United States Value Set for the Functional Assessment of Cancer Therapy-General Eight Dimensions (FACT-8D), a Cancer-Specific Preference-Based Quality of Life Instrument.

OBJECTIVES: To develop a value set reflecting the United States (US) general population's preferences for health states described by the Functional Assessment of Cancer Therapy (FACT) eight-dimensions preference-based multi-attribute utility instrument (FACT-8D), derived from the FACT-General cancer-specific health-related quality-of-life (HRQL) questionnaire. METHODS: A US online panel was quota-sampled to achieve a general population sample representative by sex, age (≥ 18 years), race and ethnicity. A discrete choice experiment (DCE) was used to value health states. The valuation task involved choosing between pairs of health states (choice-sets) described by varying levels of the FACT-8D HRQL dimensions and survival (life-years). The DCE included 100 choice-sets; each respondent was randomly allocated 16 choice-sets. Data were analysed using conditional logit regression parameterized to fit the quality-adjusted life-year framework, weighted for sociodemographic variables that were non-representative of the US general population. Preference weights were calculated as the ratio of HRQL-level coefficients to the survival coefficient. RESULTS: 2562 panel members opted in, 2462 (96%) completed at least one choice-set and 2357 (92%) completed 16 choice-sets. Pain and nausea were associated with the largest utility weights, work and sleep had more moderate utility weights, and sadness, worry and support had the smallest utility weights. Within dimensions, more severe HRQL levels were generally associated with larger weights. A preference-weighting algorithm to estimate US utilities from responses to the FACT-General questionnaire was generated. The worst health state's value was -0.33. CONCLUSIONS: This value set provides US population utilities for health states defined by the FACT-8D for use in evaluating oncology treatments.

The content validity of the PSS in patients with plaque psoriasis.

BACKGROUND: The primary objective of this study was to evaluate the content validity of the Psoriasis Symptom Scale (PSS), with a specific focus on understanding of the content of the PRO measure by conducting one-on-one interviews with patients with moderate to severe plaque psoriasis. This was a cross-sectional, qualitative study conducted with 20 patients with plaque psoriasis who participated in in-person, one-on-one interviews. Participants were asked to describe their psoriasis symptoms, completed the PSS, and were cognitively debriefed on its content. Interviews were conducted in two separate rounds. Following Round 1, the study data were examined to determine if modifications to the PSS were required. All interviews were audio-recorded and transcribed. Sociodemographic and clinical data were collected for sample descriptive purposes. RESULTS: The 20 study participants had a mean age of 50.2 ± 12.0 years (range: 25.0-73.0), and 55% were female. Thirty-five percent of the sample reported their psoriasis severity as moderate or severe. The average time since diagnosis of plaque psoriasis was almost 18 years, ranging from less than one to over 38 years. The most frequently reported symptoms and signs during the concept elicitation portion of the interviews included redness (N = 20, 100%), itching (n = 20, 100%), pain (n = 15, 75%), burning (n = 13, 65%), and flaking (n = 11, 55%). Overall, participants provided positive feedback on the PSS and felt that it was comprehensive and relevant to their experience with psoriasis. The item meaning and response options were well-understood for the majority of the items. Findings indicate that for the patient-reported symptom of redness, which is also a sign that can be reported by clinicians, redness or the perception of redness is most accurately captured by patient report. Study results did not support modifications to the instrument and no changes to the PSS were recommended. CONCLUSION: The evidence gained in this study provided support for the content validity of the PSS for use as clinical trial endpoint among patients with plaque psoriasis. This study found that the symptoms included in the PSS are important to and well-understood by patients with plaque psoriasis. The PSS is appropriate for inclusion in future studies designed to measure the effect of treatment on psoriasis-related symptoms.

Impact of brodalumab treatment on psoriasis symptoms and health-related quality of life: use of a novel patient-reported outcome measure, the Psoriasis Symptom Inventory.

BACKGROUND: Psoriasis symptoms have a significant negative impact on health-related quality of life, impairing physical functioning and well-being. OBJECTIVE: To evaluate the impact of brodalumab, a human anti-interleukin-17R monoclonal antibody, on psoriasis symptom severity as measured by a novel patient-reported outcome measure, the Psoriasis Symptom Inventory, and dermatology-specific health-related quality of life as measured by the Dermatology Life Quality Index (DLQI). METHODS: This was a secondary analysis of a phase II, randomized, double-blind, placebo-controlled clinical study of patients with moderate-to-severe psoriasis (n = 198) treated with brodalumab or placebo. This analysis assessed Psoriasis Symptom Inventory scores and DLQI scores over time. Analyses were conducted on all patients who were randomized and received one or more injections of the study drug according to intention to treat using last observation carried forward to impute missing data. RESULTS: At week 12, subjects in the brodalumab groups had significant improvements in mean Psoriasis Symptom Inventory total scores [8.5 (70 mg), 15.8 (140 mg), 16.2 (210 mg) and 12.7 (280 mg)] compared with placebo (4.8). Mean improvements in DLQI were clinically meaningful (≥ 5.7) in the brodalumab groups (6.2, 9.1, 9.6 and 7.1, respectively) and significantly greater than placebo (3.1). Improvements in Psoriasis Symptom Inventory were observed as early as week 2 and in DLQI by week 4. All eight Psoriasis Symptom Inventory item scores improved significantly among the brodalumab groups by week 12. CONCLUSIONS: Results were from a single randomized clinical trial and may not generalize to broader patient populations. However, treatment with brodalumab provided significant improvement in psoriasis symptoms in patients with moderate-to-severe psoriasis.

Evaluating symptom outcomes in gastroparesis clinical trials: validity and responsiveness of the Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD).

BACKGROUND: Patient-reported symptom scales are needed to evaluate treatments for gastroparesis. The Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) was developed to assess daily symptoms of gastroparesis. This study evaluated the validity and responsiveness of the GCSI-DD in patients with gastroparesis. METHODS: Symptomatic patients were started with a new treatment for gastroparesis. Patients completed the GCSI-DD each evening during a baseline week and for 8 weeks of treatment. Responders were defined based on patient and clinician global rating of change. Minimal important differences (MID) were estimated based on baseline to 4 week changes in symptoms scores for small improvements. KEY RESULTS: Of 69 patients participating, 46 had idiopathic, 19 diabetic, and four postfundoplication gastroparesis. Excellent test-retest reliability was seen for GCSI-DD scores, and there were significant correlations between GCSI-DD scores and clinician ratings of symptom severity. Responders to treatment reported improvements in nausea [effect size (ES) = 0.42, P < 0.001], postprandial fullness, ES = 0.83, P < 0.001), bloating (ES = 0.34, P < 0.001), early satiety (ES = 0.53, P < 0.001), but lower responses for upper abdominal pain (ES = 0.29), and vomiting (ES = 0.22; P = 0.119). MIDs were 0.55 for nausea, 0.97 for excessive fullness, 0.63 for bloating, 0.77 for postprandial fullness, and 0.30 for abdominal pain. A composite score of four symptoms (Composite-1; nausea, bloating, excessive fullness, postprandial fullness) had ES of 0.61 and MID of 0.73. Composite-2 score (nausea, early satiety, bloating, abdominal pain) had a lower ES of 0.47. CONCLUSIONS & INFERENCES: Symptoms of early satiety, nausea, postprandial fullness, and bloating were responsive to treatment for gastroparesis. A composite of these symptoms also demonstrates validity and responsiveness to treatment for gastroparesis, and may represent an acceptable endpoint for evaluating the effectiveness of medical treatments in clinical trials for gastroparesis.

PROMIS computerised adaptive tests are dynamic instruments to measure health-related quality of life in patients with cirrhosis.

BACKGROUND: Cirrhotic patients have an impaired health-related quality of life (HRQOL), which is usually analysed using static paper-pencil questionnaires. The Patient Reported Outcomes Measurement Information System (PROMIS) computerised adaptive testing (CAT) are flexible, freely available, noncopyrighted, HRQOL instruments with US-based norms across 11 domains. CAT presents five to seven questions/domain depending on the patient's response, from large validated question banks. This provides brevity and precision equivalent to the entire question bank. AIM: To evaluate PROMIS CAT tools against 'legacy instruments' for cirrhotics and their informal caregivers. METHODS: A total of 200 subjects: 100 cirrhotics (70 men, 53% decompensated) and 100 caregivers were administered the PROMIS and legacy instruments [Sickness Impact Profile (SIP), Beck depression/anxiety inventories, Pittsburgh Sleep-Quality Index (PSQI) and Epworth Sleepiness scale (ESS)] concurrently. Both legacy and PROMIS results for patients were compared with caregivers and US norms. These were also compared between compensated and decompensated patients. Preference for SIP or PROMIS was inquired of a selected group (n = 70, 50% patients). Test - retest reliability was assessed in another group of 20 patients. RESULTS: Patients had significant impairment on all PROMIS domains apart from anger and anxiety compared with caregivers and US norms (P < 0.02 to <0.0001). Decompensated patients had significantly worse sleep, pain, social and physical function scores compared with compensated ones, similar to legacy instruments. There was a statistically significant correlation between PROMIS and their corresponding legacy instruments. The majority (71%) preferred PROMIS over SIP. PROMIS tools had significant test - retest reliability (ICC range 0.759-0.985) when administered 12 ± 6 days apart. CONCLUSION: PROMIS computerised adaptive testing tools had significant concurrent and discriminant validity, test - retest reliability and subject preference for assessing HRQOL in cirrhotic patients.

The development and validation of a Nocturnal Gastro-oesophageal Reflux Disease Symptom Severity and Impact Questionnaire for adults.

BACKGROUND: Current questionnaires for assessing gastro-oesophageal reflux disease (GERD) symptoms are limited in their ability to capture nocturnal symptoms. AIM: To develop and validate an instrument, the Nocturnal Gastro-oesophageal Reflux Disease Symptom Severity and Impact Questionnaire (N-GSSIQ), to assess severity and impact of nocturnal GERD symptoms. METHODS: Two focus groups and 16 cognitive debriefing interviews were conducted among GERD patients to identify key issues about nocturnal symptoms. A draft instrument was tested in 196 patients at 11 clinics in the US to evaluate psychometric properties. Exploratory factor and item response theory analyses were conducted to finalize items and subscales. Internal consistency reliability, reproducibility and construct validity were examined. RESULTS: Mean age was 45 (s.d. = 13.8) years; 76% were female and 68% were Caucasian. Patient-rated severity was mild-moderate for 69% of participants; 48% reported symptoms on two to three nights the past week. The final questionnaire includes 20 items and three subscales: Nocturnal GERD Symptoms, Morning Impact of Nocturnal GERD and Concern about Nocturnal GERD. The subscales demonstrated internal consistency reliability (Cronbach's alpha 0.84-0.94) and were significantly correlated with similar measures and disease severity (0.41-0.81; P < 0.0001). CONCLUSION: The results support the reliability and validity of the N-GSSIQ as a measure of severity, morning impact and concern about nocturnal GERD.

Development and content validity of a gastroparesis cardinal symptom index daily diary.

BACKGROUND: The Gastroparesis Cardinal Symptom Index (GCSI) is a patient-reported outcome for gastroparesis using a two-week recall period. To minimize potential patient recall effects, a daily diary version of the GCSI (GCSI-DD) was developed. AIMS: To evaluate the content validity of GCSI-DD for the symptoms in patients with documented gastroparesis, to capture symptom variability over time and to compare responses of this GCSI-DD to the original GCSI. METHODS: In gastroparesis adults with delayed gastric emptying, cognitive debriefing interviews were conducted to elicit their perspective on relevant symptoms of gastroparesis and relevant recall periods and to evaluate patient understanding of GCSI-DD. Patients completed the GCSI-DD daily over a 2-week period and completed the GCSI at baseline and the 2-week follow-up visit. RESULTS: Twelve gastroparesis patients, of whom five were diabetic and nine women, reported nausea (100%), vomiting (100%), stomach fullness (75%), bloating (58%) and loss of appetite (50%) were important symptoms. All patients understood diary instructions and item content and reported that the diary captured their gastroparesis symptom experience; 83% considered response scales adequate. There was significant daily variability in GCSI-DD scores. Mean GCSI-DD subscale and total scores over 2 weeks correlated strongly (all r > 0.90) with GCSI scores at 2-week follow-up. CONCLUSIONS: The GCSI-DD includes symptoms relevant to patients with gastroparesis, captures daily variability of those symptoms and has psychometric properties consistent with a good patient-reported outcome endpoint for gastroparesis clinical trials.

Validation of the revised Patient Perception of Migraine Questionnaire (PPMQ-R): measuring satisfaction with acute migraine treatment in clinical trials.

This study was aimed to evaluate in clinical trial settings the psychometric properties of the revised Patient Perception of Migraine Questionnaire (PPMQ-R), a satisfaction measure for acute migraine treatment. The PPMQ-R was administered 24 h post dosing in 1304 migraineurs randomized to two identical Phase 3, single-attack trials. Reliability, concurrent and construct validity and known-groups validity were evaluated using Cronbach's alpha, Pearson correlations and analysis of variance, respectively. PPMQ-R scale and Total scores (Efficacy, Functionality and Ease of use) showed very good internal consistency reliability (alpha 0.84-0.99). Efficacy, Functionality and Total PPMQ-R scores showed large, inverse relationships with migraine pain severity, number of migraine symptoms and work ability (r = -0.62 to -0.75; all P < 0.0001). All scales discriminated among migraine pain severity levels (all P < 0.001). The PPMQ-R has sufficient evidence of validity and reliability for measuring patient satisfaction, an important benchmark of quality and effective care.

The impact of measuring patient-reported outcomes in clinical practice: a systematic review of the literature.

OBJECTIVE: The purpose of this paper is to summarize the best evidence regarding the impact of providing patient-reported outcomes (PRO) information to health care professionals in daily clinical practice. METHODS: Systematic review of randomized clinical trials (Medline, Cochrane Library; reference lists of previous systematic reviews; and requests to authors and experts in the field). RESULTS: Out of 1,861 identified references published between 1978 and 2007, 34 articles corresponding to 28 original studies proved eligible. Most trials (19) were conducted in primary care settings performed in the USA (21) and assessed adult patients (25). Information provided to professionals included generic health status (10), mental health (14), and other (6). Most studies suffered from methodologic limitations, including analysis that did not correspond with the unit of allocation. In most trials, the impact of PRO was limited. Fifteen of 23 studies (65%) measuring process of care observed at least one significant result favoring the intervention, as did eight of 17 (47%) that measured outcomes of care. CONCLUSIONS: Methodological concerns limit the strength of inference regarding the impact of providing PRO information to clinicians. Results suggest great heterogeneity of impact; contexts and interventions that will yield important benefits remain to be clearly defined.

Measuring validity of self-reported symptoms among people with HIV.

Symptoms are important indicators of health and treatment for people with HIV. Symptoms are measured by patient self-report, but there has been little attention to what is the best method of elicitation. We compared three methods (presence, frequency, and bother) commonly used to measure HIV self-reported symptoms. CD4+ T lymphocyte count and health-related quality of life (HRQL) scales were used to test validity in 160 people with HIV. The average number of symptoms reported was 15.2 (standard deviation 8.4). Correlation coefficients of summary symptom scores using the three methods ranged from -0.30 to -0.36 with HRQL score and from -0.19 to -0.20 with CD4 count (p<0.05). Correlation coefficients of seven specific symptom items with CD4+ counts and HRQL scores for the same concepts were small to moderate (-0.08 to -0.58, p<0.05). For the three methods, the correlation coefficients in general tended to be greater with frequency or bother than presence. However, the differences among the three methods were not statistically significant. We conclude that no single method is superior to the others.

Patient assessment of treatment satisfaction: methods and practical issues.

Measurement of treatment satisfaction in gastro-oesophageal reflux disease (GORD) is compromised by an insufficient conceptual foundation and poor assessment methods. The current state of the art in measuring treatment satisfaction is incomplete, and the existing measurement is insufficient. Here, the definition, conceptualisation, application, and methodological issues associated with measurement of treatment satisfaction in GORD are reviewed. Treatment satisfaction may be important for differentiating among GORD treatments, and for monitoring patient outcomes in clinical practice.

Development and psychometric evaluation of the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) in patients with upper gastrointestinal disorders.

OBJECTIVE: Describe the development and evaluation of a new self-report instrument, the patient assessment of upper gastrointestinal disorders-symptom severity index (PAGI-SYM) in subjects with gastroesophageal reflux disease (GERD), dyspepsia, or gastroparesis. METHODS: Recruited subjects with GERD (n=810), dyspepsia (n = 767), or gastroparesis (n = 169) from the US, France, Germany, Italy, the Netherlands, and Poland. Subjects completed the PAGI-SYM, SF-36, a disease-specific HRQL measure (PAGI-QOL), and disability day questions. Two-week reproducibility was evaluated in 277 stable subjects. We evaluated construct validity by correlating subscale scores with SF-36, PAGI-QOL, disability days, and global symptom severity scores. RESULTS: The final 20-item PAGI-SYM has six subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain. Internal consistency reliability was good (alpha = 0.79-0.91); test-retest reliability was acceptable (Intraclass correlation coefficients alpha=0.60-0.82). PAGI-SYM subscale scores correlated significantly with SF-36 scores (all p < 0.0001), PAGI-QOL scores (all p < 0.0001), disability days (p < 0.0001), and global symptom severity (p < 0.0001). Mean PAGI-SYM scores varied significantly in groups defined by disability days (all p < 0.0001), where greater symptom severity was associated with more disability days. CONCLUSIONS: Results suggest the PAGI-SYM, a brief symptom severity instrument, has good reliability and evidence supporting construct validity in subjects with GERD, dyspepsia, or gastroparesis.

Development and validation of a patient-assessed gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index.

BACKGROUND: Patient-based symptom assessments are necessary to evaluate the effectiveness of medical treatments for gastroparesis. AIM: To summarize the development and measurement qualities of the Gastroparesis Cardinal Symptom Index (GCSI), a new measure of gastroparesis-related symptoms. METHODS: The GCSI was based on reviews of the medical literature, clinician interviews and patient focus groups. The measurement qualities (i.e. reliability, validity) of the GCSI were examined in 169 gastroparesis patients. Patients were recruited from seven clinical centres in the USA to participate in this observational study. Patients completed the GCSI, SF-36 Health Survey and disability day questions at a baseline visit and again after 8 weeks. Clinicians independently rated the severity of the patients' symptoms, and both clinicians and patients rated the change in gastroparesis-related symptoms over the 8-week study. RESULTS: The GCSI consists of three sub-scales: post-prandial fullness/early satiety, nausea/vomiting and bloating. The internal consistency reliability was 0.84 and the test-re-test reliability was 0.76 for the GCSI total score. Significant relationships were observed between the clinician-assessed symptom severity and the GCSI total score, and significant associations were found between the GCSI scores and SF-36 physical and mental component summary scores and restricted activity and bed disability days. Patients with greater symptom severity, as rated by clinicians, reported greater symptom severity on the GCSI. The GCSI total scores were responsive to changes in overall gastroparesis symptoms as assessed by clinicians (P = 0.0002) and patients (P = 0.002). CONCLUSION: The findings of this study indicate that the GCSI is a reliable and valid instrument for measuring the symptom severity in patients with gastroparesis.

Validity and responsiveness of the euroqol as a measure of health-related quality of life in people enrolled in an AIDS clinical trial.

OBJECTIVE: Brief utility measures are needed in clinical trials in addition to existing descriptive measures of health-related quality of life (HRQOL). We examined the reliability and validity of the EuroQol (EQ-SD) and MOS-HIV and their responsiveness to HIV-related clinical events. METHODS: Subjects with advanced HIV disease (CD4 < 100) were enrolled in a randomized trial for CMV prophylaxis (n = 990). The EQ-5D includes a weighted sum of five domains (EQ-5D Index) and a visual analog scale (EQ-VAS). The MOS-HIV has 10 subscales and physical (PHS) and mental health summary scores (MHS). Construct validity of the EQ-5D was tested based on hypothesized relationships to subscales of the MOS-HIV. Relative precision and responsiveness to adverse experiences and opportunistic infections (Ols) were compared for the two instruments. RESULTS: Mean age of the patients was 38, 94% were male, 80% white, and 7% had injected drugs. Mean baseline scores for EQ-5D Index and EQ-VAS were 0.80 and 76.0, respectively, 28 and 4% reported maximum scores. Mean MOS-HIV subscales score ranged from 55 (role) to 84 (cognitive); mean PHS and MHS were 47.4 and 49.5, respectively. Correlations between MOS-HIV subscales and EQ-5D Index ranged from 0.45 (role) to 0.63 (pain); correlations with EQ-VAS ranged from 0.33 (cognitive) to 0.66 (health perceptions). Correlations between MOS-HIV PHS and MHS with EQ-5D Index were 0.61 and 0.58; and with EQ-VAS, 0.57 and 0.60, respectively. Responsiveness to adverse experiences was highest for MOS-HIV pain and PHS (effect sizes = 0.9 and 0.4); pain had the highest relative precision (2.4) for adverse experiences: EQ-VAS had the greatest relative precision (1.6) for developing an OI. CONCLUSION: In these patients with advanced HIV disease. EQ-5D showed good construct validity, but there may be a ceiling effect for its EQ-5D Index component. EQ-5D was less responsive to adverse events than the MOS-HIV. However, the EQ-VAS was most sensitive to developing an OI and is likely to be a useful measure of HRQOL for generating QALYs in cost-utility studies involving patients with advanced HIV disease.

Cost effectiveness of the newer atypical antipsychotics: a review of the pharmacoeconomic research evidence.

A comprehensive evaluation of atypical antipsychotics for the treatment of schizophrenia involves documentation of clinical effectiveness, quality of life and medical cost outcomes. The results of pharmacoeconomic studies assist psychiatrists, and other healthcare decision-makers, in identifying pharmacotherapies that provide the greatest benefit to patients at the most acceptable cost. The cost-effectiveness of the newer atypical antipsychotics has been examined using clinical decision-modeling studies and randomized clinical trials. The research evidence suggests that clozapine is a cost-effective treatment for neuroleptic refractory schizophrenia. Olanzapine and risperidone may be cost-neutral or, at best, slightly cost-saving compared with conventional antipsychotics, although they do improve clinical symptoms and quality of life outcomes. There is insufficient published data on pharmacoeconomic outcomes for sertindole, quetiapine and ziprasidone to make any conclusions about their cost-effectiveness in treating schizophrenia.

The economics of selective serotonin reuptake inhibitors in depression: a critical review.

The prevalence of depression and the high costs associated with its treatment have increased interest in pharmacoeconomic evaluations of drug treatment, particularly in the 1990s as the use of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) expanded substantially. This review presents results from specific studies representing the key study designs used to address the pharmacoeconomics of SSRI use: retrospective administrative database analyses, clinical decision analysis models, and randomised clinical trials. Methodological considerations in interpreting results are highlighted. In retrospective administrative database analyses, most comparisons have been made between SSRIs and tricyclic antidepressants (TCAs). A few studies have addressed differences between SSRIs. The studies focused on healthcare cost (to payer) and cost-related outcomes (e.g. treatment duration, drug switching). Although SSRIs are generally associated with higher drug acquisition costs than are TCAs, total healthcare costs are at least offset, if not decreased, by reductions in costs associated with use of SSRIs. Although studies from the early 1990s show some advantage for fluoxetine, the results are limited by use of data from shortly after the introduction of paroxetine and sertraline; studies from the mid- 1990s on that compare drugs within the SSRI class show general equivalence in terms of cost. Important methodological advances are occurring in retrospective studies, with selection bias and other design limitations being addressed statistically. Clinical decision analysis models permit flexibility in terms of ability to specify different alternative treatment scenarios and varying durations. Sensitivity analysis aids interpretability, although model inputs are limited by data availability. Results from short term (1 year duration or less) studies comparing SSRIs and TCAs suggest that SSRIs are more cost effective or that there is no difference. Longer term studies (lifetime Markov models) focus more on the impact of maintenance antidepressant therapy and show more mixed results, generally favouring SSRIs over TCAs. The results indicate that the effect of SSRIs is mainly through prevention of relapse. Important assumptions of these models include fewer serious adverse effects and lower treatment discontinuation rates with SSRIs. Naturalistic clinical trials provide greater generalisability than traditional randomised clinical trials. One naturalistic trial found that nearly half of TCA-treated patients switched to another antidepressant within 6 months; only 20% of SSRI-treated patients switched. Cost differences between groups were minimal. These studies indicate few differences in medical costs, depression outcomes and health-related quality of life between TCAs and fluoxetine, although fewer fluoxetine-treated patients switched treatment.

Symptom and health-related quality-of-life measures for use in selected gastrointestinal disease studies: a review and synthesis of the literature.

Patient-rated symptom and health-related quality-of-life (HR-QOL) outcomes are important end-points for clinical trials of medical treatments for gastrointestinal (GI) disorders. Based on this review, patient outcomes research is focused on gastroesophageal reflux disease and dyspepsia, with a growing interest in irritable bowel syndrome but little research in gastroparesis. State-of-the-art for patient-rated symptom scales is rudimentary with an abundance of scales and little attention to systematic instrument development or comprehensive psychometric evaluation. Generally, disease-specific HR-QOL measures have been more systematically developed and evaluated psychometrically, but few have been incorporated into clinical trials. More comprehensive outcome assessments are needed to determine the effectiveness of new medical treatments for functional GI disorders. Future clinical trials of GI disorders should combine clinician assessments of outcomes and symptoms with patient-rated symptom and HR-QOL end-points.

Imputing physical health status scores missing owing to mortality: results of a simulation comparing multiple techniques.

BACKGROUND: Having missing data complicates the statistical analysis of health-related quality-of-life (HRQOL) data and, depending on the extent and nature of missing data, can introduce significant bias in treatment comparisons. OBJECTIVE: We evaluated the bias associated with 4 different imputation methods for estimating physical health status (PHS) scores missing as a result of mortality. METHODS: A simulation study was conducted in which we systematically varied mortality rates from 0% to 30% and change in PHS scores from -20 to 20 on a 100-point scale for a 2-group clinical trial with follow-up over 18 months. The 4 imputation methods were last value carried forward (LVCF), arbitrary substitution (ARBSUB), empirical Bayes (BAYES), and within-subject modeling (WSMOD). Pseudo-root mean square residuals (RMSRs) and differences between true and estimated slopes were used to evaluate how well the imputation methods reproduced the true characteristics of the simulated population data. RESULTS: ARBSUB and BAYES methods have the smallest RMSRs compared with LVCF and WSMOD across all mortality rates. As the rate of missing data resulting from mortality increased, all imputation techniques deviated more from population data. The BAYES technique was best at reproducing group slopes in cases with differential mortality rates or when mortality rates exceeded 15%. WSMOD and LVCF significantly underestimated changes in PHS. CONCLUSIONS: The different imputation methods produced comparable results when there were few missing data. The BAYES approach most closely estimated true population differences and change in PHS regardless of missing data rates. These findings are limited to physical health and functioning measures.

Functional outcomes in schizophrenia: a comparison of olanzapine and haloperidol in a European sample.

The primary aim of this study was to compare functional outcomes between patients with schizophrenia treated with olanzapine or haloperidol in Europe. The sample consisted of European patients from a large, international, double-blind, randomized clinical trial. Patients were randomized to receive either olanzapine (n = 520) or haloperidol (n = 258) for a 6-week acute phase followed by a 46-week maintenance phase for responders. Olanzapine-treated patients experienced superior improvements compared to haloperidol-treated patients on all efficacy measures assessed in both phases. A greater percentage of olanzapine-treated patients had > or = 20% improvement in the Quality of Life Scale total score during both the acute (50.0% versus 31.0%, P = 0.071) and maintenance (69.5% versus 41.7%, P = 0.006) phases compared to haloperidol-treated patients. For patients who entered the maintenance phase as outpatients, olanzapine-treated patients were significantly less likely to require subsequent hospitalization compared to haloperidol-treated patients (P = 0.001). A significantly greater percentage of the olanzapine group compared to the haloperidol group worked part-time or full-time (15.1% versus 5.3%, P = 0.018), participated in useful work > or = 75% of the time (21.0% versus 10.5%, P = 0.038), and socialized more than once a month (53.8% versus 37.9%, P = 0.004) during the maintenance phase. The findings from this study suggest that olanzapine's clinical profile leads to reduced hospitalization and improvements in work and social functioning superior to that achieved with haloperidol treatment.

Effectiveness and costs of omeprazole vs ranitidine for treatment of symptomatic gastroesophageal reflux disease in primary care clinics in West Virginia.

OBJECTIVE: To compare clinical, health-related quality of life (HRQL), and medical cost outcomes in patients with symptomatic gastroesophageal reflux disease (GERD) receiving omeprazole sodium or ranitidine hydrochloride treatment. METHODS: A multicenter, randomized, open-label, medical effectiveness trial conducted in 5 university-based family medicine clinics. Two hundred sixty-eight patients with GERD were recruited and randomly assigned to omeprazole sodium, 20 mg once daily, or ranitidine hydrochloride, 150 mg twice daily, for up to 6 months. Main outcome assessments included the Gastrointestinal Symptom Rating Scale (GSRS) Reflux score, Psychological General Well-Being Index, and Short-Form-36 Health Survey administered at baseline and 2, 4, 12, and 24 weeks. Medical resource use and cost data were collected. RESULTS: More omeprazole-treated patients reported improved heartburn resolution at 2 weeks (49.0% vs 33.3%; P=.007) and 4 weeks (58.6% vs 35.0%; P<.001) compared with ranitidine-treated patients. The GSRS Reflux scores across 3 months showed overall differences between omeprazole (mean, 2.67) and ranitidine (mean, 2.95) groups (P=.04). Mean total 6-month medical costs were $915 lower ($8371 vs $9286; P=.64), and no difference in mean outpatient medical costs ($1198 vs $1158; P=.76) were observed in the omeprazole group compared with the ranitidine group. A post hoc secondary analysis showed that, at 12 and 24 weeks, patients treated with omeprazole for 8 weeks or more reported greater heartburn resolution (ie, 24 [43%] of 56 patients at both intervals) than patients treated with ranitidine for 8 weeks or more (12 [24%] and 13 [26%] of 50 patients, respectively; P=.001). CONCLUSIONS: Ranitidine and omeprazole were both effective at improving heartburn symptoms; however, omeprazole provided greater resolution of heartburn symptoms at 2 and 4 weeks. Despite omeprazole's higher acquisition cost, there were no significant differences in total or outpatient costs between groups.