Neil Wintfeld

How accurate are hospital discharge data for evaluating effectiveness of care

Demand for quality of care data has led to publication of adjusted mortality rates of hospitals and physicians. Yet the accuracy of databases used for this purpose is questionable, raising the possibility that consumer-oriented profiles of providers could be misleading. A stratified random sample of discharge abstract records of Medicare-aged patients hospitalized in California were audited by the states health data agency. The results of the audit were analyzed to determine the effect that coding errors have on expected death rates assigned to hospitals as risk-adjustment measures in the annual Medicare hospital mortality report. Discharge abstracts of Medicare-aged patients contained many errors among coded risk factors used to calculate expected death rates. Comorbidities and transfers from nursing homes were seriously underreported and ‘urgency of admission’ was often miscoded. Hospitals differed with respect to error rates (P < 0.001); these varying levels of miscoding caused measurement errors that ranged in size from 0.2 to 2.2 expected 30-day deaths per 100 admissions (10th vs. 90th percentile). Detailed knowledge of the limitations of claims data can help analysts minimize the impact of coding error. Beyond this, quality control of data used for outcomes research needs strengthening.

Indirect comparison of tocilizumab and other biologic agents in patients with rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs.

OBJECTIVES To compare the patterns of American College of Rheumatology (ACR) response between tocilizumab and other biologic agents in patients with rheumatoid arthritis who have inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). METHODS Systematic literature review identified similarly designed double-blind, randomized, placebo-controlled trials over an 18-year period that investigated the effectiveness of abatacept (2), rituximab (2), and TNF-alpha inhibitors etanercept, infliximab, and adalimumab (11) in DMARD-IR patients; data from 3 placebo-controlled, phase 3 trials for tocilizumab, a newly developed IL-6 inhibitor, were included. The endpoint of interest was ACR20/50/70 response criteria at 24 to 30 weeks. Results were analyzed simultaneously using Bayesian mixed-treatment comparison techniques. Nonoverlapping ACR response rates (ACR70) for each agent were compared among treatments to identify differences in ACR response pattern. Separate analyses of overlapping ACR20/50/70 responses were conducted to identify the source of any differences. Results were expressed as relative risk of ACR20/50/70 response and associated 95% credible interval (CrI). RESULTS Patterns across nonoverlapping ACR response levels varied significantly across treatments. In subsequent analyses, the effectiveness of tocilizumab appeared to be comparable to that of other biologic agents for ACR20 and ACR50 responses but greater for ACR70. Specifically, tocilizumab had greater ACR70 responses than both TNF-alpha inhibitors (relative risk = 1.8; CrI = 1.2, 2.6) and abatacept (relative risk = 2.0; CrI = 1.3, 3.1). CONCLUSIONS Among DMARD-IR patients, tocilizumab shows a pattern of response that differs from that of other biologic agents. Post-hoc analyses suggest that the difference lies in a higher likelihood of ACR70 response with tocilizumab.

Peginterferon α-2a (40kD) [Pegasys®] improves HR-QOL outcomes compared with unmodified interferon α-2a [Roferon®-A]: In patients with chronic hepatitis C

AbstractBackground: Use of unmodified interferon α-2a in chronic hepatitis C is associated with impaired health-related quality of life during therapy. Treatment with peginterferon α-2a (40kD) provides an improved sustained response over unmodified interferon α-2a. Objectives: To compare health-related quality of life during treatment for patients receiving peginterferon α-2a (40kD) [Pegasys®] versus unmodified interferon α-2a [Roferon®]. Design: A randomised, international, multicentre, open-label, parallel group study. Setting: 36 centres worldwide. Patients: Interferon-naïve patients (n = 531) with chronic hepatitis C. Interventions: Peginterferon α-2a (40kD) 180µg once a week (n = 267) for 48 weeks or unmodified interferon α-2a 6 million IU three times a week for 12 weeks followed by 36 weeks of 3 million IU three times a week (n = 264). Measurements: Fatigue Severity Scale and 36-item Short-Form Health Survey (SF-36). Results: At weeks 2 and 12, differences favouring peginterferon α-2a (40kD) were seen on seven of eight domains and both summary scores of the SF-36 (p < 0.05 to p < 0.01). At weeks 2, 12 and 24, patients receiving peginterferon α-2a (40kD) had less disabling fatigue (p < 0.01) than those receiving unmodified interferon α-2a. Conclusion: Treatment with peginterferon α-2a (40kD) is associated with less disabling fatigue and less impairment in patient functioning and well-being during treatment than unmodified interferon α-2a. In addition to safety and efficacy, the impact on health-related quality of life may be an important consideration for physicians when selecting an optimal treatment regimen.

Cost Effectiveness of Peginterferon α-2a Plus Ribavirin versus Interferon α-2b Plus Ribavirin as Initial Therapy for Treatment-Naive Chronic Hepatitis C

AbstractIntroduction: In adults with previously untreated chronic hepatitis C (CHC), the combination of peginterferon α-2a plus ribavirin produces a higher rate of sustained virological response (SVR) than interferon α-2b plus ribavirin, but it is still unproven whether this increase is cost effective. The objective of this study was to determine if the gain in SVR with peginterferon α-2a plus ribavirin is worth the incremental cost. Methods: We constructed a Markov model of disease progression in which cohorts of patients received peginterferon α-2a plus ribavirin or interferon α-2b plus ribavirin for 48 weeks (hepatitis C virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genotype non-1 patients without fibrosis), and were followed for their expected lifetimes. The reference patient was a 45-year-old male with CHC without cirrhosis. The SVRs with peginterferon α-2a plus ribavirin and interferon α-2b plus ribavirin used to populate the model were 46% and 36% for patients infected with HCV genotype 1 and 76% and 61% for patients infected with HCV non-1 genotypes, respectively. QOL and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs were in 2002 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was reported from the perspective of the Italian National Health Service. Results: In patients infected with HCV genotype 1, peginterferon α-2a plus ribavirin increased life-years (LYs) by 0.78 years and QALYs by 0.67 years, compared with interferon α-2b and ribavirin. The incremental cost per LY and QALY gained was €9433 and €10 894, respectively. In patients infected with HCV non-1 genotypes, peginterferon α-2a plus ribavirin increased LYs by 1.17 and QALY by 1.01 years, compared with interferon α-2b plus ribavirin. The incremental cost per LY and QALY gained was €3261 and €3766, respectively. Using genotype distribution estimates, the weighted average ICER for all genotypes was €6811 per LY gained and €7865 per QALY gained. Conclusion: Our model suggests that peginterferon α-2a plus ribavirin is cost effective compared with conventional interferon α-2b plus ribavirin for treatment of naive adults with CHC, regardless of HCV genotype, under a wide range of assumptions regarding treatment effectiveness and costs.

Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2a.

Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha‐2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)‐positive (n=271) and HBeAg‐negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 μg peginterferon alpha‐2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health‐related quality of life (HRQL) was assessed using the Short‐Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24‐week treatment‐free follow‐up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88–89 vs 96–100%), serious AEs (4–5 vs 7–16%) and treatment withdrawals (6–8 vs 17–33%). The frequency of depression‐related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. Conclusions: The safety and tolerability of peginterferon alpha‐2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon‐related AEs and a significantly lower incidence of depression.

Treatment of chronic hepatitis C patients with persistently normal alanine aminotransferase levels with the combination of peginterferon α-2a (40 kDa) plus ribavirin: Impact on health-related quality of life

Background:  Peginterferon α‐2a (40 kDa) plus ribavirin is equally effective in chronic hepatitis C patients with normal or elevated alanine aminotransferase (ALT) values. This analysis, in patients with normal ALT levels, compared health‐related quality of life (HRQoL) measurements between untreated control patients and treated patients grouped by virological response. HRQoL in the present population was also compared with HRQoL in patients with elevated ALT levels, observed in a previous study.

Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review

PurposeThis retrospective study compared renal impairment rates in breast cancer, multiple myeloma, prostate cancer and non-small cell lung cancer patients treated with ibandronate or zoledronic acid.Study designMedical records in two German oncology clinics from May 2001 to March 2006 were retrospectively reviewed. Creatinine measurements were analyzed from baseline (before bisphosphonate treatment) to last available measurement for each patient. The Cox proportional hazards model and the Andersen–Gill extension of the Cox model for multiple events analysis were used for multivariate analysis, which controlled for age, clinic site, primary cancer type, baseline SCr or GFR value, prior bisphosphonate use, concomitant use of drugs associated with acute renal failure, and renal-related comorbidities.ResultsOf 333 patients, 109 received ibandronate and 256 received zoledronic acid (32 patients had both drugs). Compared with ibandronate, the zoledronic acid group had a significantly better baseline renal function and fewer patients had a history of renal disease. Zoledronic acid treatment increased the relative risk (RR) and the incidence rate (IR) of renal impairment by ~1.5-fold in all assessed patients (all tumors) compared with ibandronate. Multivariate analysis found significantly higher hazards ratios for zoledronic acid over ibandronate (two to sixfold), after adjusting for differences in characteristics between the two treatment groups.ConclusionsIn this retrospective review, patients were significantly more likely to experience renal impairment with zoledronic acid than with ibandronate.

Health-related quality of life with enfuvirtide (ENF; T-20) in combination with an optimized background regimen.

SummaryThis study assessed the impact of enfuvirtide on health-related quality of life (HRQoL). Patients enrolled in 2 phase 3 trials T-20 versus Optimized Regimen Only (TORO 1 and 2) completed the Medical Outcomes Study (MOS)-HIV questionnaire at baseline and at 4, 8, 16, and 24 weeks. A total of 995 treatment-experienced HIV-1–infected individuals received either self-administered enfuvirtide (90 mg twice daily) + optimized background (OB) or OB alone and had at least 1 follow-up visit. Data from the 2 clinical trials were pooled. Analysis of covariance was used to evaluate changes in the 10 MOS-HIV scale scores and 2 summary scores. Least-squares means for these changes were calculated and used to test for between-group differences. There were no significant between-group differences in any HRQoL measure at baseline. Most MOS-HIV scores showed improvement in the enfuvirtide arm compared with OB alone, although only some of these were significant. Improvements in the general health scale were significantly higher in the enfuvirtide arm compared with OB alone at all post-baseline time points. No scale or summary score for the OB arm showed a significantly greater improvement in score from baseline compared with the enfuvirtide arm, at any time point. The mental health summary score at 24 weeks was significantly higher in the enfuvirtide arm compared with OB alone. Enfuvirtide in addition to an OB regimen does not adversely affect and may improve HRQoL when self-administered for up to 24 weeks by treatment-experienced, HIV-1–infected individuals.

Renal toxicity in patients with multiple myeloma receiving zoledronic acid vs. ibandronate: A retrospective medical records review

AIMS This retrospective study investigated the rates of renal impairment in patients with multiple myeloma treated with zoledronic acid and ibandronate. MATERIALS AND METHODS We retrospectively reviewed medical records in a German oncology clinic, from May 2001 to December 2005. Creatinine measurements were analyzed from baseline (before zoledronic acid or ibandronate treatment) to last evaluation for each patient. A total of 84 patients were included. RESULTS Zoledronic acid increased the risk of renal impairment by approximately 3-fold compared with ibandronate (renal impairment rates: zoledronic acid 37.7% vs. ibandronate 10.5%, relative risk [RR]=3.6, P=0.0029 serum creatinine [SCr]; 62.3% vs. 23.7%, RR=2.6, P=0.0001 glomerular filtration rate [GFR]). Ibandronate-treated patients switched from zoledronic acid had a significantly higher risk of renal impairment than patients receiving ibandronate monotherapy (zoledronic acid over ibandronate 39.1% vs. ibandronate monotherapy 6.7%, RR= 5.9, P=0.028 [SCr]; 65.2% vs 26.7%, RR=2.4, P=0.022 [GFR]). Multivariate analysis found significantly higher hazard ratios for zoledronic acid over ibandronate (SCr: Cox = 4.38, P=0.01; Andersen-Gill=8.22, P < 0.01; GFR: Cox = 4.31, P < 0.01; Andersen-Gill = 3.71, P < 0.01). CONCLUSIONS Overall, this retrospective study suggests that multiple myeloma patients are more likely to experience renal impairment with zoledronic acid than with ibandronate. The risk of renal impairment increased if patients had received prior therapy with zoledronic acid.

Cost-Effectiveness of Enfuvirtide for Treatment- Experienced Patients with HIV in Italy

Abstract Background: Enfuvirtide (ENF) plus an optimized background (OB) antiretroviral regimen delays virological failure (VF), reduces HIV-1 viral load, and increases CD4 count compared with OB only in pretreated patients. Purpose: To forecast long-term outcomes, costs, and cost-effectiveness of ENF+OB vs. OB in the Italian health care system. Method: A Markov model was developed and clinical trial results on viral suppression and CD4 count were linked with data from HAART-era studies of the risk of AIDS-defining events (ADEs) and death. Resource data were obtained from Italian sources on direct medical costs. Cost-effectiveness was computed as the incremental cost per quality-adjusted life year (QALY) saved. Results: Patients receiving ENF+OB were projected to experience a mean time to virological failure of 1.0 years vs. 0.5 years for OB and mean time to immunological failure of 3.1 years vs. 1.3 years for OB. Life expectancy and QALYs were greater for ENF+OB than OB by 1.8 and 1.5 years, respectively. Total lifetime medical cost was €126,487 for ENF+OB and €84,416 for OB, a difference of €42,071 due to the cost of ENF itself (€18,400) and the medical costs associated with additional life expectancy (€23,671). The incremental cost-effectiveness of ENF+OB was €23,721 per life year (€28,669 per QALY). Conclusion: ENF+OB is predicted to increase life expectancy at a cost per life year that is comparable to many well-accepted therapies in Europe.