initiation of treatment, whereas eight had mixed R5/X4 virus populations. In four of these eight patients, all of whom initially responded to treatment, the persistence of R5 virus in plasma was observed, whereas the X4 component of the virus population became undetectable. The suppression of the X4 virus component was a transient phenomenon and variants able to use CXCR4 re-emerged after a variable delay. CONCLUSIONS: The impact of therapy on virus populations differs according to virus tropism. Differences in target cell populations, tissue distribution and replication characteristics between R5 and X4 viruses could explain the preferential suppression of X4 virus.