Evaluation of quality of life in a clinical trial with nonrandom dropout: the effect of epoetin alfa in anemic cancer patients.

Quality of life (QOL) endpoints from a randomized, placebo-controlled trial of anemic cancer patients treated with nonplatinum-containing chemotherapy who received epoetin alfa or placebo were subjected to a sensitivity analysis. Three QOL instruments were used: the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Cancer Linear Analog Scale (CLAS), and the Medical Outcomes Study Short Form-36 (SF-36). The seven primary endpoints chosen a priori for analysis were: the Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-An fatigue subscale, CLAS energy, CLAS daily activities, CLAS overall QOL, and the SF-36 physical and mental component summary scales. Lower QOL scores were reported for patients who discontinued early, suggesting a nonrandom dropout process. Significant correlations (ranging from 0.37 to 0.77) between individual rates of change and the time to early termination of therapy or death supported this conclusion. Estimates of within-treatment-arm QOL change over time are more conservative with the missing not at random (MNAR) assumption as compared with the more optimistic estimates with the assumption that missing QOL data are missing at random (MAR). However, the between-treatment-arm comparisons were consistent across analyses, demonstrating statistically significant differences in favor of the epoetin alfa arm for four of the seven outcome measures.

Assessing the clinical significance of health-related quality of life (HrQOL) improvements in anaemic cancer patients receiving epoetin alfa.

Health-related quality of life (HrQOL) assessments are gaining importance as outcome measures in cancer clinical trials. A recently published clinical trial reported statistically significant (P<0.001) increases in haemoglobin (Hb) levels and significantly (P<0.01) increased HrQOL scores following the administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) versus placebo to anaemic cancer patients who received non-platinum chemotherapy. This study employed five cancer-specific HrQOL instruments. Hb and HrQOL data from this trial were analysed to estimate the minimally important difference (MID) in HrQOL measures that could be interpreted as clinically meaningful, with Hb level selected as the best external standard. Patients were assigned to two groups: improved (Hb increases of >/=1 g/dL) or stable (change in Hb of-1 g/dL to <1 g/dL). The MID was first determined as the difference between the mean changes in HrQOL in the improved group versus the stable group. By this analysis, the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinically important for all Hb-sensitive, cancer-specific HrQOL evaluations. Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinically significant. These analyses were repeated using a data set from a separate clinical trial, which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre, double-blind study were clinically important. These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials.

A cost analysis of diabetic lower-extremity ulcers.

OBJECTIVE: Our objectives were to 1) estimate the prevalence of diabetes and diabetic lower-extremity ulcers in the Medicare population, 2) characterize Medicare population-specific costs for lower-extremity ulcer episodes, and 3) evaluate potential cost savings associated with better healing of lower-extremity ulcers. RESEARCH DESIGN AND METHODS: Prevalence and costs of diabetic lower-extremity ulcers were obtained by an analysis of Medicare claims data from 1995 and 1996 Standard Analytic Files (5% sample). RESULTS: Medicare expenditures for lower-extremity ulcer patients were on average 3 times higher than those for Medicare patients in general ($15,309 vs. $5,226). Lower-extremity ulcer-related spending accounted for 24% of total spending for lower-extremity ulcer patients. Most of the ulcer-related costs accrued on the inpatient side (73.7%); proportionately smaller amounts went to physicians and nursing home facilities. To determine the potential effect of better diabetic ulcer management, a model was created that estimated the impact on costs with improved healing rates. Improving the 20-week healing rate from 31 to 40% would save Medicare $189 per episode. CONCLUSIONS: Lower-extremity ulcers cost the Medicare system $1.5 billion in 1995. Any wound care intervention that could prevent even a small percentage of wounds from progressing to the stage at which inpatient care is required may have a favorable cost effect on the Medicare system.

Pharmacoeconomics of chronic nonmalignant pain.

Pain is one of the most common reasons for patients to seek medical care. In most settings, the model of acute pain treatment, with its emphasis on pharmacological therapy, is used for acute and chronic pain alike. Persistent chronic pain, however, often leads to complex social and psychological maladaptations, as well as substantial direct and indirect costs. Thus, the proper treatment of chronic pain usually involves pharmacological, behavioural and psychological interventions. Pain is a subjective sensation, but persistent chronic pain often results in long term neurophysiological and psychological changes that might be more appropriately considered disease manifestations. Unfortunately, the subjectivity of pain has meant that the assessment of the epidemiology, pharmacotherapy and economic costs of chronic pain has been difficult. As a result, many of the techniques for chronic pain management are unfamiliar to practising physicians. Even those healthcare professionals who are familiar with the special techniques for the management of chronic pain may be unable to identify the subpopulations for which they might be most effective. The clinician must evaluate patients for the appropriateness of a number of alternative drug delivery methods, novel analgesic agents, neuromodulatory techniques and multidisciplinary behavioural and psychological treatment programmes. The most effective treatment will often involve a combination of these techniques, as determined by the unique features of the patient's pain condition as well as individual patient characteristics. The costs and outcomes of various treatment strategies vary considerably and there is a need for comparative studies. Increasing emphasis on diagnosis and treatment in the primary care setting will place more importance on knowing the relative efficacies and appropriate use of a widening array of choices for chronic pain treatment. The management of chronic pain is remarkably complex and resource-intensive, and there is clearly a need for more intensive pharmacoeconomic studies, especially those comparing the many alternative strategies for management.