Adjustment of publication bias using a cumulative meta-analytic framework.

OBJECTIVES: Publication bias has the potential to adversely impact clinical decision making and patient health if alternative decisions would have been made had there been complete publication of evidence. METHODS: The objective of our analysis was to determine if earlier publication of the complete evidence on rosiglitazone's risk of myocardial infarction (MI) would have changed clinical decision making at an earlier point in time. We tested several methods for adjustment of publication bias to assess the impact of potential time delays to identifying the MI effect. We then performed a cumulative meta-analysis (CMA) for both published studies (published-only data set) and all studies performed (comprehensive data set). We then created an adjusted data set using existing methods of adjustment for publication bias (Harbord regression, Peter's regression, and the nonparametric trim and fill method) applied to the limited data set. Finally, we compared the time to the decision threshold for each data set using CMA. RESULTS: Although published-only and comprehensive data sets did not provide notably different final summary estimates [OR = 1.4 (95 percent confidence interval [CI]: .95-2.05) and 1.42 (95 percent CI: 1.03-1.97)], the comprehensive data set reached the decision threshold 36 months earlier than the published-only data set. All three adjustment methods tested did not show a differential time to decision threshold versus the published-only data set. CONCLUSIONS: Complete access to studies capturing MI risk for rosiglitazone would have led to the evidence reaching a clinically meaningful decision threshold 3 years earlier.

An assessment of data quality in a multi-site electronic medical record system in Haiti.

OBJECTIVES: Strong data quality (DQ) is a precursor to strong data use. In resource limited settings, routine DQ assessment (DQA) within electronic medical record (EMR) systems can be resource-intensive using manual methods such as audit and chart review; automated queries offer an efficient alternative. This DQA focused on Haiti's national EMR - iSanté - and included longitudinal data for over 100,000 persons living with HIV (PLHIV) enrolled in HIV care and treatment services at 95 health care facilities (HCF). METHODS: This mixed-methods evaluation used a qualitative Delphi process to identify DQ priorities among local stakeholders, followed by a quantitative DQA on these priority areas. The quantitative DQA examined 13 indicators of completeness, accuracy, and timeliness of retrospective data collected from 2005 to 2013. We described levels of DQ for each indicator over time, and examined the consistency of within-HCF performance and associations between DQ and HCF and EMR system characteristics. RESULTS: Over all iSanté data, age was incomplete in <1% of cases, while height, pregnancy status, TB status, and ART eligibility were more incomplete (approximately 20-40%). Suspicious data flags were present for <3% of cases of male sex, ART dispenses, CD4 values, and visit dates, but for 26% of cases of age. Discontinuation forms were available for about half of all patients without visits for 180 or more days, and >60% of encounter forms were entered late. For most indicators, DQ tended to improve over time. DQ was highly variable across HCF, and within HCFs DQ was variable across indicators. In adjusted analyses, HCF and system factors with generally favorable and statistically significant associations with DQ were University hospital category, private sector governance, presence of local iSante server, greater HCF experience with the EMR, greater maturity of the EMR itself, and having more system users but fewer new users. In qualitative feedback, local stakeholders emphasized lack of stable power supply as a key challenge to data quality and use of the iSanté EMR. CONCLUSIONS: Variable performance on key DQ indicators across HCF suggests that excellent DQ is achievable in Haiti, but further effort is needed to systematize and routinize DQ approaches within HCFs. A dynamic, interactive "DQ dashboard" within iSanté could bring transparency and motivate improvement. While the results of the study are specific to Haiti's iSanté data system, the study's methods and thematic lessons learned holdgeneralized relevance for other large-scale EMR systems in resource-limited countries.

Inclusion of patient-reported outcome measures in registered clinical trials: Evidence from ClinicalTrials.gov (2007-2013).

BACKGROUND: Patient reported outcomes (PROs) have gained a prominent place in clinical research. Previous estimates suggest that PRO measures are used in 14% of clinical trials. Online registries, such as ClinicalTrials.gov, may be useful in evaluating extent of PRO use. PURPOSE: To estimate the proportion of clinical trials using at least one PRO measure and to examine associations between trial characteristics and use of PRO measures. METHODS: A copy of the ClinicalTrials.gov database was made, containing all data from November 2007 to December 2013. Content was searched for use of PRO measures. Multivariable logistic regression was used to investigate possible associations between trial-level characteristics and use of PRO measures. RESULTS: Of 96,736 registered trials, 26,337 (27%) were identified as using one or more PRO measures. Among oncology trials, 29% (3947/13,584) were identified as using a PRO measure, compared to 27% (22,390/83,152) of non-oncology trials. A greater proportion of trials using PRO measures were more likely to be sponsored by university/research organizations (29%) or the US government (33%), compared to industry (22%); Phase III (35%); non-randomized (32%); and evaluating devices (30%), procedures (31%) or behaviors (50%), compared to drugs (24%). Fewer were FDA-regulated (23%). CONCLUSIONS: Evidence suggests that between 2007 and 2013, there has been an increase in the number of trials that use a PRO measure, particularly in oncology trials. With initiatives such as the Patient-Focused Drug Development and FDA PRO Guidance, the trend in the use of PRO measures in clinical research will likely increase further.

The association between use of a clinical decision support tool and adherence to monitoring for medication-laboratory guidelines in the ambulatory setting.

BACKGROUND: Stage 2 Meaningful Use criteria require the use of clinical decision support systems (CDSS) on high priority health conditions to improve clinical quality measures. Although CDSS hold great promise, implementation has been fraught with challenges, evidence of their impact is mixed, and the optimal method of content delivery is unknown. OBJECTIVE: The authors investigated whether implementation of a simple clinical decision support (CDS) tool was associated with improved prescriber adherence to national medication-laboratory monitoring guidelines for safety (hepatic function, renal function, myalgias/rhabdomyolysis) and intermediate outcomes for antidiabetic (Hemoglobin A(1c); HbA(1c)) and antihyperlipidemic (low density lipoprotein; LDL) medications prescribed within a diabetes registry. METHODS: This was a retrospective observational study conducted in three phases of CDS implementation (2008-2009): pre-, transition-, and post-Prescriptions evaluated were ordered from an electronic health record within a multispecialty medical group. Adherence was evaluated within and without applying guideline-imposed time constraints. RESULTS: Forty-thousand prescriptions were ordered over three timeframes. For hepatic and renal function, the proportion of prescriptions for which labs were monitored at any time increased from 52% to 65% (p<0.001); those that met time guidelines, from 14% to 21% (p<0.001). Only 6% of required labs were drawn to monitor for myalgias/rhabdomyolysis, regardless of timeframe. Over 90% of safety labs were within normal limits. The proportion of labs monitored at any time for LDL increased from 56% to 64% (p<0.001); those that met time guidelines from 11% to 17% (p<0.001). The proportion of labs monitored at any time for HbA(1c) remained the same (72%); those that met time guidelines decreased from 45% to 41% (p<0.001). CONCLUSION: A simple CDS tool may be associated with improved adherence to guidelines. Efforts are needed to confirm findings and improve the timeliness of monitoring; investigations to optimize alerts should be ongoing.

The impact of an ambulatory CPOE system on medication errors.

Few studies have evaluated the impact of an ambulatory computerized physician order entry (CPOE) system on medication errors. We conducted a retrospective analysis of 10,172 prescriptions to evaluate the impact of a basic CPOE system on prescribing-related medication errors, and found a significant decrease in the occurrence of errors.

The cost of treating ribavirin-induced anemia in hepatitis C: the impact of using recombinant human erythropoietin.

OBJECTIVE: Ribavirin-induced anemia (RIA) is a common adverse effect of chronic hepatitis C treatment. Studies have shown that the use of epoetin decreases the need for ribavirin dose reduction or discontinuation. The primary objective was to calculate the incremental cost of treating hepatitis C in those without versus with RIA, using either the strategy of ribavirin dose reduction/discontinuation or epoetin. The secondary objective was to calculate the incremental cost of using epoetin versus no epoetin to treat RIA, per ribavirin dose reduction/discontinuation averted. METHODS: Estimates from the literature and decision-analytic techniques were used to model treatment patterns and estimate the cost of managing RIA in genotype 1, 2, and 3 subjects. Sensitivity analyses were used to address uncertainty. RESULTS: Clinically significant RIA, a reduction in hemoglobin of > or = 2 g/dL (1.2 mmol/L), developed in 72% of patients in observational studies. The incremental cost of treating chronic hepatitis C decreased when employing the strategy of ribavirindose reduction/discontinuation to treat RIA, and increased by 5.7% (genotype 1) or 34.4% (genotype 2 or 3), when using epoetin. Using one-way sensitivity analyses, the cost of using epoetin per ribavirin dose reduction/discontinuation averted was $39,579-$52,023. Generalizability may be limited to settings in which a similar proportion of patients develop RIA. CONCLUSIONS: The proportional cost of treating hepatitis C when using epoetin to treat RIA is significant in genotype 2 or 3 patients. The cost of using epoetin per ribavirin dose reduction/discontinuation averted is substantial in patients with genotypes 1, 2, or 3; and varies with the probability of response to epoetin. These findings suggest that additional studies are warranted that will determine the effect of epoetin on treatment outcomes and its role as supportive therapy in patients with RIA.

Management strategies for ribavirin-induced hemolytic anemia in the treatment of hepatitis C: clinical and economic implications.

OBJECTIVES: Recently published studies have demonstrated increased efficacy and cost-effectiveness of combination therapy with interferon and alpha-2b/ribavirin compared with interferon-alpha monotherapy in the treatment of chronic hepatitis C (CHC). Combination therapy is associated with a clinically important adverse effect: ribavirin-induced hemolytic anemia (RIHA). The objective of this study was to evaluate the direct health-care costs and management of RIHA during treatment of CHC in a clinical trial setting. METHODS: A systematic literature review was conducted to synthesize information on the incidence and management of RIHA. Decision-analytic techniques were used to estimate the cost of treating RIHA. Uncertainty was evaluated using sensitivity analyses. RESULTS: RIHA, defined as a reduction in hemoglobin to less than 100 g/L, occurs in approximately 7% to 9% of patients treated with combination therapy. The standard of care for management of RIHA is reduction or discontinuation of the ribavirin dosage. We estimated the direct cost of treating clinically significant RIHA to be $170 per patient receiving combination therapy per 48-week treatment course (range $68-$692). The results of the one-way sensitivity analyses ranged from $57 to $317. In comparison, the cost of 48 weeks of combination therapy is $16,459. CONCLUSIONS: The direct cost of treating clinically significant RIHA is 1% ($170/$16,459) of drug treatment costs. Questions remain about the optimal dose of ribavirin and the incidence of RIHA in a real-world population. Despite these uncertainties, this initial evaluation of the direct cost of treating RIHA provides an estimate of the cost and management implications of this clinically important adverse effect.

Direct medical costs of chronic obstructive pulmonary disease: chronic bronchitis and emphysema.

In this study we aimed to estimate direct medical costs of Chronic Obstructive Pulmonary Disease (COPD) by disease type; chronic bronchitis and emphysema. This study estimates direct costs in 1996 dollars using a prevalence approach and both aggregate and microcosting. A societal perspective is taken using prevalence, and multiple national, state and local data sources are used to estimate health-care utilization and costs. Chronic bronchitis and emphysema together account for $14.5 billion in annual direct costs. Inpatient costs are greater than outpatient and emergency costs ($8.3 vs. $7.8 billion) and hospital and medication costs account for most resources spent. The high prevalence of chronic bronchitis accounts for its larger total costs ($11.7 billion) compared with emphysema ($2.8 billion). Emphysema, which is more severe, has higher costs per prevalent case ($1341 vs. $816). Hospital stays account for the highest costs, $6.0 billion for chronic bronchitis and $1.9 billion for emphysema. The hospitalization rate, length of stay and average cost per prevalent case are higher for emphysema than for chronic bronchitis. Medication costs are the second highest cost category ($4.4 billion for chronic bronchitis, $0.693 billion for emphysema). The high hospitalization and low home care costs (0.2% of total) suggest underuse of home care and room to shift from acute to preventive care. More attention to healthcare management of chronic bronchitis and emphysema is suggested, and improving inhaler and anti-smoking compliance might be important targets.