Mimicking Clinical Trials Using Real-World Data: A Novel Method and Applications.

Introduction: Simulating individual-level trial data when only summary data are available is often useful for meta-analysis, forming external control arms and calibrating trial results to real-world data (RWD). The joint distribution of baseline characteristics in a trial is usually simulated by combining its summary data with RWD's correlations. However, RWD correlations may not be a perfect proxy for the trial.

Analysis of population immunity to poliovirus following cessation of trivalent oral polio vaccine.

Background: The global withdrawal of trivalent oral poliovirus vaccine (OPV) (tOPV, containing Sabin poliovirus strains serotypes 1, 2 and 3) from routine immunization, and the introduction of bivalent OPV (bOPV, containing Sabin poliovirus strains serotypes 1 and 3) and trivalent inactivated poliovirus vaccine (IPV) into routine immunization was expected to improve population serologic and mucosal immunity to types 1 and 3 poliovirus, while population mucosal immunity to type 2 poliovirus would decline. However, over the period since tOPV withdrawal, the implementation of preventive bOPV supplementary immunization activities (SIAs) has decreased, while outbreaks of type 2 circulating vaccine derived poliovirus (cVDPV2) have required targeted use of monovalent type 2 OPV (mOPV2).

Methods: We develop a dynamic model of OPV-induced immunity to estimate serotype-specific, district-level immunity for countries in priority regions and characterize changes in immunity since 2016.

Racial Disparities in Access to Prostate Cancer Clinical Trials: A County-Level Analysis.

Background: African American men have a higher burden of prostate cancer compared with other populations. We sought to determine if they experience disparities in access to prostate cancer clinical trials.

Methods: We created a database of all US counties by linking prostate cancer clinical trial data with county-level socioeconomic, demographic, and health-care facility data derived from several external data sources.

Covasim: An agent-based model of COVID-19 dynamics and interventions.

The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes country-specific demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, long-term care facilities, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility.

Characterization of a Real-World Response Variable and Comparison with RECIST-Based Response Rates from Clinical Trials in Advanced NSCLC.

Introduction: Effectiveness metrics for real-word research, analogous to clinical trial ones, are needed. This study aimed to develop a real-world response (rwR) variable applicable to solid tumors and to evaluate its clinical relevance and meaningfulness.

Methods: This retrospective study used patient cohorts with advanced non-small cell lung cancer from a nationwide, de-identified electronic health record (EHR)-derived database.

Influence of Modeling Choices on Value of Information Analysis: An Empirical Analysis from a Real-World Experiment.

Background: Value of information (VOI) analysis often requires modeling to characterize and propagate uncertainty. In collaboration with a cancer clinical trial group, we integrated a VOI approach to assessing trial proposals.

Objective: This paper aims to explore the impact of modeling choices on VOI results and to share lessons learned from the experience.

Clinical exome sequencing vs. usual care for hereditary colorectal cancer diagnosis: A pilot comparative effectiveness study.

Background: Clinical exome sequencing (CES) provides the advantage of assessing genetic variation across the human exome compared to a traditional stepwise diagnostic approach or multi-gene panels. Comparative effectiveness research methods offer an approach to better understand the patient-centered and economic outcomes of CES.

Purpose: To evaluate CES compared to usual care (UC) in the diagnostic work-up of inherited colorectal cancer/polyposis (CRCP) in a randomized controlled trial (RCT).

How Does Option Value Affect the Potential Cost-Effectiveness of a Treatment? The Case of Ipilimumab for Metastatic Melanoma.

Background: Innovations that extend life can generate option value and cost of experiencing future technologies.

Objectives: To understand how consideration of option value may affect the potential cost-effectiveness of a treatment through a case study of ipilimumab for previously untreated metastatic melanoma.

Methods: We estimated the cost-effectiveness of ipilimumab in 2 scenarios: a conventional scenario, for which we constructed the model using the standard methods that rely on efficacy data directly from the phase III trial of ipilimumab, and an option value scenario, where we incorporated future hypothetical improvements in mortality for metastatic melanoma owing to innovations.

Do cancer treatments have option value? Real-world evidence from metastatic melanoma.

A change in the expectations about future treatments may change the option value of a current treatment, thereby affecting its utilization. We conducted an interrupted time series analysis using a large administrative claims database to test whether the utilization of existing cancer treatments changed after the disclosures of the then-investigational drug ipilimumab's Phase II and Phase III results among metastatic melanoma patients from 2008 to 2011. We used a multinomial logistic regression to analyze the temporal probability of receiving antineoplastic systemic therapy, surgical resection of metastasis, or both, relative to no treatment, in the first 3 months following the first metastasis diagnosis.

The Feelings About genomiC Testing Results (FACToR) Questionnaire: Development and Preliminary Validation.

The purpose of this study was to develop a brief instrument, the Feelings About genomiC Testing Results (FACToR), to measure the psychosocial impact of returning genomic findings to patients in research and clinical practice. To create the FACToR, we modified and augmented the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire based on findings from a literature review, two focus groups (N = 12), and cognitive interviews (N = 6). We evaluated data from 122 participants referred for evaluation for inherited colorectal cancer or polyposis from the New EXome Technology in (NEXT) Medicine Study, an RCT of exome sequencing versus usual care.

Integrating value of research into NCI Clinical Trials Cooperative Group research review and prioritization: A pilot study.

Background: The Institute of Medicine has called for approaches to help maximize the return on investments (ROI) in cancer clinical trials. Value of Research (VOR) is a health economics technique that estimates ROI and can inform research prioritization. Our objective was to evaluate the impact of using VOR analyses on the clinical trial proposal review process within the SWOG cancer clinical trials consortium.

Steady Increase In Prices For Oral Anticancer Drugs After Market Launch Suggests A Lack Of Competitive Pressure.

The cost of treating cancer has risen to unprecedented heights, putting tremendous financial pressure on patients, payers, and society. Previous studies have documented the rising prices of cancer drugs at launch, but less critical attention has been paid to the cost of these drugs after launch. We used pharmacy claims for commercially insured individuals to examine trends in postlaunch prices over time for orally administered anticancer drugs recently approved by the Food and Drug Administration (FDA).

Breast MRI in the Diagnostic and Preoperative Workup Among Medicare Beneficiaries With Breast Cancer.

Purpose: We compared the frequency and sequence of breast imaging and biopsy use for the diagnostic and preoperative workup of breast cancer according to breast magnetic resonance imaging (MRI) use among older women.

Materials And Methods: Using SEER-Medicare data from 2004 to 2010, we identified women with and without breast MRI as part of their diagnostic and preoperative breast cancer workup and measured the number and sequence of breast imaging and biopsy events per woman.

Results: A total of 10,766 (20%) women had an MRI in the diagnostic/preoperative period, 32,178 (60%) had mammogram and ultrasound, and 10,669 (20%) had mammography alone.

Development and Evaluation of an Approach to Using Value of Information Analyses for Real-Time Prioritization Decisions Within SWOG, a Large Cancer Clinical Trials Cooperative Group.

Objective: Value of information (VOI) analyses can align research with areas with the greatest potential impact on patient outcome, but questions remain concerning the feasibility and acceptability of these approaches to inform prioritization decisions. Our objective was to develop a process for calculating VOI in "real time" to inform trial funding decisions within SWOG, a large cancer clinical trials group.

Methods: We developed an efficient and scalable VOI modeling approach using a selected sample of 9 randomized phase II/III trial proposals from the Breast, Gastrointestinal, and Genitourinary Disease Committees reviewed by SWOG's leadership between 2008 and 2013.

Predicting Low Accrual in the National Cancer Institute's Cooperative Group Clinical Trials.

Background: The extent to which trial-level factors differentially influence accrual to trials has not been comprehensively studied. Our objective was to evaluate the empirical relationship and predictive properties of putative risk factors for low accrual in the National Cancer Institute's (NCI's) Cooperative Group Program, now the National Clinical Trials Network (NCTN).

Methods: Data from 787 phase II/III adult NCTN-sponsored trials launched between 2000 and 2011 were used to develop a logistic regression model to predict low accrual, defined as trials that closed with or were accruing at less than 50% of target; 46 trials opened between 2012 and 2013 were used for prospective validation.

Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and Polyposis Syndromes: A Cost-Effectiveness Analysis.

Purpose: To evaluate the cost effectiveness of next-generation sequencing (NGS) panels for the diagnosis of colorectal cancer and polyposis (CRCP) syndromes in patients referred to cancer genetics clinics.

Patients And Methods: We developed a decision model to evaluate NGS panel testing compared with current standard of care in patients referred to a cancer genetics clinic. We obtained data on the prevalence of genetic variants from a large academic laboratory and calculated the costs and health benefits of identifying relatives with a pathogenic variant, in life-years and quality-adjusted life-years (QALYs).

The cost-effectiveness of returning incidental findings from next-generation genomic sequencing.

Purpose: The American College of Medical Genetics and Genomics (ACMG) recommended that clinical laboratories performing next-generation sequencing analyze and return pathogenic variants for 56 specific genes it considered medically actionable. Our objective was to evaluate the clinical and economic impact of returning these results.

Methods: We developed a decision-analytic policy model to project the quality-adjusted life-years and lifetime costs associated with returning ACMG-recommended incidental findings in three hypothetical cohorts of 10,000 patients.

Comparative effectiveness of next generation genomic sequencing for disease diagnosis: design of a randomized controlled trial in patients with colorectal cancer/polyposis syndromes.

Whole exome and whole genome sequencing are applications of next generation sequencing transforming clinical care, but there is little evidence whether these tests improve patient outcomes or if they are cost effective compared to current standard of care. These gaps in knowledge can be addressed by comparative effectiveness and patient-centered outcomes research. We designed a randomized controlled trial that incorporates these research methods to evaluate whole exome sequencing compared to usual care in patients being evaluated for hereditary colorectal cancer and polyposis syndromes.

Return of incidental findings in genomic medicine: measuring what patients value--development of an instrument to measure preferences for information from next-generation testing (IMPRINT).

Purpose: Little is known about the factors that influence patients' preferences for the return of incidental findings from genome sequencing. This study identified attributes of incidental findings that were important to patients and developed a discrete-choice experiment instrument to quantify patient preferences.

Methods: An initial set of key attributes and attribute levels was developed from a literature review and in consultation with experts.

Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study.

Objective: To determine the association between concentration of prostate specific antigen (PSA) at age 40-55 and subsequent risk of prostate cancer metastasis and mortality in an unscreened population to evaluate when to start screening for prostate cancer and whether rescreening could be risk stratified.

Design: Case-control study with 1:3 matching nested within a highly representative population based cohort study.

Setting: Malmö Preventive Project, Sweden.

Who should be included in a clinical trial of screening for bladder cancer?: a decision analysis of data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Background: Because of its relatively low incidence, bladder cancer screening might have a better ratio of benefits to harms if it is restricted to a high-risk population. Data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial were used and simple decision analytic techniques were applied to compare different eligibility criteria for a screening trial.

Methods: For a variety of possible eligibility criteria, the percentage of the population aged 55 years to 74 years and classified as being at high risk for developing invasive or high-grade carcinoma, and therefore likely to benefit from screening, was calculated.

Individualized estimation of the benefit of radical prostatectomy from the Scandinavian Prostate Cancer Group randomized trial.

Background: Although there is randomized evidence that radical prostatectomy improves survival, there are few data on how benefit varies by baseline risk.

Objective: We aimed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient, using stage, grade, prostate-specific antigen, and age as predictors.

Design, Setting, And Participants: A total of 695 men with T1 or T2 prostate cancer participated in the Scandinavian Prostate Cancer Group 4 trial (SPCG-4).