Real-world evidence in the reassessment of oncology therapies: payer perceptions from five countries.

Aim: This study explored the perceived value of real-world evidence (RWE) in the reassessment of oncology therapies by collecting the perspectives of health technology assessment/payer decision-makers. Materials & methods: A web-based survey was conducted using the Market Access Transformation Rapid Payer Response online portal. 30 participants from France, Germany, Spain, the UK and the USA were recruited based on their expertise. Results: Participants agreed that the most common uses of RWE are to confirm efficacy and safety results from randomized controlled trials and to reevaluate the projected utilization of an oncology therapy. We found variability in other reported uses of RWE. Conclusion: The organizations developing RWE should ensure that their plans recognize the heterogeneity in payer perceptions.

A survey from the Market Access Transformation RPR portal queried decision-makers from five countries about the value of real-world evidence in oncology therapy reassessment. Participants agreed that RWE can confirm efficacy/safety and reevaluate utilization, but other uses varied.

Developing Patient-Centered Real-World Evidence: Emerging Methods Recommendations From a Consensus Process.

OBJECTIVES: The Joint ISPOR-ISPE Special Task Force on Real-World Evidence included patient/stakeholder engagement as a recommended good procedural practice when designing, conducting, and disseminating real-world evidence (RWE). However, there are no guidelines describing how patient experience data (PED) can be applied when designing real-world data (RWD) studies. This article describes development of consensus recommendations to guide researchers in applying PED to develop patient-centered RWE. METHODS: A multidisciplinary advisory board, identified through recommendations of collaborators, was established to guide development of recommendations. Semistructured interviews were conducted to identify how experienced RWD researchers (n = 15) would apply PED when designing a hypothetical RWD study. Transcripts were analyzed and emerging themes developed into preliminary methods recommendations. An eDelphi survey (n = 26) was conducted to refine/develop consensus on the draft recommendations. RESULTS: We identified 13 recommendations for incorporating PED throughout the design, conduct, and translation of RWE. The recommendations encompass themes related to the development of a patient-centered research question, designing a study, disseminating RWE, and general considerations. For example, consider how patient input can inform population/subgroups, comparators, and study period. Researchers can leverage existing information describing PED and may be able to apply those insights to studies relying on traditional RWD sources and/or patient registries. CONCLUSIONS: Applying these emerging recommendations may improve the patient centricity of RWE through improved relevance of RWE to patient communities of interest and foster greater multidisciplinary participation and transparency in RWD research. As researchers gather experience by applying the methods recommendations, further refinement of these consensus recommendations may lead to "best practices."

Challenges in Research and Health Technology Assessment of Rare Disease Technologies: Report of the ISPOR Rare Disease Special Interest Group.

BACKGROUND: Successful development of new treatments for rare diseases (RDs) and their sustainable patient access require overcoming a series of challenges related to research and health technology assessment (HTA). These impediments, which may be unique to RDs or also apply to common diseases but are particularly pertinent in RDs, are diverse and interrelated. OBJECTIVE: To develop for the first time a catalog of primary impediments to RD research and HTA, and to describe the cause and effect of individual challenges. METHODS: Challenges were identified by an international 22-person expert working group and qualitative outreach to colleagues with relevant expertise. A broad range of stakeholder perspectives is represented. Draft results were presented at annual European and North American International Society for Pharmacoeconomics and Outcomes Research (ISPOR) congresses, and written comments were received by the 385-strong ISPOR Rare Disease Review Group from two rounds of review. Findings were refined and confirmed via targeted literature search. RESULTS: Research-related challenges linked to the low prevalence of RDs were categorized into those pertaining to disease recognition and diagnosis, evaluation of treatment effect, and patient recruitment for clinical research. HTA-related challenges were classified into issues relating to the lack of a tailored HTA method for RD treatments and uncertainty for HTA agencies and health care payers. CONCLUSIONS: Identifying and highlighting diverse, but interrelated, key challenges in RD research and HTA is an essential first step toward developing implementable and sustainable solutions. A collaborative multistakeholder effort is required to enable faster and less costly development of safe, efficacious, and appropriate new RD therapies that offer value for money.

Trends in management of pelvic organ prolapse among female Medicare beneficiaries.

OBJECTIVE: In the last decade, many new surgical treatments have been developed to achieve less-invasive approaches to prolapse management. However, limited data exist on how the patterns of care for women with pelvic organ prolapse (POP) may have changed over the last decade, and whether mesh implantation techniques have influenced the type of specific compartment repair performed. We used a national data set to analyze the temporal trends in patterns of care for women with POP. STUDY DESIGN: Data were obtained from Public Use Files from the Centers for Medicare and Medicaid Services for a 5% random sample of national beneficiaries with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis of POP from 1999 through 2009. Current Procedural Terminology, 4th Edition and International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes were used to evaluate nonsurgical and surgical management trends for this cohort. Types of surgery were categorized by prolapse compartment and combinations of repairs. After 2005, when applicable codes became available, mesh or graft repairs were also analyzed. RESULTS: Over the study time period, the number of women with a diagnosis of POP in any 1 year in our 5% sample of Medicare beneficiaries remained relatively stable (range, 21,245-23,268 per year). Rates of pessary insertion were also consistent at 11-13% over the study period. Of the women with a prolapse diagnosis, 14-15% underwent surgical repair, and there was little change over time in surgical management patterns based on compartment. Most commonly, multiple compartments were repaired simultaneously. There was a rapid increase in mesh use such that in 2009, 41% of all women who underwent surgery (5.8% of the total cohort) had mesh or graft inserted in their repair. Hysterectomy rates for prolapse decreased over time. Rates of vault suspension at the time of hysterectomy for prolapse were low; however, they showed a relative increase over time (22% in 1999 to 26% in 2009). CONCLUSION: Patterns and rates of prolapse repairs remained relatively unchanged from 1999 through 2009, with an exception of a rapid rise in mesh use. These data suggest that the majority of mesh techniques were used for augmentation purposes only, but did not result in an increase in apical repairs performed in the United States. There remains a disappointingly low rate of vault suspension repairs concomitantly at time of hysterectomy for POP.

Characteristics and temporal trends in patient registries: focus on the life sciences industry, 1981-2012.

PURPOSE: Patient registries are used to monitor safety, examine real-world effectiveness, and may potentially contribute to comparative effectiveness research. To our knowledge, life sciences industry (LSI)-sponsored registries have not been systematically categorized. This study represents a first step toward understanding such registries over time. METHODS: Studies described as registries were identified in the ClinicalTrials.gov database. Characteristics from these registry records were abstracted and analyzed. RESULTS: Of 1202 registries identified, approximately 47% reported LSI sponsorship. These 562 LSI registries varied in focus: medical devices (n = 193, 34%), specific drugs (n = 173, 31%), procedures (n = 29, 5%), or particular diseases (n = 139, 25%). Thirty-three registries (<6%) evaluated pregnancy outcomes. The most common therapeutic area was cardiovascular (n = 234, 42%); others included endocrinology, immunology, oncology, musculoskeletal disorders, and neurology. The two most often measured outcomes were clinical effectiveness and safety, each of which appeared in 363/562 (65%) of LSI registries. Other outcomes included real-world clinical practice patterns (n = 122, 22%), patient-reported outcomes (n = 106, 19%), disease epidemiology/natural history (n = 69, 12%), and economic outcomes (n = 30, 5%). The number of LSI registries and their geographic diversity has increased over time. CONCLUSIONS: The LSI registries represent a substantial proportion of all patient registries documented in ClinicalTrials.gov. These prospective studies are growing in number and encompass diverse therapeutic areas and geographic regions. Most registries measure multiple outcomes and capture real-world data that may be unavailable through other study designs. This classification of LSI registries documents their use for studying heterogeneity of diseases, examining treatment patterns, measuring patient-reported outcomes, examining economic outcomes, and performing comparative effectiveness research.

Review of the impact of NNRTI-based HIV treatment regimens on patient-reported disease burden.

While the burden of HIV disease is well documented, the value of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy regimens in reducing patient burden is not well understood. The purpose of this study was to examine patient-reported health among those receiving NNRTI-based regimens to understand their incremental value in reducing the burden of HIV. We conducted a structured literature review using PubMed to identify NNRTI trials utilizing validated patient-reported outcome (PRO) instruments during 2005-2011. The search strategy included a PubMed search to identify relevant studies based on disease, instrument, PRO, and NNRTI medication terms; and a manual search of bibliographies of identified papers. Data abstracted from each study included study type, treatment regimen(s), and PRO results. Of 11 trials identified, 8 (73%) reported significance of changes in a PRO over time and 10 (91%) reported significance of PRO changes between groups. Several domains were assessed, with significant findings (between or within groups) observed in: physical health/well-being (n = 5), emotional status/well-being (n = 2), symptoms (n = 2), anxiety (n = 2), gastrointestinal upset (n = 2), psychological health (n = 1), functional and global well-being (n = 1), fatigue/energy (n = 1), depression (n = 1), change in body appearance (n = 1), pain (n = 1), headache (n = 1), bad dreams/nightmares (n = 1), problems having sex (n = 1), and general health perception (n = 1). In conclusion, NNRTIs have been observed most frequently to improve patient-reported physical health and well-being. Treatments are needed that can also reduce patient burden in areas of emotional well-being, cognitive functioning, and overall symptom profile.

Responsiveness of the MOS-HIV and EQ-5D in HIV-infected adults receiving antiretroviral therapies.

BACKGROUND: Selection of an appropriate patient-reported outcome (PRO) instrument for a clinical trial requires knowledge of the instrument's responsiveness to detecting treatment effects. The purpose of this study was to examine the responsiveness of two health-related quality of life (HRQL) instruments used in clinical trials involving HIV-infected adults: the HIV-targeted Medical Outcomes Study HIV Health Survey (MOS-HIV), and a generic measure, the EuroQol-5D (EQ-5D). METHODS: A systematic review identified clinical trials using the MOS-HIV or EQ-5D to assess outcomes for HIV-infected adults. Data abstracted from each study included study type, treatment regimen(s), PRO results, and effect size (either reported or calculated). Effect size was calculated as the difference between baseline and follow-up mean scores divided by the baseline standard deviation. Magnitude was categorized as small (d=0.20), medium (d=0.50), and large (d=0.80). RESULTS: Between 2005 and 2010, the MOS-HIV was administered in 12 trials. Significant differences were observed between groups and over time in physical health summary (PHS) and mental health summary (MHS) scores (P<0.05) in subjects switching therapy after experiencing Grade-2 adverse events. Effect sizes were medium (0.55 and 0.49 for PHS and MHS, respectively) among treatment-naïve adults beginning therapy (two studies), but negligible among treatment-experienced adults (0.04 and 0.13 for PHS and MHS, respectively; three studies). The EQ-5D was used in five trials between 2001 and 2010. It was responsive to occurrences of adverse events and opportunistic infections, with small-to-medium effect sizes (range 0.30-0.50) in each of its five dimensions. CONCLUSIONS: A systematic review of PRO study results showed both the MOS-HIV and EQ-5D were responsive to changes between groups and/or over time in treatment-naïve HIV-infected patients. These instruments may be used either individually or together in clinical trials to measure changes in HRQL.

Patient reported outcome instruments used in clinical trials of HIV-infected adults on NNRTI-based therapy: a 10-year review.

BACKGROUND: Patient-reported outcomes (PROs) may provide valuable information to clinicians and patients when choosing initial antiretroviral therapy. OBJECTIVE: To identify and classify PRO instruments used to measure treatment effects in clinical trials evaluating NNRTIs. METHODS: We conducted a structured literature review using PubMed to identify NNRTI trials published from March 2003 to February 2013. Studies identified--based on disease, instrument, PRO, and NNRTI medication terms were reviewed--to identify PRO instruments. Domains measured within each instrument were recorded to understand key areas of interest in NNRTIs. RESULTS: Of 189 articles reviewed, 27 validated instruments were administered in 26 unique trials, with a mean of 1.9 instruments (median: 1; range: 1-7) per trial. The Medical Outcomes Study HIV Health Survey (MOS-HIV) was the most commonly used instrument (n = 8 trials). Seventeen trials (65%) included at least one multidimensional health-related quality of life (HRQL) instrument (HIV-targeted, n = 11; general, n = 8). Other validated instruments measured sleep (n = 5), depression (n = 5), anxiety (n = 4), psychiatric symptoms (n = 2), beliefs about HIV medications (n = 2), HIV symptoms (n = 1), and stress (n = 1). CONCLUSIONS: Although review of recent NNRTI trials suggests a lack of consensus on the optimal PRO instruments, a typical battery is comprised of a multidimensional HRQL measure coupled with one or more symptom measures. Further work is needed to clarify advantages and disadvantages of using specific PRO instruments to measure relevant constructs and to identify the most useful batteries of instruments for NNRTI trials.

Association of health-related quality of life with gender in patients with B-cell chronic lymphocytic leukemia.

PURPOSE: This analysis examined associations between gender and health-related quality of life (HRQOL) in patients with B-cell chronic lymphocytic leukemia (CLL) as they initiate therapy for CLL outside the clinical trial setting. METHODS: Baseline data were collected as part of Connect® CLL Registry, a prospective observational study initiated in community, academic, and government centers. Patient demographics and clinical characteristics were provided by clinicians. Patients reported HRQOL using the Brief Fatigue Inventory (BFI), EQ-5D, and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). Mean scores were analyzed, with statistical significance of differences determined by ANOVA. Multivariate analysis also considered age and line of therapy. RESULTS: Baseline HRQOL data were available for 1,140 patients: 710 (62 %) men and 430 (38 %) women from 161 centers. Patients were predominantly white (89 %) with mean age 69 ± 11 years. Women reported significantly worse global fatigue (P <0.0001), fatigue severity (P <0.0001), and fatigue-related interference (P = 0.0005) versus men (BFI). Pain/discomfort (P = 0.0077), usual activities (P = 0.0015), and anxiety/depression (P = 0.0117) were significantly worse in women than in men (EQ-5D). With women reporting a better social/family score (P = 0.0238) and men reporting a better physical score (P = 0.0002), the mean FACT-G total score did not differ by gender. However, the mean FACT-Leu total score was better among men versus women (P = 0.0223), primarily because the mean leukemia subscale score was significantly better among men (P <0.0001). Multivariate analysis qualitatively confirmed these findings. CONCLUSIONS: Connect® CLL Registry results indicate that significant differences exist in certain HRQOL domains, as women reported greater levels of fatigue and worse functioning in physical domains.

Comparative outcomes of open versus laparoscopic sacrocolpopexy among Medicare beneficiaries.

INTRODUCTION AND HYPOTHESIS: Since the first reported laparoscopic sacrocolpopexy in 1991, a limited number of single-center studies have attempted to assess the procedure's effectiveness and safety. Therefore, we analyzed a national Medicare database to compare real-world short-term outcomes of open and laparoscopically assisted (including robotic) sacrocolpopexy in a United States sample of patients. METHODS: Public Use File data for a 5% random national sample of all Medicare beneficiaries aged 65 and older were obtained from the Centers for Medicare and Medicaid Services for the years 2004-2008. Women with pelvic organ prolapse were identified using ICD-9 diagnosis codes. CPT-4 procedure codes were used to identify women who underwent open (code 57280) or laparoscopic (code 57425) sacrocolpopexy. Individual subjects were followed for 1 year post-operatively. Outcomes measured, using ICD-9 and CPT-4 codes, included medical and surgical complications and re-operation rates. RESULTS: Seven hundred and ninety-four women underwent open and 176 underwent laparoscopic (including robotic) sacrocolpopexy. Laparoscopic sacrocolpopexy was associated with a significantly increased rate of re-operation for anterior vaginal wall prolapse (3.4% vs 1.0%, p = 0.018). However, more medical (primarily cardiopulmonary) complications occurred post-operatively in the open group (31.5% vs 22.7%, p = 0.023). When sacrocolpopexy was performed with concomitant hysterectomy, mesh-related complications were significantly higher in the laparoscopic group (5.4% vs 0%, p = 0.026). CONCLUSION: Laparoscopic sacrocolpopexy resulted in an increased rate of reoperation for prolapse in the anterior compartment. When hysterectomy was performed at the time of sacrocolpopexy, the laparoscopic approach was associated with an increased risk of mesh-related complications.

Examining Endpoint Concordance in Clinical Trials and Real-World Clinical Practice to Advance Real-World Evidence Utilization.

Real-world evidence (RWE) is increasingly contributing to more informed decisions regarding the optimal access to and use of therapeutics to improve patient outcomes. However, in many cases, a disconnect between evidence derived from clinical trials and the RWE that follows market approval impedes the potential value and widespread adoption of RWE to optimize patient care. Collaborators with the Learning Ecosystems Accelerator for Patient-centered, Sustainable innovation (LEAPS), a major project of the Tufts Medical Center [formally Massachusetts Institute of Technology (MIT)] NEW Drug Development ParadIGmS (NEWDIGS) initiative, propose assessing the relationship between efficacy endpoints used in randomized controlled trials (RCTs) and effectiveness measures that inform treatment decisions within real-world clinical settings as one way to bridge this divide and further leverage RWE to improve care and patient outcomes. This commentary outlines elements of an endpoint concordance study using Rheumatoid Arthritis as a case study. The authors describe the ways in which better understanding of the relationship between effectiveness and RCT endpoints could improve the confidence in and adoption of RWE by both contextualizing existing RWE as well as identifying ways in which to improve the value of RWE in improving care and outcomes.

Extending the vision of adaptive point-of-care platform trials to improve targeted use of drug therapy regimens: An agile approach in the learning healthcare system toolkit.

OBJECTIVES: Improving the targeted use of drug regimens requires robust real-world evidence (RWE) to address the uncertainties that remain regarding their real-world performance following market entry. However, challenges in the current state of RWE production limit its impact on clinical decisions, as well as its operational scalability and sustainability. We propose an adaptive point-of-care (APoC) platform trial as an approach to RWE production that improves both clinical and operational efficiencies. METHODS AND FINDINGS: We explored design innovations, operational challenges, and infrastructure needs within a multi-stakeholder consortium to evaluate the potential of an APoC platform trial for studying chronic disease treatment regimens using rheumatoid arthritis as a case study. The concept integrates elements from adaptive clinical trials (dynamic treatment regimen strategies) and point-of-care trials (research embedded into routine clinical care) under a perpetual platform infrastructure. The necessary components to implement an APoC platform trial within outpatient settings exist, and present an opportunity for a cross-disciplinary, multi-stakeholder approach. Effective engagement of key stakeholders involved in and impacted by the platform is critical to success. Our collaborative design process identified three high-impact stakeholder-engagement areas: (1) focus on research question(s), (2) design and implementation planning such that it is feasible and fit-for-purpose, and (3) measurement, or meaningful metrics for both clinical (patient outcomes) and system (operational efficiencies) impact. CONCLUSIONS: An APoC platform trial for rheumatoid arthritis integrating innovative design elements in a scalable infrastructure has the potential to reduce important uncertainties about the real-world performance of biomedical innovations and improve clinical decisions.

Patient-reported treatment burden of chronic immune thrombocytopenia therapies.

BACKGROUND: Chronic immune thrombocytopenia (ITP) is a debilitating autoimmune disorder that causes a reduction in blood platelets and increased risk of bleeding. ITP is currently managed with various pharmacologic therapies and splenectomy.This study was conducted to assess patient perceived and reported treatment side effects, as well as the perceived burden or bother, and need to reduce or stop treatment, associated with these side effects among adult patients with chronic ITP. METHODS: A Web-enabled survey was administered to members of a US-based ITP patient support group. Patients reported demographic and clinical characteristics, ITP treatments' side effects for treatments received since diagnosed, level of bother (or distress), and need to reduce or stop treatment, associated with side effects. Current and past exposure was assessed for five specific treatment types: corticosteroids (CS), intravenous immunoglobulin (IVIg), anti-D immunoglobulin (anti-D), rituximab (RT), and splenectomy (SPL), as well as for other patient-referenced therapies (captured as "other"). RESULTS: The survey was completed by 589 patients; 78% female, 89% white, mean age 48 years (SD = 14.71), and 68% reported a typical low platelet count of < 50,000/µL. Current or past treatment with CS was reported by 92% (n = 542) of patients, 56% (n = 322) for IVIg, 36% (n = 209) for anti-D, 36% (n = 213) for RT, and 39% (n = 227) for SPL. A substantial proportion of CS-treated patients reported side effects (98%, P < 0.05), were highly bothered by their side effects (53.1%, P < 0.05), and reported the need to stop or reduce treatment due to side effects (37.8%, P < 0.05). Among patients reporting side effects of treatment, significant associations were noted for the number of side effects, aggregate bother of reported side effects, and the need to stop or reduce treatment (all P < 0.05). CONCLUSIONS: Current ITP treatments, particularly corticosteroids, are associated with multiple bothersome side effects that may lead to patients stopping or reducing therapy. Open, informed and complete communication between clinician and patient regarding both the benefits and the side effects of ITP treatment may better prepare patients for their prescribed regimens.

Predicting waist circumference from body mass index.

BACKGROUND: Being overweight or obese increases risk for cardiometabolic disorders. Although both body mass index (BMI) and waist circumference (WC) measure the level of overweight and obesity, WC may be more important because of its closer relationship to total body fat. Because WC is typically not assessed in clinical practice, this study sought to develop and verify a model to predict WC from BMI and demographic data, and to use the predicted WC to assess cardiometabolic risk. METHODS: Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES) and the Atherosclerosis Risk in Communities Study (ARIC). We developed linear regression models for men and women using NHANES data, fitting waist circumference as a function of BMI. For validation, those regressions were applied to ARIC data, assigning a predicted WC to each individual. We used the predicted WC to assess abdominal obesity and cardiometabolic risk. RESULTS: The model correctly classified 88.4% of NHANES subjects with respect to abdominal obesity. Median differences between actual and predicted WC were -0.07 cm for men and 0.11 cm for women. In ARIC, the model closely estimated the observed WC (median difference: -0.34 cm for men, +3.94 cm for women), correctly classifying 86.1% of ARIC subjects with respect to abdominal obesity and 91.5% to 99.5% as to cardiometabolic risk.The model is generalizable to Caucasian and African-American adult populations because it was constructed from data on a large, population-based sample of men and women in the United States, and then validated in a population with a larger representation of African-Americans. CONCLUSIONS: The model accurately estimates WC and identifies cardiometabolic risk. It should be useful for health care practitioners and public health officials who wish to identify individuals and populations at risk for cardiometabolic disease when WC data are unavailable.

Outcomes of erythropoiesis-stimulating agents in cancer patients with chemotherapy-induced anemia.

PURPOSE: To assess the clinical and economic outcomes among patients with chemotherapy-induced anemia (CIA) treated with United States Food and Drug Administration-approved fixed dosing regimens of erythropoiesis-stimulating agents (ESA). METHODS: Data were employed from the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) registry to evaluate CIA patients who were initiated on either epoetin alfa (EPO) 40,000 Units (U) or darbepoetin alfa (DARB) 500 micrograms (mcg) between January 1, 2006 and May 8, 2009. Study measurements included ESA treatment dose and dose ratio, changes in hemoglobin (Hb) levels from baseline, and cumulative ESA costs. RESULTS: Five hundred forty patients treated in 44 clinical centers were evaluated, of which 420 were initiated on EPO 40,000 U and 120 were initiated on DARB 500 mcg. Both cohorts had similar baseline characteristics, although EPO patients were less likely than DARB patients to have received iron supplementation before ESA initiation (11.4% EPO vs. 20.0% DARB, p = 0.015). The EPO-to-DARB dose ratio based on cumulative ESA dose was 169:1 (U EPO: mcg DARB). EPO patients showed statistically greater Hb improvement compared to DARB patients, and compared to EPO patients, a greater proportion of DARB patients required a blood transfusion (13.9% EPO vs. 22.5% DARB, p = 0.026). Mean cumulative ESA cost was significantly lower for EPO patients than DARB patients ($4,261 EPO vs. $8,643 DARB, p < 0.0001). CONCLUSIONS: These findings reported that patients with CIA achieved more favorable clinical and economic outcomes if initiated with EPO 40,000 U vs. DARB 500 mcg.

Maintenance and Concomitant Therapy Use with Chlormethine Gel Among Patients with Stage IA/IB Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma (MF-CTCL): A Real-World Evidence Study.

INTRODUCTION: Chlormethine (CL) gel is a skin-directed therapy approved for treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in the USA. MF-CTCL has a chronic clinical course, requiring long-term maintenance therapy with one or more therapies. This analysis describes real-world patterns of maintenance therapy and use of concomitant therapy with CL gel among patients with stage IA/IB MF-CTCL. METHODS: In a US-based registry, MF-CTCL patients treated with CL gel were enrolled between 3/2015 and 10/2018 across 46 centers and followed for up to 2 years. Patient demographics, clinical characteristics, CL gel treatment patterns, concomitant treatments, clinical response, and adverse events (AEs) were collected from medical records. Descriptive statistics are reported. RESULTS: Of the 206 patients with stage IA/IB MF-CTCL, 58.7% were male, and average age was 60.7 years with 4.6 years since diagnosis. Topical steroids, phototherapy, and topical retinoids were used concomitantly with CL gel in 62.6%, 26.2%, and 6.3% of patients, respectively. Most concomitant therapies (up to 85%) were started before CL gel initiation and, in about half of the cases (up to 57%), were used concurrently for ≥ 12 months. Overall, 158 (76.7%) patients experienced partial response (PR) and 144 continued with maintenance therapy. After achieving PR, most patients (74.3%) kept the same maintenance therapy schedule, most commonly once daily. Of patients who had any skin-related AE (31.6%) or skin-related AEs associated with CL gel (28.2%), nearly half experienced CL gel treatment interruption and ~40% had a dosing reduction. The observed real-world treatment patterns were concordant with National Comprehensive Cancer Network (NCCN) guidelines. CONCLUSION: The study results suggest that continuing CL gel maintenance therapy and combining treatments with CL gel are common practice in the real-world setting, with most maintained on a stable dosing schedule. Careful management of AEs may help patients maintain long-term optimal dosing with less treatment interruptions and dosing reductions.

The Current Landscape and Emerging Applications for Real-World Data in Diagnostics and Clinical Decision Support and its Impact on Regulatory Decision Making.

Real-world data (RWD) and real-world evidence (RWE) are becoming essential tools for informing regulatory decision making in health care and offer an opportunity for all stakeholders in the healthcare ecosystem to evaluate medical products throughout their lifecycle. Although considerable interest has been given to regulatory decisions supported by RWE for treatment authorization, especially in rare diseases, less attention has been given to RWD/RWE related to in vitro diagnostic (IVD) products and clinical decision support systems (CDSS). This review examines current regulatory practices in relation to IVD product development and discusses the use of CDSS in assisting clinicians to retrieve, filter, and analyze patient data in support of complex decisions regarding diagnosis and treatment. The review then explores how utilizing RWD could augment regulatory body understanding of test performance, clinical outcomes, and benefit-risk profiles, and how RWD could be leveraged to augment CDSS and improve safety, quality, and efficiency of healthcare practices. Whereas we present examples of RWD assisting in the regulation of IVDs and CDSS, we also highlight key challenges within the current healthcare system which are impeding the potential of RWE to be fully realized. These challenges include issues such as data availability, reliability, accessibility, harmonization, and interoperability, often for reasons specific to diagnostics. Finally, we review ways that these challenges are actively being addressed and discuss how private-public collaborations and the implementation of standardized language and protocols are working toward producing more robust RWD and RWE to support regulatory decision making.

Bridging the Gap Between RCTs and RWE Through Endpoint Selection.

This commentary is authored by several industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of Industry Leaders who have come together as non-competitive partners to understand and respond to RWD/E challenges and opportunities with a single expert voice. Here, the forum discusses the value in bridging the industry disconnect between RTCs and RWE, with a view to promoting the use of RWE in the RCT environment. RCT endpoints are explored along several axes including their clinical relevance and their measure of direct patient benefit, and then compared with their real-world counterparts to identify suitable paths, or gaps, for assimilating RWE endpoints into the RCT environment.

Strengthening pharma's contract with society: the value of trusted partnerships between pharma and healthcare facilitated by real-world data.

This White Paper is authored by 11 industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of industry leaders who come together as noncompetitive partners to understand and respond to internal or external RWD/E challenges and opportunities with a single expert voice. Herein we aim to clarify the rules of engagement between pharma and healthcare in order to establish trust-based partnerships, which will unlock unique value for society, including the medical community and the ultimate beneficiary, the patient.

Prediction of first events of coronary heart disease and stroke with consideration of adiposity.

BACKGROUND: Prediction of coronary heart disease (CHD) and cerebrovascular disease (CeVD) can aid healthcare providers and prevention programs. Previous reports have focused on traditional cardiovascular risk factors; less information has been available on the role of overweight and obesity. METHODS AND RESULTS: Baseline data from 4780 Framingham Offspring Study adults with up to 24 years of follow-up were used to assess risk for a first CHD event (angina pectoris, myocardial infarction, or cardiac death) alone, first CeVD event (acute brain infarction, transient ischemic attack, and stroke-related death) alone, and CHD and CeVD events combined. Accelerated failure time models were developed for the time of first event to age, sex, cholesterol, high-density lipoprotein cholesterol, diabetes mellitus (DM), systolic blood pressure, smoking status, and body mass index (BMI). Likelihood-ratio tests of statistical significance were used to identify the best-fitting predictive functions. Age, sex, smoking status, systolic blood pressure, ratio of cholesterol to high-density lipoprotein cholesterol, and presence of DM were highly related (P<0.01 for all) to the development of first CHD events, and all of the above except sex and DM were highly related to the first CeVD event. BMI also significantly predicted the occurrence of CHD (P=0.05) and CeVD (P=0.03) in multivariable models adjusting for traditional risk factors. The magnitude of the BMI effect was reduced but remained statistically significant when traditional variables were included in the prediction models. CONCLUSIONS: Greater BMI, higher systolic blood pressure, higher ratio of cholesterol to high-density lipoprotein cholesterol, and presence of DM were all predictive of first CHD events, and all but the presence of DM were predictive of first CeVD events. These results suggest that common pathophysiological mechanisms underlie the roles of BMI, DM, and systolic blood pressure as predictors for first CHD and CeVD events.