Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy.

BACKGROUND: In a recent randomised, double-blind, phase III clinical trial among 1195 patients with metastatic castration-resistant prostate cancer (mCRPC) who had failed docetaxel chemotherapy, abiraterone acetate was shown to significantly prolong overall survival compared with prednisone alone. Here we report on the impact of abiraterone therapy on the health-related quality of life (HRQoL) observed during this trial, assessed using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. METHODS: All analyses were conducted using prespecified criteria for clinically meaningful improvement and deterioration in FACT-P total score as well as subscale scores; all respective thresholds were defined using an accepted methodology. Improvement was assessed only in patients with clinically significant functional status impairment at baseline. RESULTS: Significant improvements in the FACT-P total score were observed in 48% of patients receiving abiraterone versus 32% of patients receiving prednisone (p < 0.0001). Also, the median time to deterioration in FACT-P total score was longer (p < 0.0001) in patients receiving abiraterone (59.9 weeks versus 36.1 weeks). Similar differences were observed in all FACT-P subscales, with the exception of the social/family well-being domain. Median time to improvement in the physical well-being domain and the trial outcome index was significantly shorter (p < 0.01) with abiraterone when compared with the prednisone arm. CONCLUSIONS: The previously demonstrated survival benefit for abiraterone is accompanied by improvements in patient-reported HRQoL and a significant delay in HRQoL deterioration when compared with prednisone.

Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial.

BACKGROUND: Bone metastases are a major cause of morbidity in metastatic castration-resistant prostate cancer. Abiraterone acetate potently disrupts intracrine androgen receptor signalling pathways implicated in the progression of the disease, including bone metastases. We assessed data for pain control and skeletal-related events prospectively collected as part of the randomised, phase 3 COU-AA-301 trial of abiraterone acetate plus prednisone versus placebo plus prednisone in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy. METHODS: The COU-AA-301 trial enrolled patients with metastatic castration-resistant prostate cancer in whom one or two lines of chemotherapy (one docetaxel based) had been unsuccessful and who had Eastern Cooperative Oncology Group performance statuses of 2 or less. Pain intensity and interference of pain with daily activities were assessed with the Brief Pain Inventory-Short Form questionnaire at baseline, day 15 of cycle 1, and day 1 of each treatment cycle thereafter until discontinuation. We assessed, with prospectively defined response criteria that incorporated analgesic use, clinically meaningful changes in pain intensity and interference with daily living. We measured time to first occurrence of skeletal-related events, which we defined as pathological fracture, spinal cord compression, palliative radiation to bone, or bone surgery, and regularly assessed them throughout the study. Pain palliation was assessed in patients who had clinically significant baseline pain, whereas all other analyses were done in the overall intention-to-treat population. COU-AA-301 is registered with ClinicalTrials.gov, number NCT00638690. FINDINGS: Median follow-up was 20·2 months (IQR 18·4-22·1). In patients with clinically significant pain at baseline, abiraterone acetate and prednisone resulted in significantly more palliation (157 of 349 [45·0%] patients vs 47 of 163 [28·8%]; p=0·0005) and faster palliation (median time to palliation 5·6 months [95% CI 3·7-9·2] vs 13·7 months [5·4-not estimable]; p=0·0018) of pain intensity than did prednisone only. Palliation of pain interference (134 of 223 [60·1%] vs 38 of 100 [38·0%], p=0·0002; median time to palliation of pain interference 1·0 months [95% CI 0·9-1·9] vs 3·7 months [2·7-not estimable], p=0·0004) and median duration of palliation of pain intensity (4·2 months [95% CI 3·0-4·9] vs 2·1 months [1·4-3·7]; p=0·0056) were significantly better with abiraterone acetate and prednisone than with prednisone only. In the overall population, median time to occurrence of first skeletal-related event was significantly longer with abiraterone acetate and prednisone than with prednisone only (25·0 months [95% CI 25·0-not estimable] vs 20·3 months [16·9-not estimable]; p=0·0001). INTERPRETATION: In patients with metastatic castration-resistant prostate cancer previously treated with docetaxel, abiraterone acetate and prednisone offer significant benefits compared with prednisone alone in terms of pain relief, delayed pain progression, and prevention of skeletal-related events. FUNDING: Janssen Research & Development and Janssen Global Services.

Personal and social functioning in schizophrenia: defining a clinically meaningful measure of maintenance in relapse prevention.

BACKGROUND: Relapse prevention and maintenance of social functioning are important treatment objectives in the long-term management of schizophrenia. However, relatively little is known about measuring maintenance of social functioning to assess treatment benefit in relapse prevention clinical trials or as a tool to predict relapse in clinical practice. This study aims (1) to define a clinically meaningful decrease in the Personal and Social Performance scale (PSP) to assess antipsychotic treatment benefit in terms of maintenance of functioning and (2) to explore the threshold value of PSP decline as a useful tool to predict relapse in clinical practice. METHODS: This post hoc analysis of two similar placebo-controlled relapse prevention clinical trials consisted of an exploration of change in PSP that would represent a clinically important decrement to measure treatment benefit in terms of time to PSP decrement (ITT analysis set; Study 1: n = 205) and an assessment of predictive value of PSP decrement and relapse status (ITT analysis set; Study 2: n = 408). RESULTS: A 10-point decrement in PSP score was the threshold value for a clinically meaningful decline in personal and social functioning in a relapse prevention trial (Study 1). A strong association was found with relapse status: 61% of subjects with at least a 10-point decrease in PSP experienced the decrement prior to (between start of double-blind phase and before day of relapse) or on the day of relapse (Study 2). Kaplan-Meier survival analysis of time to at least a 10-point decrement in PSP showed that the proportion of subjects who did not experience at least a 10-point PSP decrease was statistically significantly greater in the paliperidone palmitate group than in the placebo group (p = 0.0014) (Study 2). CONCLUSIONS: Findings suggest a 10-point PSP decrement is a clinically relevant measure of maintenance of functioning in patients stabilized with antipsychotic therapy. Paliperidone palmitate demonstrated a statistically significant treatment benefit in terms of maintenance of functioning versus placebo. Furthermore, measuring a clinically relevant PSP decrement may be useful as an early functional indicator of relapse in clinical practice. LIMITATIONS: The exploration and validation of the threshold value of change in the PSP was designed and conducted post hoc. Predictive value is limited by the frequency in which PSP assessments were carried out in these trials, underscoring the importance of regular assessment.

Measuring social functioning with the personal and social performance scale in patients with acute symptoms of schizophrenia: interpretation of results of a pooled analysis of three Phase III trials of paliperidone extended-release tablets.

BACKGROUND: The safety and efficacy of paliperidone extended-release tablets (paliperidone ER) in patients with acute symptoms of schizophrenia have been described in 3 randomized, double-blind, 6-week, placebo-controlled, fixed-dose, Phase III clinical trials. The validity and reliability of the Personal and Social Performance (PSP) scale, both in patients with acute symptoms of schizophrenia and those with stabilized symptoms, have also been reported. OBJECTIVE: The aim of this work was to estimate the treatment benefit of paliperidone ER compared with placebo in terms of improvements in personal and social functioning as measured by the PSP scale in 3 controlled clinical trials. METHODS: Data were derived from 3 paliperidone ER multicenter Phase III pivotal studies of patients with acute symptoms of schizophrenia. Each study included a randomized, double-blind, placebo- and active-controlled, parallel-group, 6-week treatment period with an open-label extension of paliperidone ER treatment. Patients were randomized to receive paliperidone ER, olanzapine 10 mg, or placebo once daily. Paliperidone ER doses were 3, 9, and 15 mg/d in 1 study; 6, 9, and 12 mg/d in another; and 6 and 12 mg/d in the third. Collectively, 1306 intent-to-treat patients received placebo or paliperidone ER in these 3 trials. Most (61.7%) were white; 21.6% were black, 8.8% were Asian, and 7.9% were of another race. The mean age ranged from 36.3 to 39.4 years across treatment groups. Multiple analyses were applied to PSP data (for which higher scores indicate better personal and social functioning) from these paliperidone ER studies: between-group minimum important difference (MID) estimates; responder analyses; between-group cumulative frequency comparisons of PSP change from baseline to end point; and number-needed-to-treat (NNT) estimates. RESULTS: Standardized differences and effect sizes between paliperidone ER and placebo in PSP mean change from baseline to end point ranged from 0.52 to 0.85 for all paliperidone ER doses. Observed between-group differences (paliperidone ER minus placebo) in PSP mean change from baseline to end point exceeded the between-group MID of 7 points at all paliperidone ER doses. The percentage of patients achieving at least one 10-point category improvement in the PSP was higher with all paliperidone ER doses (range, 49.6%-63.6%) than placebo (33.1%) (P < 0.005). Across the distribution of all possible PSP scores, the percentage of patients achieving any level of change appeared to be greater for paliperidone ER than for placebo at all doses. Derived NNTs for improved personal and social functioning based on paliperidone ER trials ranged from 3.3 to 6.1. The improvement in personal and social functioning achieved by patients receiving paliperidone ER during the double-blind studies was maintained throughout the 52-week, open-label extension studies, as assessed using multiple definitions of response; subjects in the placebo arm during doubleblind treatment appeared to achieve and maintain improved functioning when switched to paliperidone ER for the extension studies. CONCLUSION: These results suggest that paliperidone ER had a meaningful treatment benefit with respect to improving personal and social functioning in these patients with acute symptoms of schizophrenia.

Reliability, validity and ability to detect change of the clinician-rated Personal and Social Performance scale in patients with acute symptoms of schizophrenia.

OBJECTIVE: To describe the measurement properties of the Personal and Social Performance scale (PSP), a clinician-reported measure of severity of personal and social dysfunction, in subjects with acute symptoms of schizophrenia. METHODS: Pooled data from three paliperidone extended-release clinical studies (n = 1665) and data from a separate noninterventional, cross-sectional, validation study (n = 299) were analyzed. RESULTS: The PSP showed good interrater (intraclass correlation coefficient [ICC] = 0.87) and test-retest (ICCs > 0.90) reliability. Pearson correlation coefficient for association between baseline PSP and Positive and Negative Syndrome Scale (PANSS) total scores was -0.32 for subjects assessed by the same rater and -0.29 for subjects assessed by different raters, suggesting low overlap in measurement constructs between the PANSS and PSP. Spearman Rank correlation coefficient for association between baseline PSP and Clinical Global Impression-Severity (CGI-S) scores was -0.51 with the same rater and -0.15 with different raters. Hypothesized relationships between the PSP and the PANSS or CGI-S based on levels of disease severity were prospectively defined. These hypotheses were confirmed by analyses showing statistically significant differences between baseline mean PSP scores in subjects grouped by severity rating on the CGI-S (mild or less vs. at least moderate) (p < 0.001) and the PANSS ('low symptom severity' vs. 'high symptom severity') (p = 0.005). The PSP was sensitive to change based on statistically significant correlations between change in the PSP and change in the CGI-S (p < 0.001) and the PANSS (p < 0.001). Limitations of analyses include pooling data across studies, interrater reliability assessment in the validation study only, post hoc assessment of test-retest reliability in the paliperidone ER studies, different raters for the PSP and PANSS not specified in the paliperidone ER studies, PSP validity assessment based on the PANSS and the CGI-S as comparators rather than another social function instrument. CONCLUSION: These initial reliability and validity assessments suggest the PSP has promise as a measure of social functioning in patients with acute symptoms of schizophrenia.

The Premature Ejaculation Profile: validation of self-reported outcome measures for research and practice.

OBJECTIVE: To evaluate the reliability and validity of the Premature Ejaculation Profile (PEP), a self-reported outcome instrument for evaluating domains of PE and its treatment, comprised of four single-item measures, a profile, and an index score. SUBJECTS AND METHODS: Data were from men participating in observational studies in the USA (PE, 207 men; non-PE, 1380) and Europe (PE, 201; non-PE, 914) and from men with PE (1238) participating in a phase III randomized, placebo-controlled clinical trial of dapoxetine. The PEP contains four measures: perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse, and interpersonal difficulty related to ejaculation, each assessed on five-point response scales. Test-retest reliability, known-groups validity, and ability to detect a patient-reported global impression of change (PGI) in condition were evaluated for the individual PEP measures and a PEP index score (the mean of all four measures). Profile analysis was conducted using multivariate analysis of variance. RESULTS: All PEP measures showed acceptable reliability (intraclass correlation coefficients ranged from 0.66 to 0.83) and mean scores for all measures differed significantly between PE and non-PE groups (P < 0.001). Men who reported a reduction in PE with treatment in the phase III trial had significantly greater scores on each of the four measures. The PEP profiles of men with and without PE differed significantly (P < 0.001) in both observational studies; higher levels of PGI were associated with higher PEP profiles (P < 0.001). The PEP index score also showed acceptable reliability and was significantly different between the PE and non-PE groups (P < 0.001). Men who reported an improvement in PE with treatment in the phase III trial had significantly greater PEP index scores. In the phase III trial, nausea was the most common adverse event with dapoxetine. CONCLUSION: The PEP provides a reliable, valid, and interpretable measure for use in monitoring outcomes of men with PE.

Reliability, validity and ability to detect change of the Personal and Social Performance scale in patients with stable schizophrenia.

This report describes the measurement properties of the Personal and Social Performance scale (PSP), a clinician-reported measure of severity of personal and social dysfunction, in an outpatient population with stabilized schizophrenia. Pooled data from two similar antipsychotic clinical studies were analyzed (n=411). The PSP showed good test-retest reliability (intraclass correlation coefficient=0.79). The PSP was more highly correlated with the Strauss-Carpenter Level of Function, an instrument measuring a similar construct, than the Positive and Negative Syndrome Scale, an instrument measuring a different construct. There was a statistically significant difference between mean PSP scores in subjects grouped by their severity rating on the Clinical Global Impression-Severity (CGI-S) (mild or less versus at least moderate), indicating the ability to discriminate between known groups. Effect sizes for mean change in the PSP based on 1-category improvement (0.72) or worsening (-0.88) versus no change in the CGI-S were moderate to large, demonstrating the ability to detect change. Estimates of between-group minimum important difference suggest that a 7-point improvement in the PSP may be clinically meaningful in a clinical trial setting. Initial reliability and validity assessments suggest the PSP may be a useful measure of social functioning in patients with stable schizophrenia.

Premature ejaculation: results from a five-country European observational study.

OBJECTIVES: To characterize premature ejaculation (PE) in five European countries using intravaginal ejaculatory latency time (IELT) and the Premature Ejaculation Profile (PEP). METHODS: This 8-wk, multicenter, observational study enrolled men >or=18 yr of age and their female partners. Clinicians diagnosed PE using the DSM-IV-TR criteria and at least moderate, subject-reported, ejaculation-related personal distress or interpersonal difficulty. The PEP was administered at baseline and weeks 4 and 8. Partners measured IELT; the average stopwatch-measured IELT for each 4-wk period was calculated and compared with the man's screening-estimated IELT. Relationships between individual PEP measures and IELT were assessed with path analysis. RESULTS: PE was diagnosed in 201 of 1115 men. Findings were similar to those in a similarly conducted US study. Mean IELT was lower in the PE versus the non-PE group (3.3 vs. 10.0min, respectively), but substantial overlap was observed. Men with PE and their partners reported significantly worse control over ejaculation, ejaculation-related personal distress, satisfaction with sexual intercourse, and ejaculation-related interpersonal difficulty than men without PE and their partners. Path analysis showed that perceived control over ejaculation had a significant effect on ejaculation-related personal distress and satisfaction with sexual intercourse; IELT had an effect on control over ejaculation, no direct effect on satisfaction with sexual intercourse, and a small direct effect on ejaculation-related personal distress. CONCLUSIONS: No major cultural differences existed between EU and US men with and without PE and their female partners. These results emphasize the importance of the PEP measures, especially perceived control over ejaculation, in characterizing PE.

Correlates to the clinical diagnosis of premature ejaculation: results from a large observational study of men and their partners.

PURPOSE: A recent observational study characterized intravaginal ejaculatory latency time and single item patient reported outcome measures in a large population of males with and without premature ejaculation, as well as their female partners. In the current analysis we assessed the relative influence of those measures in identifying premature ejaculation as diagnosed by the clinician. MATERIALS AND METHODS: Data were from a 4-week, multicenter, observational study of men with (207) and without (1,380) premature ejaculation (diagnosed using The Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria), as well as their female partners. Estimated and measured intravaginal ejaculatory latency time, age, and responses to single item (control over ejaculation, personal distress, satisfaction with sexual intercourse and interpersonal difficulty) and multiple item (male and female Golombok-Rust Inventory of Sexual Satisfaction, male Self-Esteem and Relationship questionnaire, and Short Form 36) measures were evaluated with stepwise logistic regression analysis. RESULTS: Self-estimated and stopwatch measured intravaginal ejaculatory latency time were interchangeable, correctly assigning premature ejaculation status with 80% sensitivity and 80% specificity, increasing to 80% sensitivity and 96% specificity when combined with single item patient reported outcomes. Subject reported control over ejaculation and personal distress most strongly indicated premature ejaculation status. Partner personal distress was more influential in determining premature ejaculation status than estimated or measured intravaginal ejaculatory latency time, and single item measures were more influential than multiple item measures. Age was not influential in assigning premature ejaculation status. CONCLUSIONS: Neither self-estimated nor stopwatch measured intravaginal ejaculatory latency time alone was optimal for assigning premature ejaculation status. Subject and partner responses to single item measures, particularly control over ejaculation and personal distress, were important. Results suggest that a combination of estimated intravaginal ejaculatory latency time and the 4 single item patient reported outcome measures can adequately identify premature ejaculation status.

The psychological burden of premature ejaculation.

PURPOSE: Premature ejaculation is characterized by short ejaculatory latency, inability to control ejaculation and resultant overall decreased sexual satisfaction for the man and his partner. Diagnostic criteria typically include aspects of psychological well-being. To motivate and justify treatment for premature ejaculation a more comprehensive understanding of its impact on men, their partners and their overall relationship is needed. MATERIALS AND METHODS: In a community based, observational study of 1,587 men and their female partners clinicians diagnosed premature ejaculation using Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria. For purposes of this analysis this group was further restricted to subjects with a stopwatch measured intravaginal ejaculatory latency time of 2 minutes or less. Responses to the Premature Ejaculation Profile, Self-Esteem and Relationship questionnaire, Golombok-Rust Inventory of Sexual Satisfaction and Medical Outcomes Study SF-36 were compared between premature ejaculation and nonpremature ejaculation groups. Correlations between responses of men and partners were assessed for the Premature Ejaculation Profile and Golombok-Rust Inventory of Sexual Satisfaction. Correlations among patient reported measures enabled the assessment of independence of outcome variables. RESULTS AND CONCLUSIONS: Of 207 men who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria 89 had an intravaginal ejaculatory latency time of 2 minutes or less. Lower levels of sexual functioning and satisfaction, and higher levels of personal distress and interpersonal difficulty were reported by men with premature ejaculation and their partners. In addition, men with premature ejaculation rated their overall quality of life lower than that of men without premature ejaculation. Consequently premature ejaculation has a significant psychological burden on men, their partners and the male/partner relationship.

Cost-utility analysis of survival with epoetin-alfa versus placebo in stage IV breast cancer.

BACKGROUND: In a multinational trial of anaemic patients with cancer receiving nonplatinum-containing chemotherapy, epoetin-alfa effectively increased haemoglobin levels, reduced red blood cell transfusion requirements, and improved QOL. Although the study was not designed or powered to evaluate survival, a survival trend was noted favouring epoetin-alfa compared with placebo (median survival 17 vs 11 months [p = 0.126]). OBJECTIVES: To determine the incremental cost utility of epoetin-alfa versus placebo in anaemic patients with stage IV breast cancer from a UK National Health Service perspective. METHODS: Patient data regarding transfusions, epoetin-alfa usage, chemotherapy treatment cycles, and adverse events were recorded, with survival follow-up for 12-36 months post-study. Stage IV breast cancer therapy costs were collected by surveying UK oncologists, and utilities for associated health states were from published sources. Costs were in British pounds and year 2000 values. Costs and benefits were jointly determined for the stage IV breast cancer subgroup (n = 55). Incremental cost-utility ratios (ICURs) were calculated assuming a 6% annual discount rate for costs and a 1.5% annual discount rate for benefits. Bootstrap simulations (10,000 iterations) were conducted to account for uncertainty, and sensitivity analyses were conducted to establish robustness. RESULTS: The ICUR for epoetin-alfa treatment was pounds 8,851 per QALY, with a 99% probability of a positive net benefit in QALYs (net benefit = 0.4805 years of perfect life) and a 94% probability of being acceptable using a threshold ICUR of pounds 30,000/QALY. The main cost drivers distinguishing epoetin-alfa from placebo were the costs of drug and patient care due to increased survival. CONCLUSIONS: The available data suggest a high probability of favourable cost-utility outcomes with epoetin-alfa treatment for anaemia in patients with stage IV breast cancer receiving nonplatinum-containing chemotherapy. Additional studies are warranted.

The cost effectiveness of two new antiepileptic therapies in the absence of direct comparative data: a first approximation.

BACKGROUND: A number of new antiepileptic agents have been introduced within a short period of time. Direct comparisons are not available, and information about the balance between costs and effects for these new therapies is lacking. OBJECTIVE: To introduce a first approximation of the cost effectiveness of the new therapeutic agents (topiramate and lamotrigine) for epilepsy that have been assessed in clinical trials against placebo. METHODS: Without head to head comparative data no formal methods are available to assess the relative cost effectiveness of two products; therefore, a Bayesian approach was developed. The approach starts with the 'proportionality assumption' saying that the differences in healthcare expenditure (less the direct cost of therapy) are directly proportional to the differences in effectiveness. Given this assumption, a therapy that is x times as expensive as an alternative therapy has an equivalent cost-effectiveness profile if the acquisition cost is x times as high. Moreover, simple formulas can be derived to calculate the probabilities that a therapy is dominant (more effective and less expensive) and that it is weakly dominant (more effective and a better cost-effectiveness profile). The approach is applied to data from published fixed dosage, parallel-design studies comparing both topiramate and lamotrigine with placebo. RESULTS: Assuming that the 'proportionality assumption' holds for the medical treatment of epilepsy, and disregarding uncertainties, it is estimated that topiramate may be priced more than 2.2 times its current acquisition cost and still be more cost effective than lamotrigine. Taking uncertainties into account, it is estimated that lamotrigine 500 mg/day is dominated by topiramate 200 mg/day with a probability of 0.875 and by topiramate 400 mg/day with a probability of 0.986. CONCLUSIONS: A simple method can be applied to assess the relative cost effectiveness of two therapies in the absence of direct comparative data. Applying this method to compare topiramate and lamotrigine leads to a strong preference for topiramate. However, to be able to draw this conclusion, some heroic assumptions need to be made. As such the method as developed here only reflects a first approximation. It needs to be used with care and is not intended to replace good comparative research.

Epoetin alfa treatment results in clinically significant improvements in quality of life in anemic cancer patients when referenced to the general population.

PURPOSE: Anemia, highly common among cancer patients, is often an underlying cause of cancer-related fatigue and other quality-of-life (QOL) deficits. Although randomized clinical trials have shown that treatment with epoetin alfa increases hemoglobin levels, reduces fatigue, lessens transfusion requirements, and improves overall QOL, cancer-related anemia and fatigue remain undertreated. This is, in part, because scales and measures of QOL are still relatively unfamiliar to most clinicians and because population-based reference ranges are lacking, thus making clinical trial results difficult to interpret. METHODS: To aid in the interpretation of QOL results from clinical trials, we administered the Functional Assessment of Cancer Therapy-Anemia (FACT-An) QOL instrument to a nationally representative sample of 1,400 people using an Internet survey panel in the United States. We then compared the FACT-An data from the Internet survey with the QOL data of a 375-patient randomized, double-blind clinical trial evaluating epoetin alfa versus placebo in anemic cancer patients. RESULTS: FACT-An, as administered to the survey population, displayed good psychometric properties and was able to discriminate between respondents with histories of specified illnesses, including anemia and cancer, and those without. Comparison of the population norm and clinical trial data showed that treatment with epoetin alfa resulted in clinically meaningful as well as statistically significant improvements in QOL (P <.01). CONCLUSION: Reliable population norm data are now available to aid in the interpretation of clinical trial results where the FACT-An questionnaire is administered. In the clinical trial, treatment with epoetin alfa overcame much of the QOL deficit seen in anemic cancer patients compared with the norm population sample.

Development and validation of the Diabetic Foot Ulcer Scale-short form (DFS-SF).

BACKGROUND: The Diabetic Foot Ulcer Scale (DFS) provides comprehensive measurement of the impact of diabetic foot ulcers on patients' QOL through self-administration of 64 items comprising 15 subscales. OBJECTIVE: To develop and evaluate a short form of the DFS (DFS-SF) to reduce patient burden and the number of outcome measures, and to improve sensitivity to change in clinical condition. METHODS: The DFS-SF was created through the analysis of data from a double-blind, placebo-controlled, randomised trial of the efficacy and safety of becaplermin (recombinant human platelet-derived growth factor BB) in the treatment of chronic, full-thickness, neuropathic, diabetic foot ulcers. Using these data, items demonstrating poor psychometric properties were eliminated. Exploratory factor analyses were then conducted to develop a new, more parsimonious scaling algorithm that optimised the internal consistency of the new subscales. Finally, data from two additional clinical trials were used to assess replicability of the DFS-SF subscale structure. RESULTS: The DFS-SF contains a total of 29 items comprising six subscales. The results of both confirmatory and exploratory factor analyses provided support for the scaling algorithm. The DFS-SF subscales showed good internal consistency, reliability and construct validity, and demonstrated sensitivity to ulcer healing. CONCLUSIONS: The results of this investigation indicate that the DFS-SF has good psychometric properties and replicability.