Health and Quality of Life Outcomes - Latest Articles

Potential of patient-reported outcomes as nonprimary endpoints in clinical trials

Ari Gnanasakthy — 2013-05-15T00:00:00Z

Background: The purpose of this research was to fully explore the impact of endpoint type (primary vs. nonprimary) on decisions related to patient-reported outcome (PRO) labeling claims supported by PRO measures and to determine if nonprimary PRO endpoints are being fully optimized based on more than 12 years of data.This review examines the use of PROs as both primary and nonprimary endpoints in support of demonstration of treatment benefit of new molecular entities (NMEs) and biologic license applications (BLAs) in the United States in the years 2000 to 2012. Methods: All NMEs and BLAs approved by the Food and Drug Administration (FDA) between January 2000 and June 2012 were identified using the FDA Drug Approval Reports Web page. Generic products granted tentative approvals were excluded. For all identified products, medical review sections from publicly available drug approval packages were reviewed to identify PRO endpoint status. Product labels (indication, clinical trials sections) were reviewed to determine the number and type of PRO claim. Results: A total of 308 NMEs/BLAs were identified. Of these, 70 NMEs/BLAs (23%) were granted PRO claims. The majority of product claims were for disease- or condition-specific signs and symptoms. Of the 70 products with PRO claims, a PRO was a primary endpoint for the vast majority (57 [81%]). A total of 19 of the 70 products were granted a PRO claim based on a nonprimary endpoint. While nonprimary endpoints were used most often to support claims of improved signs or symptoms, nonprimary endpoints were much more likely to support claims of higher order impacts. Conclusions: Successful PRO labeling claims are typically based on primary endpoints assessing signs and symptoms. Based on this research, studies with PROs as primary endpoints are far more likely to facilitate positive regulatory review and acceptance of PROs in support of labeling claims. Although inclusion of PROs as nonprimary endpoints in clinical trials has its challenges, recent PRO labels granted by the FDA show that they can indeed be candidates for PRO labeling claims as long as they are supported by evidence.

Improvements in patient-reported outcomes with apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of moderate to severe psoriasis: results from a phase IIb randomized, controlled study

Vibeke Strand — 2013-05-10T00:00:00Z

Background: Apremilast, a specific inhibitor of phosphodiesterase 4, modulates pro-inflammatory and anti-inflammatory cytokine production.Objectives: Apremilast's effect on patient-reported outcomes (PROs) in patients with moderate to severe psoriasis was evaluated in a phase IIb randomized controlled trial (NCT00773734). Methods: In this 16-week, placebo-controlled study, 352 patients with moderate to severe plaque psoriasis received placebo or apremilast (10, 20, or 30 mg BID). PROs included Dermatology Life Quality Index (DLQI), pruritus visual analog scale (VAS), and Short-Form Health Survey (SF-36) to assess health-related quality of life (HRQOL). Changes from baseline and patients reporting improvements >=minimum clinically important differences (MCID) were analyzed. Correlations between changes across various PRO instruments were explored. Results: Baseline DLQI (>10 points) and SF-36 MCS and domain scores indicated impairments in HRQOL. At 16 weeks, greater improvements from baseline in DLQI scores were reported with apremilast 20 (-5.9) and 30 mg BID (-4.4) compared with placebo (1.9; P<=0.005 for both), and a greater proportion of patients reported improvements >=MCID (20 mg BID, 49.4%, 30 mg BID, 44.3%) versus placebo (25.0%; P<0.04). Greater improvements from baseline in pruritus VAS scores were reported with apremilast 20 (-35.5%) and 30 mg BID (-43.7%) versus placebo (-6.1%; P<=0.005). Significant and clinically meaningful improvements in SF-36 mental component summary scores (P<=0.008) and Bodily Pain, Mental Health, and Role-Emotional domains were reported with all apremilast doses (P<0.05), and Social Functioning with 20 and 30 mg BID (P<0.05) and Physical Functioning with 20 mg BID (P<0.03). Correlations between SF-36 scores and DLQI were moderate (r>0.30 and <=0.60) and low between SF-36 and pruritus VAS (r<=0.30), indicating they measure different aspects of the disease. Conclusions: Apremilast treatment resulted in improved HRQOL, including DLQI and pruritus VAS over 16 weeks of treatment, in patients with moderate to severe psoriasis.

A comparison of four different approaches to measuring health utility in depressed patients

Nicholas Turner — 2013-05-09T00:00:00Z

Background: A variety of instruments are used to measure health related quality of life. Few data exist on the performance and agreement of different instruments in a depressed population. The aim of this study was to investigate agreement between, and suitability of, the EQ-5D-3L, EQ-5D Visual Analogue Scale (EQ-5D VAS), SF-6D and SF-12 new algorithm for measuring health utility in depressed patients. Methods: The intraclass correlation coefficient (ICC) and Bland and Altman approaches were used to assess agreement. Instrument sensitivity was analysed by: (1) plotting utility scores for the instruments against one another; (2) correlating utility scores and depressive symptoms (Beck Depression Inventory (BDI)); and (3) using Tukey's procedure. Receiver Operating Characteristic (ROC) analysis assessed instrument responsiveness to change. Acceptability was assessed by comparing instrument completion rates. Results: The overall ICC was 0.57. Bland and Altman plots showed wide limits of agreement for each pair wise comparison, except between the SF-6D and SF-12 new algorithm. Plots of utility scores displayed 'ceiling effects' in the EQ-5D-3L index and 'floor effects' in the SF-6D and SF-12 new algorithm. All instruments showed a negative monotonic relationship with BDI, but the EQ-5D-3L index and EQ-5D VAS could not differentiate between depression severity sub-groups. The SF-based instruments were better able to detect changes in health state over time. There was no difference in completion rates of the four instruments. Conclusions: There was a lack of agreement between utility scores generated by the different instruments. According to the criteria of sensitivity, responsiveness and acceptability that we applied, the SF-6D and SF-12 may be more suitable for the measurement of health related utility in a depressed population than the EQ-5D-3L, which is the instrument currently recommended by NICE.

Development of salutogenetic factors in mental health - Antonovsky's sense of coherence and Bandura's self-efficacy related to Derogatis' symptom check list (SCL-90-R)

Henrik Kröninger-Jungaberle — 2013-05-08T00:00:00Z

Background: The paper analyses how resilience factors and mental health problems interrelate in a 3-year-longitudinal study with 16–19 year olds. Methods: Resilience was measured with a 13-item short version of the Life-Orientation-Scale by Antonovsky (sense-of-coherence, SOC) and a 10-item self-efficacy-scale (SWE) by Jerusalem and Schwarzer. Mental health problems were measured with Derogatis Symptom Check list (SCL-90-R). The data set included 155 participants and was analyzed using Structural Equation Modeling (SEM) designed to examine mutual influence in longitudinal data with Mplus software. Results: The descriptive data analysis indicates (1) negative correlations between SOC and SCL-90-R at both age 16 and 19 in all subscales but somatization and likewise (2) between self-efficacy and SCL-90-R. (3) SOC correlates positively with SWE at age 16 and 19.Results of SEM analysis were based on the assumption of two latent variables at two points in time: resilience as measured with mean SOC and mean self-efficacy scores and health problems measured with sub scale scores of SCL-90-R – both at ages 16 and 19. The first SEM model included all possible paths between the two latent variables across time. We found (4) that resilience influences mental health problems cross-sectionally at age 16 and at age 19 but not across time. (5) Both resilience and mental health problems influenced their own development over time. A respecified SEM model included only significant paths. (6) Resilience at age 16 significantly influences health problems at age 16 as well as resilience at age 19. Health problems at age 16 influence those at age 19 and resilience at age 19 influences health problems at age 19. Conclusion: (a) SOC and self-efficacy instruments measure similar phenomena. (b) Since an influence of resilience on mental health problems and vice versa over time could not be shown there must be additional factors important to development. (c) SOC and self-efficacy are both very stable at 16 and 19 years. This refutes Antonovsky’s assumption that SOC achieves stability first around the age of 30. SOC and self-efficacy are protective factors but they seem to form in (early) childhood.

Psychometric evaluation of a Swedish version of Minneapolis-Manchester quality of life-youth form and adolescent form

Eva-Lena Einberg — 2013-05-08T00:00:00Z

Background: It has become important to measure long-term effects and quality of life in survivors of childhood cancer. The Minneapolis- Manchester Quality of Life (MMQL) instrument has been proven to better capture the quality of life (QoL) perspective of health than other instruments. The instrument has age appropriate versions and is therefore favourable for longitudinal studies of QoL of children surviving from cancer. The aim of this study was to evaluate the psychometric properties of the Swedish version of MMQL-Youth Form and the Adolescent Form focusing on: 1) face and content validity 2) the internal consistency and 3) the test-retest reliability. Methods: The sample consisted of 950 pupils (11–16 years old) from 7 schools in the western Sweden who completed the questionnaire. For the test-retest evaluation 230 respondents completed the questionnaire two weeks later. Results: Face and content validity was supported and internal consistency was found to be acceptable for the total scale for both the MMQL-Youth Form (8–12 years of age) and the Adolescent Form (13–20 years of age). Test-retest reliability for the MMQL-Youth Form was moderate for 50% of the items and good for the remaining. For the MMQL-Adolescent Form the test-retest showed moderate or good agreement for 80% of the items and fair for 20%. Conclusions: The result indicated that the Swedish version of the MMQLYouth Form and Adolescent Form was valid and reliable in a sample of healthy children in a Swedish context. It is recommended to test the instrument among diverse samples of children such as survivors of childhood cancer in order to validate its usefulness in research and clinical settings.

The development and validation of the major life changing decision profile (MLCDP)

Zaheer Bhatti — 2013-05-08T00:00:00Z

Background: Chronic diseases may influence patients taking major life changing decisions (MLCDs) concerning for example education, career, relationships, having children and retirement. A validated measure is needed to evaluate the impact of chronic diseases on MLCDs, improving assessment of their life-long burden. The aims of this study were to develop a validated questionnaire, the "Major Life Changing Decision Profile" (MLCDP) and to evaluate its psychometric properties. Methods: 50 interviews and two focus group meetings with dermatology patients and 258 questionnaires, completed by cardiology, rheumatology, nephrology, diabetes and respiratory disorder patients, were analysed for qualitative data using Nvivo8 software. Content validation was carried out by a panel of experts. The first version of the MLCDP was completed by 210 patients and an iterative process of multiple Exploratory Factor Analyses and item prevalence was used to guide item reduction. Face validity and practicability was assessed by patients. Results: 48 MLCDs were selected from analysis of the transcripts and questionnaires for the first version of the MLCDP, and reduced to 45 by combination of similar themes. There was a high intraclass correlation coefficient (0.7) between the 13 members of the content validation panel. Four more items were deleted leaving a 41-item MLCDP that was completed by 210 patients. The most frequently recorded MLCDs were decisions to change eating habits (71.4%), to change smoking/drinking alcohol habits (58.5%) and not to travel or go for holidays abroad (50.9%).Factor analysis suggested item number reduction from 41 to 34, to 29, then 23 items. However after taking into account item prevalence data as well as factor analysis results, 32 items were retained. The 32-item MLCDP has five domains education (3 items), job/career (9), family/relationships (5), social (10) and physical (5). The MLCDP score is expressed as the absolute number of decisions that have been affected. Conclusions: The 32-item (5 domains) MLCDP has been developed as an easy to complete generic tool for use in clinical practice and for quality of life and epidemiological research. Further validation is required.

Performance of the Dutch SF-36 version 2 as a measure of health-related quality of life in patients with rheumatoid arthritis

Peter ten Klooster — 2013-05-08T00:00:00Z

Background: The aim of this study was to examine the measurement properties of the Dutch SF-36 version 2 (SF-36v2) health survey in patients with rheumatoid arthritis (RA). Methods: Scaling assumptions, internal reliability, and internal construct validity were examined using available data from 1884 RA patients included in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. External construct validity and responsiveness to change were examined using baseline and 6-month follow-up data from a subset of 387 early RA patients participating in the DREAM remission induction cohort. Results: The individual items of the SF-36v2 adequately met scaling assumptions, although four items correlated too highly with items from different scales. Internal consistency was high for all eight scales and the physical and mental health components underlying the scales were replicated, supporting the use of the standard scoring algorithms. The SF-36v2 scales demonstrated minimal floor effects and ceiling effects were noteworthy only for the role-physical, social functioning, and role-emotional scales. Correlations with other core measures were as expected and the SF-36v2 showed excellent known-groups validity in distinguishing between patients with low or moderate-high disease activity. All scales related to physical health showed moderate to large responsiveness to change in patients that achieved low disease activity at six months. Conclusion: The SF-36v2 appears to be a psychometrically sound tool for the assessment of health-related quality of life of Dutch patients with RA.

Assessing the quality of life of health-referred children and adolescents with short stature: development and psychometric testing of the QoLISSY instrument

Monika Bullinger — 2013-05-07T00:00:00Z

Background: When evaluating the outcomes of treatment in paediatric endocrinology, the health-related quality of life (HrQoL) of the child is to be taken into consideration. Since few self--reported HrQoL instruments exist for children with diagnosed short stature (dSS), the objective of this study was to develop and psychometrically test a targeted HrQoL instrument for use in multinational clinical research. Methods: The target population were short stature (height < -2 SDS) children and adolescents (age 8--12 and 13--18 years) with a diagnosis of growth hormone deficiency (GHD) or idiopathic short stature (ISS), differing in growth hormone treatment status. Focus group discussions for concept and item generation, piloting of the questionnaire with cognitive debriefing, and instrument field testing with a retest were conducted simultaneously in five countries. After qualitative and preliminary quantitative analyses, psychometric testing of field test data in terms of reliability and validity including, confirmatory factor analyses (CFA) was performed. Results: Following item generation from focus group discussions, 124 items were included in a pilot test with a cognitive debriefing exercise providing preliminary feedback on item and domain operating characteristics. A field test with 268 participants showed high internal consistency reliabilities (alpha 0.82 -- 0.95), good correlations with generic measures (up to r = .58), significant known group differences (e.g. in height: F = 32, df 244, p < 0.001) and an acceptable CFA model fit suggesting construct validity of the three-domain core structure with 22 items, supplemented by three mediator domains with 29 items. Conclusions: The QoLISSY questionnaire is a promising step forward in assessing the impact of dSS on HrQoL. It is based on items generated from the subjective experience of short stature children referred for endocrine investigation, is validated for use in five languages and it is easy to administer in clinical and research settings.

Comparing children¿s self-report instruments for health-related quality of life using the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY)

Christina Petersson — 2013-05-04T00:00:00Z

Children with chronic conditions often experience a long treatment which can be complex and negatively impacts the child's well-being. In planning treatment and interventions for children with chronic conditions, it is important to measure health-related quality of life (HrQoL). HrQoL instruments are considered to be a patient-reported outcome measure (PROM) and should be used in routine practice. Purpose: The aim of this study was to compare the content dimensions of HrQoL instruments for children's self-reports using the framework of ICF-CY. Method: The sample consist of six instruments for health-related quality of life for children 5 to 18 years of age, which was used in the Swedish national quality registries for children and adolescents with chronic conditions. The following instruments were included: CHQ-CF, DCGM-37, EQ-5D-Y, KIDSCREEN-52, Kid-KINDL and PedsQL 4.0. The framework of the ICF-CY was used as the basis for the comparison. Results: There were 290 meaningful concepts identified and linked to 88 categories in the classification ICF-CY with 29 categories of the component body functions, 48 categories of the component activities and participation and 11 categories of the component environmental factors. No concept were linked to the component body structures. The comparison revealed that the items in the HrQoL instruments corresponded primarily with the domains of activities and less with environmental factors. Conclusions: In conclusion, the results confirm that ICF-CY provide a good framework for content comparisons that evaluate similarities and differences to ICF-CY categories. The results of this study revealed the need for greater consensus of content across different HrQoL instruments. To obtain a detailed description of children's HrQoL, DCGM-37 and KIDSCREEN-52 may be appropriate instruments to use that can increase the understanding of young patients’ needs.

Effects of a rapid response system on quality of life: a prospective cohort study in surgical patients before and after implementing a rapid response system

Friede Simmes — 2013-05-01T00:00:00Z

Background: The aim of a rapid response system (RRS) is to improve the timely recognition and treatment of ward patients with deteriorating vital signs The system is based on a set of clinical criteria that are used to assess patient’s vital signs on a general ward. Once a patient is evaluated as critical, a medical emergency team is activated to more thoroughly assess the patient’s physical condition and to initiate treatment. The medical emergency team included a critical care physician and a critical care nurse.AimTo assess the effect of an RRS on health-related quality of life (HRQOL). Methods: Prospective cohort study in surgical patients before and after implementing an RRS. HRQOL was measured using the EuroQol-5 dimensions (EQ-5D) and the EQ visual analogue scale (VAS) at pre surgery and at 3 and 6 months following surgery. Results: No statistical significant effects of RRS implementation on the EQ-5D index and EQ-VAS were found. This was also true for the subpopulation of patients with an unplanned intensive care unit admission. Regarding the EQ-5D dimensions, deterioration in the ‘mobility’ and ‘usual activities’ dimensions in the post-implementation group was significantly less compared to the pre-implementation group with a respective mean difference of 0.08 (p = 0.03) and 0.09 (p = 0.04) on a three-point scale at 6 months. Lower pre-surgery EQ-5D index and higher American Society of Anesthesiologists physical status (ASA-PS) scores were significantly associated with lower EQ-5D index scores at 3 and 6 months following surgery. Conclusions: Implementation of an RRS did not convincingly affect HRQOL following major surgery. We question if HRQOL is an adequate measure to assess the influence of an RRS. Pre-surgery HRQOL- and ASA-PS scores were strongly associated with HRQOL outcomes and may have abated the influence of the RRS implementation.