Joseph Cappelleri - Academia.edu (original) (raw)

Papers by Joseph Cappelleri

Health and quality of life outcomes, Jan 18, 2018

Health state (HS) utility values for patients with acute myeloid leukemia (AML), a hematological ... more Health state (HS) utility values for patients with acute myeloid leukemia (AML), a hematological malignancy, are not available in the United Kingdom (UK). This study aims to develop clinically sound HSs for previously untreated patients with AML and to assign utility values based on preferences of the general UK population. This study was conducted in the UK and comprised 2 stages. During the first stage, AML HSs were drafted based on evidence from a literature review of AML clinical and health-related quality-of-life studies (published January 2000-June 2016) and patient-reported outcome measures previously used in this population. A panel of UK hematologists with AML experience validated the clinical relevance and accuracy of the HSs. During the second stage, validated HSs were valued in an elicitation survey with a representative UK population sample using the time trade-off (TTO) method. Descriptive statistics and bivariate tests were obtained and performed. A total of eight HSs...

BMC musculoskeletal disorders, Aug 18, 2016

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint... more Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint structural deterioration. Driven by recent expectations that patients in clinical trials randomized to placebo should be 'rescued' with active therapy within 6 months of starting treatment, the relative benefit of arresting joint damage with biologic agents beyond this period is unclear. With longer-term evidence of the rate of joint deterioration with minimal treatment, the efficacy of biologic agents and novel treatments might be projected beyond the placebo-controlled phase observed in clinical trials. The aim of this study was to estimate radiographic structural deterioration over time in patients with moderate-to-severe RA minimally treated with DMARDs. A literature review identified evidence of joint structural deterioration in patients with (DMARD-IR population) and without (non-DMARD-IR population) a history of inadequate response to DMARDs. Patients were minimally treat...

American health & drug benefits, 2016

Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (R... more Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA), provides patients with an alternative to subcutaneously or intravenously administered biologic disease-modifying antirheumatic drugs (DMARDs). Little is known about patient preference for novel RA treatments. To investigate patient preferences for attributes associated with RA treatments. A choice-based conjoint survey was mailed to 1400 randomly selected commercially insured patients (aged 21-80 years) diagnosed with RA, who were continuously enrolled from May 1, 2012, through April 30, 2013, and had ≥2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 714.0 and no previous biologic DMARD use. Treatment attributes included route of administration; monthly out-of-pocket cost; frequency of administration; ability to reduce daily joint pain and swelling; likelihood of serious adverse events; improvement in the ability to p...

American health & drug benefits, 2012

Patient-reported outcomes (PROs) can play an important role in personalized medicine. PROs can be... more Patient-reported outcomes (PROs) can play an important role in personalized medicine. PROs can be viewed as an important fundamental tool to measure the extent of disease and the effect of treatment at the individual level, because they reflect the self-reported health state of the patient directly. However, their effective integration in personalized medicine requires addressing certain conceptual and methodological challenges, including instrument development and analytical issues. To evaluate methodological issues, such as multiple comparisons, missing data, and modeling approaches, associated with the analysis of data related to PRO and personalized medicine to further our understanding on the role of PRO data in personalized medicine. There is a growing recognition of the role of PROs in medical research, but their potential use in customizing healthcare is not widely appreciated. Emerging insights into the genetic basis of PROs could potentially lead to new pathways that may i...

Current Medical Research and Opinion, 2010

With a growing number of studies and comparators in MRSA skin infections, a unified framework for... more With a growing number of studies and comparators in MRSA skin infections, a unified framework for comparing treatments is needed for health technology assessment (HTA). The objective was to systematically assess the success rates of common antimicrobial agents for the treatment of complicated skin and soft tissue infections (cSSTIs) caused by MRSA. MEDLINE, EMBASE, and Cochrane databases were searched to identify published clinical trials in which dalbavancin, daptomycin, linezolid, telavancin, teicoplanin, tigecycline, and vancomycin were used to treat cSSTIs. Pooled efficacy estimates were generated from clinical and microbiological determinations of success for the MRSA-subgroups in cSSTI clinical trials using a Bayesian meta-analytic approach. Success rates for each antibiotic were reported with 95% Bayesian confidence intervals (called credible intervals [CrI]). In sensitivity analyses the impact of different model parameters and article quality were investigated. Out of 36 identified studies, 14 studies on six antibiotics with 28 treatment arms (n = 1840) were included in the analysis. No MRSA data in cSSTI were found for teicoplanin. The pooled success rate and CrI(95%) for each agent was: vancomycin (74.7%; CrI(95%): 64.1%-83.5%), dalbavancin (87.7%; CrI(95%): 74.6%-95.4%), linezolid (84.4%; CrI(95%): 76.6%-90.6%), telavancin (83.5%; CrI(95%): 73.6%-90.8%), daptomycin (78.1%; CrI(95%): 54.6%-93.2%) and tigecycline (70.4%; CrI(95%): 48.0%-87.6%). Comparisons between antibiotics suggested differences versus vancomycin for linezolid (+9.7%; CrI(95%): 4.4%-15.8%), dalbavancin (+13.1%; CrI(95%): 1.0%-23.8%), and telavancin (+8.8%; CrI(95%): 1.5-16.7%). The finding of lower vancomycin efficacy in MRSA cSSTI did not change in sensitivity analyses. The results of this meta-analysis suggest higher success rates for linezolid and the new glycopeptides (dalbavancin and telavancin) in MRSA-confirmed cSSTIs. The uncertainty margins reflect the study limitations including number of cases and indirect nature of the comparisons. This example of Bayesian meta-analysis for MRSA cSSTI provides a potential framework for comparisons that is useful for HTA and formulary decision-making.

Appendix 1: The FACIT-Fatigue scale. (DOCX 255 kb)

Appendix 1. Work Productivity and Activity Impairment Questionnaire (WPAI). Appendix 2. Terms and... more Appendix 1. Work Productivity and Activity Impairment Questionnaire (WPAI). Appendix 2. Terms and Strings Used in Electronic Database Literature Searches. (DOCX 21 kb)

Value in Health, 2018

Background: The Functional Assessment of Cancer Therapy eKidney Symptom Index Disease-Related Sym... more Background: The Functional Assessment of Cancer Therapy eKidney Symptom Index Disease-Related Symptoms (FKSI-DRS) is important to gauge clinical benefit in metastatic renal cell carcinoma (mRCC). Objectives: To estimate important difference (ID) in FKSI-DRS scores that is considered to be meaningful when comparing treatment effect between groups, using mRCC trial data. Methods: Data were derived from two pivotal phase III mRCC trials comparing sunitinib versus interferon alfa (N ¼ 750) in first-line mRCC, and axitinib versus sorafenib (N ¼ 723) in second-line mRCC. The change from baseline in FKSI-DRS score was examined as a function of a set of anchors using the repeated-measures model. Several anchors were evaluated: FKSI item "I am bothered by side effects of treatment," EuroQol five-dimensional questionnaire utility score, and adverse events. Results: When the "I am bothered by side effects of treatment" score was used as an anchor, the ID ranged between 1.2 and 1.3 points. When change in the EuroQol fivedimensional questionnaire utility score was used as an anchor, the FKSI-DRS ID ranged between 0.62 and 0.63 points. Selecting the adverse events that corresponded to a maximum worsening in the FKSI-DRS score in either trial, the ID ranged between 0.62 and 0.74 points. Conclusions: Among patients undergoing treatment for mRCC, between-group differences in FKSI-DRS scores as low as 1 point might be meaningful.

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Jun 1, 2018

The US Food and Drug Administration and the Critical Path Institute's Patient-Reported Outcom... more The US Food and Drug Administration and the Critical Path Institute's Patient-Reported Outcome (PRO) Consortium convened a cosponsored workshop on the use of PRO measures to inform the assessment of safety and tolerability in cancer clinical trials. A broad array of international stakeholders involved in oncology drug development and PRO measurement science provided perspectives on the role of PRO measures to provide complementary clinical data on the symptomatic side effects of anticancer agents. Speakers and panelists explored the utility of information derived from existing and emerging PRO measures, focusing on the PRO version of the National Cancer Institute's Common Terminology Criteria for Adverse Events. Panelists and speakers discussed potential ways to improve the collection, analysis, and presentation of PRO data describing symptomatic adverse events to support drug development and better inform regulatory and treatment decisions. Workshop participants concluded t...

Journal of Crohn's & colitis, Jan 27, 2018

This review is the first to evaluate the burden of ulcerative colitis [UC] on patients' quali... more This review is the first to evaluate the burden of ulcerative colitis [UC] on patients' quality of life by synthesizing data from studies comparing scores from the SF-36® Health Survey, a generic measure assessing eight quality-of-life domains, between UC patients and matched reference samples. A systematic review of the published literature identified articles reporting SF-36 domains or physical and mental component summary scores [PCS, MCS] from UC and reference samples. Burden of disease for each SF-36 domain was then summarized across studies by comparing weighted mean differences in scores between patient and reference samples with minimally important difference thresholds. Thirty articles met pre-specified inclusion criteria. SF-36 scores were extracted from five samples of patients with active disease, 11 samples with a mixture of disease activity, five samples of patients in clinical remission, and 13 samples of patients following proctocolectomy with ileostomy or ileal ...

Pain practice : the official journal of World Institute of Pain, Jan 18, 2017

To compare fibromyalgia (FM) characteristics among patients identified in a community-based chron... more To compare fibromyalgia (FM) characteristics among patients identified in a community-based chronic pain cohort based on traditional International Classification of Diagnoses 9th revision (ICD-9) diagnostic coding, with that of patients identified using a novel predictive model. This retrospective study used data collected from July 1999 to February 17, 2015, in multiple chronic pain clinics in the United States. Patients were assigned to the FM case group based on specific inclusion criteria using ICD-9 codes or, separately, from results of a novel FM predictive model that was developed using random forest and logistic regression techniques. Propensity scoring (1:1) matched FM patients (cases) to nonmalignant chronic pain patients without FM (controls). Patient-reported measures (eg, pain, fatigue, quality of sleep) and clinical characteristics (ie, comorbidities, procedures, and regions of pain) were outcomes for analysis. Nine ICD-9 clinical modification diagnoses had odds ratios...

Current medical research and opinion, 2017

Collecting data that helps evaluate different types of pain may improve physicians' decision-... more Collecting data that helps evaluate different types of pain may improve physicians' decision-making with regard to treatment selection and on-going monitoring of patients. To date, no chronic pain assessments have been widely implemented in primary care. The aim of this study was to psychometrically validate the electronic Chronic Pain Questions (eCPQ) in a primary care setting. All men and women ≥18 years arriving at two similar primary care clinics in southeastern Michigan were invited to participate. Clinic staff verbally administered the eCPQ to patients and recorded their answers into the electronic medical record (EMR) prior to physician consultation with results available for physician review. Concurrent validity was assessed using Spearman correlations between eCPQ and patient-completed ancillary measures. Known-group validity was assessed by stratifying patients on self-reported chronic pain as well as by pain diagnosis (i.e. ICD-9 codes). To compare patients with chron...

Postgraduate medicine, 2017

The Chronic Pain Questions (CPQ) were developed for clinical use with the aim of supporting prima... more The Chronic Pain Questions (CPQ) were developed for clinical use with the aim of supporting primary care physicians in the screening, assessment and monitoring of patients with chronic pain. the purpose of this study was to examine the ability of the cpq CPQ to discriminate between patients with neuropathic pain (nep) versus those with sensory hypersensitivity (sh). Adult men and women with a diagnosis of a NeP or SH condition were recruited from 5 clinical sites across the United States. Participants completed a series of self-administered questionnaires, including the CPQ. Continuous variables were compared between groups with independent t-tests; categorical variables were compared with chi-square analyses. A series of exploratory logistic regressions were performed to discern optimal screening criteria for SH using CPQ responses. 98 participants, 68 with physician-confirmed diagnoses of SH and 30 with NeP, participated. 81.6% were female, 73.5% Caucasian, and mean (± SD) age was...

The journal of sexual medicine, 2017

First, there are several types of item response theory models. 2,3 In our article, we considered ... more First, there are several types of item response theory models. 2,3 In our article, we considered one type: a Rasch model with binary item responses.

BMC neurology, Jan 4, 2017

painDETECT (PD-Q) is a self-reported assessment of pain qualities developed as a screening tool f... more painDETECT (PD-Q) is a self-reported assessment of pain qualities developed as a screening tool for pain of neuropathic origin. Rasch analysis is a strategy for examining the measurement characteristics of a scale using a form of item response theory. We conducted a Rasch analysis to consider if the scoring and measurement properties of PD-Q would support its use as an outcome measure. Rasch analysis was conducted on PD-Q scores drawn from a cross-sectional study of the burden and costs of NeP. The analysis followed an iterative process based on recommendations in the literature, including examination of sequential scoring categories, unidimensionality, reliability and differential item function. Data from 624 persons with a diagnosis of painful diabetic polyneuropathy, small fibre neuropathy, and neuropathic pain associated with chronic low back pain, spinal cord injury, HIV-related pain, or chronic post-surgical pain was used for this analysis. PD-Q demonstrated fit to the Rasch m...

The open rheumatology journal, 2016

Longitudinal research on outcomes of patients with fibromyalgia is limited. To assess clinician a... more Longitudinal research on outcomes of patients with fibromyalgia is limited. To assess clinician and patient-reported outcomes over time among fibromyalgia patients. At enrollment (Baseline) and follow-up (approximately 2 years later), consented patients were screened for chronic widespread pain (CWP), attended a physician site visit to determine fibromyalgia status, and completed an online questionnaire assessing pain, sleep, function, health status, productivity, medications, and healthcare resource use. Seventy-six fibromyalgia patients participated at both time points (at Baseline: 86.8% white, 89.5% female, mean age 50.9 years, and mean duration of fibromyalgia 4.1 years). Mean number of tender points at each physician visit was 14.1 and 13.5, respectively; 11 patients no longer screened positive for CWP at follow-up. A majority reported medication use for pain (59.2% at Baseline, 62.0% at Follow-up). The most common medication classes were opioids (32.4%), SSRIs (16.9%), and tr...

Journal of pain research, 2017

To develop a claims-based algorithm for identifying patients who are adherent versus nonadherent ... more To develop a claims-based algorithm for identifying patients who are adherent versus nonadherent to published guidelines for chronic pain management. Using medical and pharmacy health care claims from the MarketScan® Commercial and Medicare Supplemental Databases, patients were selected during July 1, 2010, to June 30, 2012, with the following chronic pain conditions: osteoarthritis (OA), gout (GT), painful diabetic peripheral neuropathy (pDPN), post-herpetic neuralgia (PHN), and fibromyalgia (FM). Patients newly diagnosed with 12 months of continuous medical and pharmacy benefits both before and after initial diagnosis (index date) were categorized as adherent, nonadherent, or unsure according to the guidelines-based algorithm using disease-specific pain medication classes grouped as first-line, later-line, or not recommended. Descriptive and multivariate analyses compared patient outcomes with algorithm-derived categorization endpoints. A total of 441,465 OA patients, 76,361 GT pa...

ClinicoEconomics and Outcomes Research, 2016

The management of fibromyalgia (FM), a chronic musculoskeletal disease, remains challenging, and ... more The management of fibromyalgia (FM), a chronic musculoskeletal disease, remains challenging, and patients with FM are often characterized by high health care resource utilization. This study sought to explore potential drivers of all-cause health care resource utilization and other factors associated with high resource use, using a large electronic health records (EHR) database to explore data from patients diagnosed with FM. Methods: This was a retrospective analysis of de-identified EHR data from the Humedica database. Adults (≥18 years) with FM were identified based on ≥2 International Classification of Diseases, Ninth Revision codes for FM (729.1) ≥30 days apart between January 1, 2008 and December 31, 2012 and were required to have evidence of ≥12 months continuous care pre-and post-index; first FM diagnosis was the index event; 12-month pre-and post-index reporting periods. Multivariable analysis evaluated relationships between variables and resource utilization. Results: Patients were predominantly female (81.4%), Caucasian (87.7%), with a mean (standard deviation) age of 54.4 (14.8) years. The highest health care resource utilization was observed for the categories of "medication orders" and "physician office visits," with 12-month post-index means of 21.2 (21.5) drug orders/patient and 15.1 (18.1) office visits/patient; the latter accounted for 73.3% of all health care visits. Opioids were the most common prescription medication, 44.3% of all patients. The chance of high resource use was significantly increased (P<0.001) 26% among African-Americans vs Caucasians and for patients with specific comorbid conditions ranging from 6% (musculoskeletal pain or depression/bipolar disorder) to 21% (congestive heart failure). Factors significantly associated with increased medications ordered included being female (P<0.001) and specific comorbid conditions (P<0.05). Conclusion: Physician office visits and pharmacotherapy orders were key drivers of all-cause health care utilization, with demographic factors, opioid use, and specific comorbidities associated with resource intensity. Health systems and providers may find their EHRs to be a useful tool for identifying and managing resource-intensive FM patients.

ClinicoEconomics and Outcomes Research, 2016

Background: painDETECT is a screening measure for neuropathic pain. The nine-item version consist... more Background: painDETECT is a screening measure for neuropathic pain. The nine-item version consists of seven sensory items (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure), a pain course pattern item, and a pain radiation item. The seven-item version consists only of the sensory items. Total scores of both versions discriminate average pain-severity levels (mild, moderate, and severe), but their ability to discriminate individual item severity has not been evaluated. Methods: Data were from a cross-sectional, observational study of six neuropathic pain conditions (N=624). Average pain severity was evaluated using the Brief Pain Inventory-Short Form, with severity levels defined using established cut points for distinguishing mild, moderate, and severe pain. The Wilcoxon rank sum test was followed by ridit analysis to represent the probability that a randomly selected subject from one average pain-severity level had a more favorable outcome on the specific painDETECT item relative to a randomly selected subject from a comparator severity level. Results: A probability >50% for a better outcome (less severe pain) was significantly observed for each pain symptom item. The lowest probability was 56.3% (on numbness for mild vs moderate pain) and highest probability was 76.4% (on cold/heat for mild vs severe pain). The pain radiation item was significant (P<0.05) and consistent with pain symptoms, as well as with total scores for both painDETECT versions; only the pain course item did not differ. Conclusion: painDETECT differentiates severity such that the ability to discriminate average pain also distinguishes individual pain item severity in an interpretable manner. Pain-severity levels can serve as proxies to determine treatment effects, thus indicating probabilities for more favorable outcomes on pain symptoms.

Patient Related Outcome Measures, 2016

To psychometrically evaluate painDETECT, a patient-reported screening questionnaire for neuropath... more To psychometrically evaluate painDETECT, a patient-reported screening questionnaire for neuropathic pain (NeP), for discriminating among sensory pain symptoms (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure). Methods: The seven-item version of painDETECT provides an overall score that targets only sensory symptoms, while the nine-item version adds responses on two items to the overall score, covering pain course pattern and pain radiation. Both versions have relevance in terms of characterizing broad NeP. The nine-and seven-item versions of painDETECT were administered to subjects with confirmed NeP across six conditions identified during office visits to US community-based physicians. Responses on the sensory symptom items were dichotomized into "at least moderate" (ie, moderate, strongly, very strongly) relative to the combined other responses (never, hardly noticed, slightly). Logistic regression of dichotomized variables on the total painDETECT score provided probabilities of experiencing each symptom across the range of painDETECT scores. Results: Both painDETECT versions discriminated among the symptoms with similar probabilities across the score ranges. Using these data, the probability of moderately experiencing each pain sensory item was estimated for a particular score, providing a pain profile. Additionally, the likelihood of experiencing each sensation was determined for a discrete increase in score, ie, the odds of at least a moderate sensation of burning (versus less than a moderate sensation) was 1.29 for a 1-point increase, 3.52 for a 5-point increase, and 12.42 for every 10-point increase in the nine-item painDETECT score. Conclusion: painDETECT differentiates pain profiles across the range of scores such that, for a particular score, the probability of experiencing at least a moderate sensation of each symptom was determined and compared. These results can help characterize NeP symptomatology, enrich interpretation of painDETECT scores, and provide a basis for individualizing NeP management.

Health and quality of life outcomes, Jan 18, 2018

Health state (HS) utility values for patients with acute myeloid leukemia (AML), a hematological ... more Health state (HS) utility values for patients with acute myeloid leukemia (AML), a hematological malignancy, are not available in the United Kingdom (UK). This study aims to develop clinically sound HSs for previously untreated patients with AML and to assign utility values based on preferences of the general UK population. This study was conducted in the UK and comprised 2 stages. During the first stage, AML HSs were drafted based on evidence from a literature review of AML clinical and health-related quality-of-life studies (published January 2000-June 2016) and patient-reported outcome measures previously used in this population. A panel of UK hematologists with AML experience validated the clinical relevance and accuracy of the HSs. During the second stage, validated HSs were valued in an elicitation survey with a representative UK population sample using the time trade-off (TTO) method. Descriptive statistics and bivariate tests were obtained and performed. A total of eight HSs...

BMC musculoskeletal disorders, Aug 18, 2016

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint... more Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint structural deterioration. Driven by recent expectations that patients in clinical trials randomized to placebo should be 'rescued' with active therapy within 6 months of starting treatment, the relative benefit of arresting joint damage with biologic agents beyond this period is unclear. With longer-term evidence of the rate of joint deterioration with minimal treatment, the efficacy of biologic agents and novel treatments might be projected beyond the placebo-controlled phase observed in clinical trials. The aim of this study was to estimate radiographic structural deterioration over time in patients with moderate-to-severe RA minimally treated with DMARDs. A literature review identified evidence of joint structural deterioration in patients with (DMARD-IR population) and without (non-DMARD-IR population) a history of inadequate response to DMARDs. Patients were minimally treat...

American health & drug benefits, 2016

Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (R... more Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA), provides patients with an alternative to subcutaneously or intravenously administered biologic disease-modifying antirheumatic drugs (DMARDs). Little is known about patient preference for novel RA treatments. To investigate patient preferences for attributes associated with RA treatments. A choice-based conjoint survey was mailed to 1400 randomly selected commercially insured patients (aged 21-80 years) diagnosed with RA, who were continuously enrolled from May 1, 2012, through April 30, 2013, and had ≥2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 714.0 and no previous biologic DMARD use. Treatment attributes included route of administration; monthly out-of-pocket cost; frequency of administration; ability to reduce daily joint pain and swelling; likelihood of serious adverse events; improvement in the ability to p...

American health & drug benefits, 2012

Patient-reported outcomes (PROs) can play an important role in personalized medicine. PROs can be... more Patient-reported outcomes (PROs) can play an important role in personalized medicine. PROs can be viewed as an important fundamental tool to measure the extent of disease and the effect of treatment at the individual level, because they reflect the self-reported health state of the patient directly. However, their effective integration in personalized medicine requires addressing certain conceptual and methodological challenges, including instrument development and analytical issues. To evaluate methodological issues, such as multiple comparisons, missing data, and modeling approaches, associated with the analysis of data related to PRO and personalized medicine to further our understanding on the role of PRO data in personalized medicine. There is a growing recognition of the role of PROs in medical research, but their potential use in customizing healthcare is not widely appreciated. Emerging insights into the genetic basis of PROs could potentially lead to new pathways that may i...

Current Medical Research and Opinion, 2010

With a growing number of studies and comparators in MRSA skin infections, a unified framework for... more With a growing number of studies and comparators in MRSA skin infections, a unified framework for comparing treatments is needed for health technology assessment (HTA). The objective was to systematically assess the success rates of common antimicrobial agents for the treatment of complicated skin and soft tissue infections (cSSTIs) caused by MRSA. MEDLINE, EMBASE, and Cochrane databases were searched to identify published clinical trials in which dalbavancin, daptomycin, linezolid, telavancin, teicoplanin, tigecycline, and vancomycin were used to treat cSSTIs. Pooled efficacy estimates were generated from clinical and microbiological determinations of success for the MRSA-subgroups in cSSTI clinical trials using a Bayesian meta-analytic approach. Success rates for each antibiotic were reported with 95% Bayesian confidence intervals (called credible intervals [CrI]). In sensitivity analyses the impact of different model parameters and article quality were investigated. Out of 36 identified studies, 14 studies on six antibiotics with 28 treatment arms (n = 1840) were included in the analysis. No MRSA data in cSSTI were found for teicoplanin. The pooled success rate and CrI(95%) for each agent was: vancomycin (74.7%; CrI(95%): 64.1%-83.5%), dalbavancin (87.7%; CrI(95%): 74.6%-95.4%), linezolid (84.4%; CrI(95%): 76.6%-90.6%), telavancin (83.5%; CrI(95%): 73.6%-90.8%), daptomycin (78.1%; CrI(95%): 54.6%-93.2%) and tigecycline (70.4%; CrI(95%): 48.0%-87.6%). Comparisons between antibiotics suggested differences versus vancomycin for linezolid (+9.7%; CrI(95%): 4.4%-15.8%), dalbavancin (+13.1%; CrI(95%): 1.0%-23.8%), and telavancin (+8.8%; CrI(95%): 1.5-16.7%). The finding of lower vancomycin efficacy in MRSA cSSTI did not change in sensitivity analyses. The results of this meta-analysis suggest higher success rates for linezolid and the new glycopeptides (dalbavancin and telavancin) in MRSA-confirmed cSSTIs. The uncertainty margins reflect the study limitations including number of cases and indirect nature of the comparisons. This example of Bayesian meta-analysis for MRSA cSSTI provides a potential framework for comparisons that is useful for HTA and formulary decision-making.

Appendix 1: The FACIT-Fatigue scale. (DOCX 255 kb)

Appendix 1. Work Productivity and Activity Impairment Questionnaire (WPAI). Appendix 2. Terms and... more Appendix 1. Work Productivity and Activity Impairment Questionnaire (WPAI). Appendix 2. Terms and Strings Used in Electronic Database Literature Searches. (DOCX 21 kb)

Value in Health, 2018

Background: The Functional Assessment of Cancer Therapy eKidney Symptom Index Disease-Related Sym... more Background: The Functional Assessment of Cancer Therapy eKidney Symptom Index Disease-Related Symptoms (FKSI-DRS) is important to gauge clinical benefit in metastatic renal cell carcinoma (mRCC). Objectives: To estimate important difference (ID) in FKSI-DRS scores that is considered to be meaningful when comparing treatment effect between groups, using mRCC trial data. Methods: Data were derived from two pivotal phase III mRCC trials comparing sunitinib versus interferon alfa (N ¼ 750) in first-line mRCC, and axitinib versus sorafenib (N ¼ 723) in second-line mRCC. The change from baseline in FKSI-DRS score was examined as a function of a set of anchors using the repeated-measures model. Several anchors were evaluated: FKSI item "I am bothered by side effects of treatment," EuroQol five-dimensional questionnaire utility score, and adverse events. Results: When the "I am bothered by side effects of treatment" score was used as an anchor, the ID ranged between 1.2 and 1.3 points. When change in the EuroQol fivedimensional questionnaire utility score was used as an anchor, the FKSI-DRS ID ranged between 0.62 and 0.63 points. Selecting the adverse events that corresponded to a maximum worsening in the FKSI-DRS score in either trial, the ID ranged between 0.62 and 0.74 points. Conclusions: Among patients undergoing treatment for mRCC, between-group differences in FKSI-DRS scores as low as 1 point might be meaningful.

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, Jun 1, 2018

The US Food and Drug Administration and the Critical Path Institute's Patient-Reported Outcom... more The US Food and Drug Administration and the Critical Path Institute's Patient-Reported Outcome (PRO) Consortium convened a cosponsored workshop on the use of PRO measures to inform the assessment of safety and tolerability in cancer clinical trials. A broad array of international stakeholders involved in oncology drug development and PRO measurement science provided perspectives on the role of PRO measures to provide complementary clinical data on the symptomatic side effects of anticancer agents. Speakers and panelists explored the utility of information derived from existing and emerging PRO measures, focusing on the PRO version of the National Cancer Institute's Common Terminology Criteria for Adverse Events. Panelists and speakers discussed potential ways to improve the collection, analysis, and presentation of PRO data describing symptomatic adverse events to support drug development and better inform regulatory and treatment decisions. Workshop participants concluded t...

Journal of Crohn's & colitis, Jan 27, 2018

This review is the first to evaluate the burden of ulcerative colitis [UC] on patients' quali... more This review is the first to evaluate the burden of ulcerative colitis [UC] on patients' quality of life by synthesizing data from studies comparing scores from the SF-36® Health Survey, a generic measure assessing eight quality-of-life domains, between UC patients and matched reference samples. A systematic review of the published literature identified articles reporting SF-36 domains or physical and mental component summary scores [PCS, MCS] from UC and reference samples. Burden of disease for each SF-36 domain was then summarized across studies by comparing weighted mean differences in scores between patient and reference samples with minimally important difference thresholds. Thirty articles met pre-specified inclusion criteria. SF-36 scores were extracted from five samples of patients with active disease, 11 samples with a mixture of disease activity, five samples of patients in clinical remission, and 13 samples of patients following proctocolectomy with ileostomy or ileal ...

Pain practice : the official journal of World Institute of Pain, Jan 18, 2017

To compare fibromyalgia (FM) characteristics among patients identified in a community-based chron... more To compare fibromyalgia (FM) characteristics among patients identified in a community-based chronic pain cohort based on traditional International Classification of Diagnoses 9th revision (ICD-9) diagnostic coding, with that of patients identified using a novel predictive model. This retrospective study used data collected from July 1999 to February 17, 2015, in multiple chronic pain clinics in the United States. Patients were assigned to the FM case group based on specific inclusion criteria using ICD-9 codes or, separately, from results of a novel FM predictive model that was developed using random forest and logistic regression techniques. Propensity scoring (1:1) matched FM patients (cases) to nonmalignant chronic pain patients without FM (controls). Patient-reported measures (eg, pain, fatigue, quality of sleep) and clinical characteristics (ie, comorbidities, procedures, and regions of pain) were outcomes for analysis. Nine ICD-9 clinical modification diagnoses had odds ratios...

Current medical research and opinion, 2017

Collecting data that helps evaluate different types of pain may improve physicians' decision-... more Collecting data that helps evaluate different types of pain may improve physicians' decision-making with regard to treatment selection and on-going monitoring of patients. To date, no chronic pain assessments have been widely implemented in primary care. The aim of this study was to psychometrically validate the electronic Chronic Pain Questions (eCPQ) in a primary care setting. All men and women ≥18 years arriving at two similar primary care clinics in southeastern Michigan were invited to participate. Clinic staff verbally administered the eCPQ to patients and recorded their answers into the electronic medical record (EMR) prior to physician consultation with results available for physician review. Concurrent validity was assessed using Spearman correlations between eCPQ and patient-completed ancillary measures. Known-group validity was assessed by stratifying patients on self-reported chronic pain as well as by pain diagnosis (i.e. ICD-9 codes). To compare patients with chron...

Postgraduate medicine, 2017

The Chronic Pain Questions (CPQ) were developed for clinical use with the aim of supporting prima... more The Chronic Pain Questions (CPQ) were developed for clinical use with the aim of supporting primary care physicians in the screening, assessment and monitoring of patients with chronic pain. the purpose of this study was to examine the ability of the cpq CPQ to discriminate between patients with neuropathic pain (nep) versus those with sensory hypersensitivity (sh). Adult men and women with a diagnosis of a NeP or SH condition were recruited from 5 clinical sites across the United States. Participants completed a series of self-administered questionnaires, including the CPQ. Continuous variables were compared between groups with independent t-tests; categorical variables were compared with chi-square analyses. A series of exploratory logistic regressions were performed to discern optimal screening criteria for SH using CPQ responses. 98 participants, 68 with physician-confirmed diagnoses of SH and 30 with NeP, participated. 81.6% were female, 73.5% Caucasian, and mean (± SD) age was...

The journal of sexual medicine, 2017

First, there are several types of item response theory models. 2,3 In our article, we considered ... more First, there are several types of item response theory models. 2,3 In our article, we considered one type: a Rasch model with binary item responses.

BMC neurology, Jan 4, 2017

painDETECT (PD-Q) is a self-reported assessment of pain qualities developed as a screening tool f... more painDETECT (PD-Q) is a self-reported assessment of pain qualities developed as a screening tool for pain of neuropathic origin. Rasch analysis is a strategy for examining the measurement characteristics of a scale using a form of item response theory. We conducted a Rasch analysis to consider if the scoring and measurement properties of PD-Q would support its use as an outcome measure. Rasch analysis was conducted on PD-Q scores drawn from a cross-sectional study of the burden and costs of NeP. The analysis followed an iterative process based on recommendations in the literature, including examination of sequential scoring categories, unidimensionality, reliability and differential item function. Data from 624 persons with a diagnosis of painful diabetic polyneuropathy, small fibre neuropathy, and neuropathic pain associated with chronic low back pain, spinal cord injury, HIV-related pain, or chronic post-surgical pain was used for this analysis. PD-Q demonstrated fit to the Rasch m...

The open rheumatology journal, 2016

Longitudinal research on outcomes of patients with fibromyalgia is limited. To assess clinician a... more Longitudinal research on outcomes of patients with fibromyalgia is limited. To assess clinician and patient-reported outcomes over time among fibromyalgia patients. At enrollment (Baseline) and follow-up (approximately 2 years later), consented patients were screened for chronic widespread pain (CWP), attended a physician site visit to determine fibromyalgia status, and completed an online questionnaire assessing pain, sleep, function, health status, productivity, medications, and healthcare resource use. Seventy-six fibromyalgia patients participated at both time points (at Baseline: 86.8% white, 89.5% female, mean age 50.9 years, and mean duration of fibromyalgia 4.1 years). Mean number of tender points at each physician visit was 14.1 and 13.5, respectively; 11 patients no longer screened positive for CWP at follow-up. A majority reported medication use for pain (59.2% at Baseline, 62.0% at Follow-up). The most common medication classes were opioids (32.4%), SSRIs (16.9%), and tr...

Journal of pain research, 2017

To develop a claims-based algorithm for identifying patients who are adherent versus nonadherent ... more To develop a claims-based algorithm for identifying patients who are adherent versus nonadherent to published guidelines for chronic pain management. Using medical and pharmacy health care claims from the MarketScan® Commercial and Medicare Supplemental Databases, patients were selected during July 1, 2010, to June 30, 2012, with the following chronic pain conditions: osteoarthritis (OA), gout (GT), painful diabetic peripheral neuropathy (pDPN), post-herpetic neuralgia (PHN), and fibromyalgia (FM). Patients newly diagnosed with 12 months of continuous medical and pharmacy benefits both before and after initial diagnosis (index date) were categorized as adherent, nonadherent, or unsure according to the guidelines-based algorithm using disease-specific pain medication classes grouped as first-line, later-line, or not recommended. Descriptive and multivariate analyses compared patient outcomes with algorithm-derived categorization endpoints. A total of 441,465 OA patients, 76,361 GT pa...

ClinicoEconomics and Outcomes Research, 2016

The management of fibromyalgia (FM), a chronic musculoskeletal disease, remains challenging, and ... more The management of fibromyalgia (FM), a chronic musculoskeletal disease, remains challenging, and patients with FM are often characterized by high health care resource utilization. This study sought to explore potential drivers of all-cause health care resource utilization and other factors associated with high resource use, using a large electronic health records (EHR) database to explore data from patients diagnosed with FM. Methods: This was a retrospective analysis of de-identified EHR data from the Humedica database. Adults (≥18 years) with FM were identified based on ≥2 International Classification of Diseases, Ninth Revision codes for FM (729.1) ≥30 days apart between January 1, 2008 and December 31, 2012 and were required to have evidence of ≥12 months continuous care pre-and post-index; first FM diagnosis was the index event; 12-month pre-and post-index reporting periods. Multivariable analysis evaluated relationships between variables and resource utilization. Results: Patients were predominantly female (81.4%), Caucasian (87.7%), with a mean (standard deviation) age of 54.4 (14.8) years. The highest health care resource utilization was observed for the categories of "medication orders" and "physician office visits," with 12-month post-index means of 21.2 (21.5) drug orders/patient and 15.1 (18.1) office visits/patient; the latter accounted for 73.3% of all health care visits. Opioids were the most common prescription medication, 44.3% of all patients. The chance of high resource use was significantly increased (P<0.001) 26% among African-Americans vs Caucasians and for patients with specific comorbid conditions ranging from 6% (musculoskeletal pain or depression/bipolar disorder) to 21% (congestive heart failure). Factors significantly associated with increased medications ordered included being female (P<0.001) and specific comorbid conditions (P<0.05). Conclusion: Physician office visits and pharmacotherapy orders were key drivers of all-cause health care utilization, with demographic factors, opioid use, and specific comorbidities associated with resource intensity. Health systems and providers may find their EHRs to be a useful tool for identifying and managing resource-intensive FM patients.

ClinicoEconomics and Outcomes Research, 2016

Background: painDETECT is a screening measure for neuropathic pain. The nine-item version consist... more Background: painDETECT is a screening measure for neuropathic pain. The nine-item version consists of seven sensory items (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure), a pain course pattern item, and a pain radiation item. The seven-item version consists only of the sensory items. Total scores of both versions discriminate average pain-severity levels (mild, moderate, and severe), but their ability to discriminate individual item severity has not been evaluated. Methods: Data were from a cross-sectional, observational study of six neuropathic pain conditions (N=624). Average pain severity was evaluated using the Brief Pain Inventory-Short Form, with severity levels defined using established cut points for distinguishing mild, moderate, and severe pain. The Wilcoxon rank sum test was followed by ridit analysis to represent the probability that a randomly selected subject from one average pain-severity level had a more favorable outcome on the specific painDETECT item relative to a randomly selected subject from a comparator severity level. Results: A probability >50% for a better outcome (less severe pain) was significantly observed for each pain symptom item. The lowest probability was 56.3% (on numbness for mild vs moderate pain) and highest probability was 76.4% (on cold/heat for mild vs severe pain). The pain radiation item was significant (P<0.05) and consistent with pain symptoms, as well as with total scores for both painDETECT versions; only the pain course item did not differ. Conclusion: painDETECT differentiates severity such that the ability to discriminate average pain also distinguishes individual pain item severity in an interpretable manner. Pain-severity levels can serve as proxies to determine treatment effects, thus indicating probabilities for more favorable outcomes on pain symptoms.

Patient Related Outcome Measures, 2016

To psychometrically evaluate painDETECT, a patient-reported screening questionnaire for neuropath... more To psychometrically evaluate painDETECT, a patient-reported screening questionnaire for neuropathic pain (NeP), for discriminating among sensory pain symptoms (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure). Methods: The seven-item version of painDETECT provides an overall score that targets only sensory symptoms, while the nine-item version adds responses on two items to the overall score, covering pain course pattern and pain radiation. Both versions have relevance in terms of characterizing broad NeP. The nine-and seven-item versions of painDETECT were administered to subjects with confirmed NeP across six conditions identified during office visits to US community-based physicians. Responses on the sensory symptom items were dichotomized into "at least moderate" (ie, moderate, strongly, very strongly) relative to the combined other responses (never, hardly noticed, slightly). Logistic regression of dichotomized variables on the total painDETECT score provided probabilities of experiencing each symptom across the range of painDETECT scores. Results: Both painDETECT versions discriminated among the symptoms with similar probabilities across the score ranges. Using these data, the probability of moderately experiencing each pain sensory item was estimated for a particular score, providing a pain profile. Additionally, the likelihood of experiencing each sensation was determined for a discrete increase in score, ie, the odds of at least a moderate sensation of burning (versus less than a moderate sensation) was 1.29 for a 1-point increase, 3.52 for a 5-point increase, and 12.42 for every 10-point increase in the nine-item painDETECT score. Conclusion: painDETECT differentiates pain profiles across the range of scores such that, for a particular score, the probability of experiencing at least a moderate sensation of each symptom was determined and compared. These results can help characterize NeP symptomatology, enrich interpretation of painDETECT scores, and provide a basis for individualizing NeP management.