Regulatory and HTA Considerations for Development of Real-World Data Derived External Controls.

Regulators and Health Technology Assessment (HTA) bodies are increasingly familiar with, and publishing guidance on, external controls derived from real-world data (RWD) to generate real-world evidence (RWE). We recently conducted a systematic literature review (SLR) evaluating publicly available information on the use of RWD-derived external controls to contextualize outcomes from uncontrolled trials submitted to the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and/or select HTA bodies. The review identified several key operational and methodological aspects for which more detailed guidance and alignment within and between regulatory agencies and HTA bodies is necessary.

Assessing the incidence of osteosarcoma among teriparatide-treated patients using linkage of commercial pharmacy and state cancer registry data, contributing to the removal of boxed warning and other labeling changes.

Background: Teriparatide, a recombinant human parathyroid hormone analogue, is associated with increased bone mineral density and a decreased risk of fractures. A dose-dependent increase in the incidence of osteosarcoma was observed in toxicology studies conducted in rats. The primary objective of this study was to estimate the incidence of osteosarcoma over a 10-year period among teriparatide-treated patients versus patients unexposed to teriparatide with osteoporosis and patients in the general population using national pharmacy dispensing data linked with data from participating state cancer registries (SCRs) in the US.

Real-world cohort study of adult and pediatric patients treated for hereditary angioedema in the United States.

There is limited real-world evidence on hereditary angioedema (HAE) patient characteristics and health-care resource utilization (HCRU); in addition, pediatric patients have been described in small cohorts. To describe patient characteristics, treatment patterns, and HCRU among adult and pediatric patients treated for HAE in a large U.S.

Awareness of, and Compliance with, Domperidone Revised Labeling After a Risk-Minimization Activity in Europe.

Background And Objective: Risk-minimization measures (RMM), including label revisions were implemented in Europe for domperidone because of evidence of increased incidence of cardiac arrhythmia and sudden cardiac death. In accordance with the guideline on good pharmacovigilance practices, the European Medicines Agency Pharmacovigilance Risk Assessment Committee requested to conduct two studies to evaluate the effectiveness of these risk minimization measures.

Methods: In Belgium, France, Germany, Spain, and the UK, surveys were conducted to assess physicians' knowledge on the updated domperidone labeling information, and a drug-utilization study (DUS) was conducted using healthcare databases to assess domperidone prescribing patterns before and after the RMM.

Validating an algorithm for multiple myeloma based on administrative data using a SEER tumor registry and medical record review.

Purpose: Large numbers of multiple myeloma patients can be studied in real-world clinical settings using administrative databases. The validity of these studies is contingent upon accurate case identification. Our objective was to develop and evaluate algorithms to use with administrative data to identify multiple myeloma cases.

Treatment patterns, adherence, and persistence among psoriasis patients treated with biologics in a real-world setting, overall and by disease severity.

Purpose: Describe treatment patterns by disease severity among biologic-treated psoriasis patients.

Materials And Methods: We selected our study cohort in the IQVIA PharMetrics Plus adjudicated claims database linked to Electronic Health Record data from Modernizing Medicine Data Services. Patients were classified as having mild, moderate, or severe psoriasis based on a hierarchy of available severity measures.

Healthcare resource utilization and costs among psoriasis patients treated with biologics, overall and by disease severity.

Aims: To describe healthcare resource utilization (HCRU) and costs among biologic-treated psoriasis patients in the US, overall and by disease severity.

Materials And Methods: IQVIA PharMetrics Plus administrative claims data were linked with Modernizing Medicine Data Services Electronic Health Record data and used to select adult psoriasis patients between April 1, 2010 and December 31, 2014. Eligible patients were classified by disease severity (mild, moderate, severe) using a hierarchy of available clinical measures.

Melanoma Thickness and Survival Trends in the United States, 1989 to 2009.

Background: With melanoma incidence rising and mortality stable, some question whether the melanoma epidemic is real. Melanoma thickness and survival trends may provide insights, but previous studies have been limited because of missing data on thickness.

Methods: With a validated imputation method for missing thickness data, we characterized melanoma thickness and survival trends among men and women in the Surveillance, Epidemiology, and End Results (SEER)-9 registries between 1989 and 2009.

Sunburn, sun exposure, and sun sensitivity in the Study of Nevi in Children.

Purpose: To examine the joint effect of sun exposure and sunburn on nevus counts (on the natural logarithm scale; log nevi) and the role of sun sensitivity.

Methods: We describe an analysis of cross-sectional data from 443 children enrolled in the prospective Study of Nevi in Children. To evaluate the joint effect, we partitioned the sum of squares because of interaction between sunburn and sun exposure into orthogonal components representing (1) monotonic increase in log nevi with increasing sun exposure (rate of increase of log nevi depends on sunburn), and (2) nonmonotonic pattern.

Dermatoscopic imaging of skin lesions by high school students: a cross-sectional pilot study.

Background: The ability of novices to perform imaging of skin lesions is not well studied.

Objectives: To determine the ability of 12th grade high school students without formal training to take clinical and dermatoscopic images of skin lesions on patient-actors.

Patients/methods: Nineteen participants were divided into 11 gender-specific groups of 1-2 students.

Incidence of liver injury among cancer patients receiving chemotherapy in an integrated health system.

Purpose: Using liver laboratory tests (LLTs), Hy's law is a method used to identify drug-induced liver injury (DILI), after excluding other causes. Elevated LLTs in chemotherapy-exposed patients may result from tumor effects or comorbidities. This study evaluated incidence of Hy's law in chemotherapy-treated cancer patients.

Feasibility and Efficacy of Patient-Initiated Mobile Teledermoscopy for Short-term Monitoring of Clinically Atypical Nevi.

Importance: Patient-driven mobile teledermoscopy may be applicable for monitoring of skin lesions.

Objective: To assess the feasibility, efficacy, and patient receptivity of teledermoscopy for short-term monitoring of clinically atypical nevi.

Design, Setting, And Participants: This was a prospective cohort study performed at an institutional referral center in New York.

Tanning and beauty: Mother and teenage daughters in discussion.

Tanning increases dramatically through the teenage years, but the family context of this health risk behavior is relatively unstudied. We conducted videotaped conversations between teenage girls (10th and 11th grade) and their mothers. We developed a coding system for discussion content and highlight findings including inadequate knowledge concerning the harms of tanning and positive views of outdoor tanning over indoor tanning, yet agreement that all tans are attractive.

Patient characteristics and participation in a genetic study: a type 2 diabetes cohort.

Background: Recruitment of large, diverse populations into genetic studies remains challenging. Potential strategies to overcome limitations include leveraging electronic health data and minimizing patient burden. We sought to describe the overall participation rate and identify characteristics associated with participation in a genetic substudy of patients with type 2 diabetes mellitus, in which patients were identified via electronic hospital data and asked to participate by providing DNA samples by mail.

Patient perceptions of nonmelanoma skin cancer before diagnosis.

Background: There is a paucity of data regarding patient perceptions of nonmelanoma skin cancer (NMSC).

Objective: To describe patients' perceptions of skin lesions before a diagnosis of NMSC.

Methods: This was a descriptive study in a private practice setting.

Melanoma survivors: health behaviors, surveillance, psychosocial factors, and family concerns.

Background: Little research has been conducted on melanoma survivors and important opportunities exist for research in this understudied population. The study objective was to examine experiences of melanoma survivors regarding sun protection, surveillance practices, psychosocial and family concerns using focus groups.

Methods: We identified patients (≥ 18 years) treated at Memorial Sloan-Kettering Cancer Center (USA) during 1996-2005 with invasive primary cutaneous melanoma, stages I-III.

The characterization and potential impact of melanoma cases with unknown thickness in the United States' Surveillance, Epidemiology, and End Results Program, 1989-2008.

Background: In the United States, the Surveillance, Epidemiology, and End Results (SEER) Program is the authoritative source for population-based data on melanoma incidence and mortality. However, missing data on tumor thickness may lead to biased analyses in this frequently used database. We sought to characterize invasive melanomas with unknown thickness with emphasis on their association with melanoma survival, and to employ techniques to overcome the limitations of missing data on tumor thickness.

Cardiovascular outcomes in women with advanced breast cancer exposed to chemotherapy.

Purpose: To quantify incidence of cardiovascular outcomes in patients with advanced breast cancer receiving cardiotoxic and non-cardiotoxic chemotherapy.

Methods: This study identified all women at a Midwestern health system with initial diagnosis of American Joint Commission on Cancer Stage III/IV breast cancer (1995-2003) and random sample of 50 women initially diagnosed with Stage I/II who progressed to Stage III/IV. The rate of new cardiovascular outcomes (heart failure, dysrhythmia, and ischemia events) for cardiotoxic (anthracycline or trastuzumab) and non-cardiotoxic agents was calculated.

Prospective study of sunburn and sun behavior patterns during adolescence.

Objectives: Early childhood UV light radiation (UVR) exposures have been shown to be associated with melanoma development later in life. The objective of this study was to assess sunburn and changes in sunburn and sun behaviors during periadolescence.

Methods: A prospective, population-based study was conducted in fifth-grade children (∼10 years of age) from Framingham, Massachusetts.

Communication about family members' risk of melanoma: self-reported practices of dermatologists in the United States.

Objectives: To assess current self-reported communication and screening practices of dermatologists to their patients with melanoma about family members' risk of melanoma at the time of diagnosis and to understand the barriers that dermatologists encounter in communicating risk to patients.

Design: Descriptive survey study.

Setting: Office-based practicing physicians in the United States.