Pradana Soewondo

Observational studies: going beyond the boundaries of randomized controlled trials

The term observational study describes a wide range of study designs including prospective and retrospective cohort studies, case-control studies, and cross-sectional studies, a defining feature of which is that any intervention studied is determined by clinical practice and not the protocol. Data from large, prospective observational studies provide information about the safety and efficacy of medicines in daily clinical use. Such observational studies are generally carried out once a medicine has received approval from regulatory agencies. Observational trials have inherent limitations in terms of their susceptibility to bias and confounding, restricting their ability to define causality. However, their strengths include that they reflect daily clinical practice more closely than randomized controlled trials (RCTs), both in terms of the heterogeneous patient populations that are included, and the medical interventions that they receive. Therefore, observational trials can provide clinically relevant information that is not necessarily provided by RCTs. Given the limitations of an observational study approach, it is important to optimize their study design to maximize their validity, and thus, in particular, known causes of bias and confounding should be measured. Medical investigators, health authorities, and the pharmaceutical industry all have important roles to play in designing, approving, and performing observational studies.

Improvements in quality of life associated with insulin analogue therapies in people with type 2 diabetes: Results from the A1chieve observational study

AIMS To determine the effects on quality of life after starting insulin with, or switching to, insulin analogue therapies in the 24-week, prospective, non-interventional, observational A(1)chieve study conducted across four continents in people with type 2 diabetes. METHODS Health-related quality of life (HRQoL) was assessed at baseline and at 24 weeks by the validated EQ-5D questionnaire (visual analogue score [VAS] and five dimensions) in 66,726 people who had started using basal insulin detemir, mealtime insulin aspart (with or without a basal insulin) or biphasic insulin aspart 30. RESULTS For the overall cohort, reported HRQoL increased significantly by 13.8 points from 63.4 points at baseline to 77.2 points at 24 weeks (p<0.001) (scale 1-100, 100=best health imaginable). Beginning or changing insulin was associated with a significant increase in HRQoL score (+15.0 points and +11.1 points, respectively), resulting in a similar score at 24 weeks in the two populations (77.8 and 75.9 points). Reported HRQoL also increased statistically significantly in people administering any insulin analogue regimen and across all regions, although there were some marked regional differences in reported HRQoL at baseline. CONCLUSION Compared with baseline scores, beginning insulin with, or switching to, insulin analogue therapies are associated with increased HRQoL.

Challenges in diabetes management in Indonesia: a literature review

Background and objectivesThe expanding diabetes epidemic worldwide could have potentially devastating effects on the development of healthcare systems and economies in emerging countries, both in terms of direct health care costs and loss of working time and disability. This study aims to review evidence on the burden, expenditure, complications, treatment, and outcomes of diabetes in Indonesia and its implications on the current health system developments.MethodsWe conducted a comprehensive literature review together with a review of unpublished data from the Ministry of Health and a public health insurer (Askes). Studies presenting evidence on prevalence, incidence, mortality, costs, complications and cost of complications, treatment, and outcomes were included in the analysis.ResultsA limited number of international, national and local studies on the burden and cost of diabetes in Indonesia were identified. National survey data suggests that in 2007 the prevalence of diabetes was 5.7%, of which more than 70% of cases were undiagnosed. This estimate hides large intracountry variation. There was very limited data available on direct costs and no data on indirect costs. The most commonly-identified complication was diabetic neuropathy.DiscussionThere were a number of limitations in the data retrieved including the paucity of data representative at the national level, lack of a clear reference date, lack of data from primary care, and lack of data from certain regions of the country.ConclusionsIf left unaddressed, the growing prevalence of diabetes in the country will pose a tremendous challenge to the Indonesian healthcare system, particularly in view of the Government’s 2010 mandate to achieve universal health coverage by 2014. Essential steps to address this issue would include: placing diabetes and non-communicable diseases high on the Government agenda and creating a national plan; identifying disparities and priority areas for Indonesia; developing a framework for coordinated actions between all relevant stakeholders.

The Diabcare-Asia 1998 Study -Outcomes on Control and Complications in Type 1 and Type 2 Diabetic Patients

Summary The aim of this study was to describe the glycaemic and metabolic control and diabetes-related complications in type 1 and type 2 Asian patients. Methods: Data of diabetes patients from 230 diabetes centres in 12 Asian regions were collected on a retrospective-prospective basis through review of medical records, interview and laboratory assessments. Analysis of glycated haemoglobin (HbA1c) was carried out in central laboratories appointed by Bio-Rad. The data collection case record forms were scanned electronically. Results: 22177 patients with valid data made up the analysis population. Among patients with type 1 and type 2 diabetes, there was a higher proportion of women than men (53% vs. 47% for type 1 patients and 56% vs. 44% for type 2 diabetes). Hypertension (61%) and overweight (40% with BMI >25 kg/m2) were common in type 2 patients. Dyslipidaemia was also present in at least half of both types of patients. Control of glycaemia (mean HbA1c and fasting blood glucose [FBG]) was poor in type 1 (9.9 ± 2.5%; 10.2 ± 5.2 mmol/l) and type 2 patients (8.5 ± 2.0%; 8.9 ± 3.4 mmol/l). Glycaemia in the majority of both types of patients fell short of those stipulated by various guidelines. In type 2 patients, glycaemia deteriorated (HbA1c > 7.5%, FBG > 7.0mmol/l) with duration of diabetes > 7 years. Both types of diabetes appear to share a similar high prevalence of complications of cataract, retinopathy and neuropathy, although the prevalence of cataract (27%) and neuropathy (35%) was higher in type 2 diabetes. Screening for microalbuminuria was not common. Conclusions: The inadequate metabolic and hypertension control, especially in type 2 patients, needs to be addressed.

Addressing the burden of type 2 diabetes and cardiovascular disease through the management of postprandial hyperglycaemia: an Asian-Pacific perspective and expert recommendations

The world is facing an epidemic of cardiovascular disease (CVD) and type 2 diabetes, with populations in low- to middle-income countries, including many in the Asia Pacific (AP) region, being disproportionately affected. Emerging data identify postprandial hyperglycaemia (PPHG) as an important predictor of CVD, and several professional bodies, including the International Diabetes Federation, have issued guidelines on the management of PPHG in type 2 diabetes. Guidance on how international recommendations could be implemented in Asian populations is currently lacking. Therefore, a panel of experts from the AP region convened to consider the current status of PPHG and CVD in the region, and to develop recommendations for clinical practice. The group concluded that improved awareness of the impact of PPHG on CVD risk, among clinicians and the general public, and more widespread use of routine screening for PPHG, using oral glucose tolerance testing in those without recognised diabetes, are required. Additionally, frequent meal-based testing and effective PPHG management are essential to the management of IGT and type 2 diabetes.

Awareness, agreement, adoption and adherence to type 2 diabetes mellitus guidelines: a survey of Indonesian primary care physicians.

BackgroundTo assess the degree of awareness, agreement, adoption and adherence of physicians in Indonesia to type 2 diabetes mellitus guidelines, and their association with characteristics of the responders.MethodsQuestionnaire survey among General Practitioners (GPs) attending the Indonesian Association of Family Practitioners annual conference in November 2012. The proportion of GPs who were aware of, agreed with, adopted and adhered to the seven recommendations in the guidelines (screening for diabetes, diagnosis, lifestyle modification, use of sulfonylurea, target blood glucose, target blood pressure and use of statin) were calculated in the total number of responders.ResultsOf the 399 GPs participating, 383 (89%) were aware of the existence of Indonesian type 2 diabetes guidelines. Awareness for each recommendation varied from 66 to 91%. The recommendation to use a random blood glucose test for diagnosing patients with classic diabetes symptoms had the least awareness (265/399, 66%) and least agreement (163/399, 41%). The recommendation on statin use was the least adopted (192/399, 48%), while the least adherence (7/399, 2%) was found for the recommendation on screening for diabetes for patients with risk factors. Years of practice experience and proportion of diabetes patients seen in their practice were independently related with adherence to statin prescription.ConclusionsHigh awareness of the Indonesian type 2 diabetes guideline does not necessary lead to adoption or adherence to recommendations important for outcomes and quality of care. The awareness-to-adherence model helps in identifying barriers for the use of guidelines.

Switching from biphasic human insulin 30 to biphasic insulin aspart 30 in type 2 diabetes is associated with improved glycaemic control and a positive safety profile: Results from the A1chieve study

AIMS This A1chieve® study subgroup analysis examined clinical safety and effectiveness of biphasic insulin aspart 30 (BIAsp30) ±OGLDs in 6323 individuals with T2D, switching from biphasic human insulin 30 (BHI30) ±OGLDs. METHODS A1chieve was a 24-week, international, prospective, observational, multi-centre, open-label study in individuals with T2D starting treatment with BIAsp30, insulin detemir or insulin aspart as part of routine clinical care. RESULTS Mean baseline (SD) dose BHI was 0.56 (0.25) IU/kg. BIAsp30 was initiated at 0.57 (0.25) U/kg; the daily dose was 0.62 (0.28)U/kg by Week 24. Switching from BHI30 to BIAsp30 was associated with significant mean reduction in HbA1c of 1.7% [-18 mmol/mol] (1.6) from a baseline of 9.1% [76 mmol/mol] (p<0.001); FPG and PPG were also significantly reduced (p<0.001). Major hypoglycaemic episodes decreased from 0.69 events/patient/year at baseline to 0.03 events/patient/year at Week 24. Minor hypoglycaemia decreased from 5.31 to 2.04 events/patient/year from baseline to study-end. Five serious adverse drug reactions (hypoglycaemia) were reported by five individuals (0.1%). Mean bodyweight increased by 0.1 (3.3)kg from baseline to 24 weeks. Improved self-reported quality of life was observed. CONCLUSION Switching from BHI30 to BIAsp30 in individuals with T2D is associated with improvement in glycaemic control and reduced rates of hypoglycaemia, without tolerability or safety issues.

Helminths, hygiene hypothesis and type 2 diabetes.

Worldwide, there is little overlap between the prevalence of soil‐transmitted helminths and type 2 diabetes (T2D). Helminth‐induced type 2 immune responses and immune regulatory network might modulate the obesity‐induced activation of inflammatory pathways that are associated with the development of insulin resistance, a strong predictor of the development of T2D. However, other factors such as helminth‐associated changes in adiposity and gut microbiome might also contribute to improved metabolic outcomes. In this review, we summarize epidemiological evidence for the link between helminths and T2D and discuss the potential mechanisms, based on findings from experimental studies as well as the limited number of studies in humans.

Effect of Anthelmintic Treatment on Insulin Resistance: A Cluster-Randomized, Placebo-Controlled Trial in Indonesia

Background Emerging evidence suggests that helminth infections are associated with lower insulin resistance (IR). Current deworming programs might remove this helminth-associated protective effect. Therefore, we evaluated the anthelmintic treatment effect on changes in IR. Methods We conducted a double-blind, household-cluster-randomized, placebo-controlled clinical trial on Flores island, Indonesia, an area endemic for soil-transmitted helminths (STHs). All subjects received 4 rounds of albendazole or matching placebo with 3-month intervals, for 3 consecutive days. The primary outcome was the change in homeostatic model assessment of IR in those aged >16 years. An intention-to-treat analysis was performed involving all subjects and ad hoc in the helminth-infected subjects. Results We examined 797 (in 329 households) and 872 (in 353 households) subjects, who were assigned randomly into the albendazole and placebo arms, respectively. Albendazole was associated with a significant reduction in STH prevalence, total immunoglobulin E (IgE), and eosinophil count. Whereas albendazole had no effect on IR (estimated treatment effect, 0.006 [95% confidence interval, -.010 to .021]; P = .48) at the community level, it was associated with a significant increase in IR (estimated treatment effect, 0.031 [95% confidence interval, .004 to .059]; P = .04) (P value for interaction = .01) among helminth-infected subjects as detected by microscopy. Pathway analysis suggested that this might in part be due to an increased body mass index or a reduced eosinophil count. Conclusions Anthelmintic treatment reduces STH prevalence, total IgE, and eosinophil count but has no effect on IR at the community level. In helminth-infected subjects, treatment significantly increases IR, highlighting the need for metabolic health monitoring with ongoing deworming programs. Clinical Trials Registration ISRCTN 75636394.

Safety and effectiveness of insulin aspart in type 2 diabetic patients: Results from the ASEAN cohort of the A1chieve study

AIM To examine the clinical safety and effectiveness of insulin aspart (IAsp) therapy in type 2 diabetes (T2D) patients from the ASEAN cohort of the international, 24-week, non-interventional A₁chieve study. METHODS T2D patients from Indonesia, Malaysia, Philippines and Singapore, who started IAsp therapy with or without oral glucose-lowering drugs, were included. The primary endpoint was the incidence of serious adverse drug reactions (SADRs), including major hypoglycaemic events. Secondary endpoints included hypoglycaemia, glycated haemoglobin A1c [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPPG], systolic blood pressure [SBP], body weight and lipids. Quality of life (QoL) was assessed using the EQ-5D questionnaire. RESULTS Overall, 312 T2D patients (222 insulin-naive and 90 insulin-experienced) with a mean ± SD age of 56.6 ± 11.2 years, BMI of 24.2 ± 3.9 kg/m(2) and diabetes duration of 7.0 ± 5.7 years were included. The mean daily IAsp dose was 0.51 ± 0.31 U/kg at baseline titrated up to 0.60 ± 0.29 U/kg at Week 24. No SADRs or major hypoglycaemic events were reported in the entire subgroup. The proportion of patients who reported overall hypoglycaemia decreased from baseline to Week 24 (7.1% vs. 0.3%, p < 0.0001). The mean HbA1c improved from 9.5 ± 1.6% at baseline to 7.6 ± 1.3% after 24 weeks (p < 0.001). The mean FPG, post-breakfast PPPG and SBP also improved (p < 0.001). Health-related QoL scores increased in the entire subgroup (mean increase: 9.8 ± 14.6 points, p < 0.001). CONCLUSIONS Starting IAsp therapy was well-tolerated and was associated with significantly improved overall glycaemic control in the ASEAN cohort.