Cost Effectiveness of Age-Specific Screening Intervals for People With Family Histories of Colorectal Cancer.

BACKGROUND & AIMS: Relative risk of colorectal cancer (CRC) decreases with age among individuals with a family history of CRC. However, no screening recommendations specify less frequent screening with increasing age. We aimed to determine whether such a refinement would be cost effective. METHODS: We determined the relative risk for CRC for individuals based on age and number of affected first-degree relatives (FDRs) using data from publications. For each number of affected FDRs, we used the Microsimulation Screening Analysis model to estimate costs and effects of colonoscopy screening strategies with different age ranges and intervals. Screening was then optimized sequentially, starting with the youngest age group, and allowing the interval of screening to change at certain ages. Strategies with an incremental cost effectiveness ratio below $100,000 per quality-adjusted life year were considered cost effective. RESULTS: For people with 1 affected FDR (92% of those with a family history), screening every 3 years beginning at an age of 40 years is most cost effective. If no adenomas are found, the screening interval can gradually be extended to 5 and 7 years, at ages 45 and 55 years, respectively. From a cost-effectiveness perspective, individuals with more affected FDRs should start screening earlier and at shorter intervals. However, frequency can be reduced if no abnormalities are found. CONCLUSIONS: Using a microsimulation model, we found that for individuals with a family history of CRC, it is cost effective to gradually increase the screening interval if several subsequent screening colonoscopies have negative results and no new cases of CRC are found in family members.

Family history and the natural history of colorectal cancer: systematic review.

PURPOSE: Family history of colorectal cancer (CRC) is a known risk factor for CRC and encompasses both genetic and shared environmental risks. METHODS: We conducted a systematic review to estimate the impact of family history on the natural history of CRC and adherence to screening. RESULTS: We found high heterogeneity in family-history definitions, the most common definition being one or more first-degree relatives. The prevalence of family history may be lower than the commonly cited 10%, and confirms evidence for increasing levels of risk associated with increasing family-history burden. There is evidence for higher prevalence of adenomas and of multiple adenomas in people with family history of CRC but no evidence for differential adenoma location or adenoma progression by family history. Limited data regarding the natural history of CRC by family history suggest a differential age or stage at cancer diagnosis and mixed evidence with respect to tumor location. Adherence to recommended colonoscopy screening was higher in people with a family history of CRC. CONCLUSION: Stratification based on polygenic and/or multifactorial risk assessment may mature to the point of displacing family history-based approaches, but for the foreseeable future, family history may remain a valuable clinical tool for identifying individuals at increased risk for CRC.

Evidence synthesis and guideline development in genomic medicine: current status and future prospects.

PURPOSE: With the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field. METHODS: To pursue a discussion of the minimal elements needed to develop evidence-based guidelines in genomics, the Centers for Disease Control and Prevention and the National Cancer Institute jointly held a workshop to engage representatives from 35 organizations with interest in genomics (13 of which make recommendations). The workshop explored methods used in evidence synthesis and guideline development and initiated a dialogue to compare these methods and to assess whether they are consistent with the Institute of Medicine report "Clinical Practice Guidelines We Can Trust." RESULTS: The participating organizations that develop guidelines or recommendations all had policies to manage guideline development and group membership, and processes to address conflicts of interests. However, there was wide variation in the reliance on external reviews, regular updating of recommendations, and use of systematic reviews to assess the strength of scientific evidence. CONCLUSION: Ongoing efforts are required to establish criteria for guideline development in genomic medicine as proposed by the Institute of Medicine.

Immunization information systems to increase vaccination rates: a community guide systematic review.

CONTEXT: Immunizations are the most effective way to reduce incidence of vaccine-preventable diseases. Immunization information systems (IISs) are confidential, population-based, computerized databases that record all vaccination doses administered by participating providers to people residing within a given geopolitical area. They facilitate consolidation of vaccination histories for use by health care providers in determining appropriate client vaccinations. Immunization information systems also provide aggregate data on immunizations for use in monitoring coverage and program operations and to guide public health action. EVIDENCE ACQUISITION: Methods for conducting systematic reviews for the Guide to Community Preventive Services were used to assess the effectiveness of IISs. Reviewed evidence examined changes in vaccination rates in client populations or described expanded IIS capabilities related to improving vaccinations. The literature search identified 108 published articles and 132 conference abstracts describing or evaluating the use of IISs in different assessment categories. EVIDENCE SYNTHESIS: Studies described or evaluated IIS capabilities to (1) create or support effective interventions to increase vaccination rates, such as client reminder and recall, provider assessment and feedback, and provider reminders; (2) determine client vaccination status to inform decisions by clinicians, health care systems, and schools; (3) guide public health responses to outbreaks of vaccine-preventable disease; (4) inform assessments of vaccination coverage, missed vaccination opportunities, invalid dose administration, and disparities; and (5) facilitate vaccine management and accountability. CONCLUSIONS: Findings from 240 articles and abstracts demonstrate IIS capabilities and actions in increasing vaccination rates with the goal of reducing vaccine-preventable disease.

Characterizing genetic variants for clinical action.

Genome-wide association studies, DNA sequencing studies, and other genomic studies are finding an increasing number of genetic variants associated with clinical phenotypes that may be useful in developing diagnostic, preventive, and treatment strategies for individual patients. However, few variants have been integrated into routine clinical practice. The reasons for this are several, but two of the most significant are limited evidence about the clinical implications of the variants and a lack of a comprehensive knowledge base that captures genetic variants, their phenotypic associations, and other pertinent phenotypic information that is openly accessible to clinical groups attempting to interpret sequencing data. As the field of medicine begins to incorporate genome-scale analysis into clinical care, approaches need to be developed for collecting and characterizing data on the clinical implications of variants, developing consensus on their actionability, and making this information available for clinical use. The National Human Genome Research Institute (NHGRI) and the Wellcome Trust thus convened a workshop to consider the processes and resources needed to: (1) identify clinically valid genetic variants; (2) decide whether they are actionable and what the action should be; and (3) provide this information for clinical use. This commentary outlines the key discussion points and recommendations from the workshop.

Decision-making process for conditions nominated to the recommended uniform screening panel: statement of the US Department of Health and Human Services Secretary's Advisory Committee on Heritable Disorders in Newborns and Children.

PURPOSE: The US Secretary of Health and Human Services provides guidance to state newborn screening programs about which conditions should be included in screening (i.e., the "Recommended Uniform Screening Panel"). This guidance is informed by evidence-based recommendations from the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. This report describes the Advisory Committee's revised decision-making process for considering conditions nominated to the panel. METHODS: An expert panel meeting was held in April 2012 to revise the decision matrix, which helps to guide the recommendation process. In January 2013, the Advisory Committee voted to adopt the revised decision matrix. RESULTS: The revised decision matrix clarifies the approach to rating magnitude and certainty of the net benefit of screening to the population of screened newborns for nominated conditions, and now includes the consideration of the capability of state newborn screening programs for population-wide implementation by evaluating the feasibility and readiness of states to adopt screening for nominated conditions. CONCLUSION: The revised decision matrix will bring increased quality, transparency, and consistency to the process of modifying the recommended uniform screening panel and will now allow formal evaluation of the challenges that state newborn screening programs face in adopting screening for new conditions.

Improving the efficiency and relevance of evidence-based recommendations in the era of whole-genome sequencing: an EGAPP methods update.

To provide an update on recent revisions to Evaluation of Genomic Applications in Practice and Prevention (EGAPP) methods designed to improve efficiency, and an assessment of the implications of whole genome sequencing for evidence-based recommendation development. Improvements to the EGAPP approach include automated searches for horizon scanning, a quantitative ranking process for topic prioritization, and the development of a staged evidence review and evaluation process. The staged process entails (i) triaging tests with minimal evidence of clinical validity, (ii) using and updating existing reviews, (iii) evaluating clinical validity prior to analytic validity or clinical utility, (iv) using decision modeling to assess potential clinical utility when direct evidence is not available. EGAPP experience to date suggests the following approaches will be critical for the development of evidence based recommendations in the whole genome sequencing era: (i) use of triage approaches and frameworks to improve efficiency, (ii) development of evidence thresholds that consider the value of further research, (iii) incorporation of patient preferences, and (iv) engagement of diverse stakeholders. The rapid advances in genomics present a significant challenge to traditional evidence based medicine, but also an opportunity for innovative approaches to recommendation development.

Lessons from the Electronic Data Methods Forum: collaboration at the frontier of comparative effectiveness research, patient-centered outcomes research, and quality improvement.

BACKGROUND: The Electronic Data Methods (EDM) Forum, with support from the Agency for Healthcare Research and Quality, exists to advance knowledge and practice on the use of electronic clinical data (ECD) for comparative effectiveness research, patient-centered outcomes research, and quality improvement (QI). The EDM Forum facilitates collaboration between the Prospective Outcome Systems using Patient-specific Electronic data to Compare Tests and therapies, Scalable Distributed Research Network, and Enhanced registry projects funded by Agency for Healthcare Research and Quality. OBJECTIVES: This overview describes a second set of papers commissioned by the EDM Forum, published in this supplement to Medical Care. The papers that are included discuss challenges and innovations from the research and QI community using ECD. CONCLUSIONS: The papers in this supplement provide lessons learned based on experiences building transparent, scalable, reusable networks for research and QI. Through these papers, and a new open access e-journal, eGEMs, the EDM Forum is working to advance the science of health research and QI using ECD to improve patient outcomes.

Population-based versus practice-based recall for childhood immunizations: a randomized controlled comparative effectiveness trial.

OBJECTIVES: We compared the effectiveness and cost-effectiveness of population-based recall (Pop-recall) versus practice-based recall (PCP-recall) at increasing immunizations among preschool children. METHODS: This cluster-randomized trial involved children aged 19 to 35 months needing immunizations in 8 rural and 6 urban Colorado counties. In Pop-recall counties, recall was conducted centrally using the Colorado Immunization Information System (CIIS). In PCP-recall counties, practices were invited to attend webinar training using CIIS and offered financial support for mailings. The percentage of up-to-date (UTD) and vaccine documentation were compared 6 months after recall. A mixed-effects model assessed the association between intervention and whether a child became UTD. RESULTS: Ten of 195 practices (5%) implemented recall in PCP-recall counties. Among children needing immunizations, 18.7% became UTD in Pop-recall versus 12.8% in PCP-recall counties (P < .001); 31.8% had documented receipt of 1 or more vaccines in Pop-recall versus 22.6% in PCP-recall counties (P < .001). Relative risk estimates from multivariable modeling were 1.23 (95% confidence interval [CI] = 1.10, 1.37) for becoming UTD and 1.26 (95% CI = 1.15, 1.38) for receipt of any vaccine. Costs for Pop-recall versus PCP-recall were $215 versus $1981 per practice and $17 versus $62 per child brought UTD. CONCLUSIONS: Population-based recall conducted centrally was more effective and cost-effective at increasing immunization rates in preschool children.

A framework for synthesizing intervention evidence from multiple sources into a single certainty of evidence rating: Methodological developments from a US National Academies of Sciences, Engineering, and Medicine Committee.

Despite research investment and a growing body of diverse evidence there has been no comprehensive review and grading of evidence for public health emergency preparedness and response practices comparable to those in medicine and other public health fields. The National Academies of Sciences, Engineering, and Medicine convened an ad hoc committee to develop and use methods for grading and synthesizing diverse types of evidence to create a single certainty of intervention-related evidence to support recommendations for Public Health Emergency Preparedness and Response Research. A 13-step consensus building method was used. Experts were first canvassed in public meetings, and a comprehensive review of existing methods was undertaken. Although aspects of existing review methodologies and evidence grading systems were relevant, none adequately covered all requirements for this specific context. Starting with a desire to synthesize diverse sources of evidence not usually included in systematic reviews and using GRADE for assessing certainty and confidence in quantitative and qualitative evidence as the foundation, we developed a mixed-methods synthesis review and grading methodology that drew on (and in some cases adapted) those elements of existing frameworks and methods that were most applicable. Four topics were selected as test cases. The process was operationalized with a suite of method-specific reviews of diverse evidence types for each topic. Further consensus building was undertaken through stakeholder engagement and feedback The NASEM committee's GRADE adaption for mixed-methods reviews will further evolve over time and has yet to be endorsed by the GRADE working group.

Community Guide Methods for Systematic Reviews of Economic Evidence.

INTRODUCTION: Community Guide systematic economic reviews provide information on the cost, economic benefit, cost-benefit, and cost-effectiveness of public health interventions recommended by the Community Preventive Services Task Force on the basis of evidence of effectiveness. The number and variety of economic evaluation studies in public health have grown substantially over time, contributing to methodologic challenges that required updates to the methods for Community Guide systematic economic reviews. This paper describes these updated methods. METHODS: The 9-step Community Guide economic review process includes prioritization of topic, creation of a coordination team, conceptualization of review, literature search, screening studies for inclusion, abstraction of studies, analysis of results, translation of evidence to Community Preventive Services Task Force economic findings, and dissemination of findings and evidence gaps. The methods applied in each of these steps are reported in this paper. RESULTS: Two published Community Guide reviews, tailored pharmacy-based interventions to improve adherence to medications for cardiovascular disease and permanent supportive housing with housing first to prevent homelessness, are used to illustrate the application of the updated methods. The Community Preventive Services Task Force reached a finding of cost-effectiveness for the first intervention and a finding of favorable cost-benefit for the second on the basis of results from the economic reviews. CONCLUSIONS: The updated Community Guide economic systematic review methods provide transparency and improve the reliability of estimates that are used to derive a Community Preventive Services Task Force economic finding. This may in turn augment the utility of Community Guide economic reviews for communities making decisions about allocating limited resources to effective programs.

Planned Out-of-Hospital Birth as a Risk Factor for Nonreceipt of Hepatitis B Immunization.

BACKGROUND: The hepatitis B vaccine (HBV) is recommended at birth to prevent perinatal hepatitis B transmission; however, many newborns still do not receive HBV. The extent to which planned out-of-hospital births, which have increased over the past decade, are associated with nonreceipt of the HBV birth dose is unknown. The purpose of this study was to determine whether a planned out-of-hospital birth location is associated with the nonreceipt of the HBV birth dose. METHODS: We performed a retrospective cohort study of all births from 2007 to 2019 recorded in the Colorado birth registry. χ2 analyses were used to compare maternal demographics by birth location. Univariate and multiple logistic regression were used to evaluate the association of birth location with nonreceipt of the HBV birth dose. RESULTS: In total 1.5% of neonates born in freestanding birth centers and 0.1% of neonates born at a planned home birth received HBV compared to 76.3% of neonates born in a hospital location. After adjusting for confounders, this translated to a large increase in the odds of not receiving HBV compared to in-hospital births [freestanding birth center (aodds ratio (aOR): 172.98, 95% confidence interval (CI): 136.98-219.88); planned home birth (aOR: 502.05, 95% CI: 363.04-694.29)]. Additionally, older maternal age, White/non-Hispanic race and ethnicity, higher income, and private or no insurance were associated with nonreceipt of the HBV birth dose. CONCLUSIONS: Planned out-of-hospital birth is a risk factor for nonreceipt of the HBV birth dose. As births in these locations become more common, targeted policies and education are warranted.

EDM forum supplement overview.

BACKGROUND: The Agency for Health Research and Quality funded the Electronic Data Methods Forum (EDM Forum) to share the experiences and learnings from 11 research teams funded through three different grant programs, each of which involve the use of electronic clinical data in Comparative Effectiveness Research and Patient-Centered Outcomes Research. OBJECTIVES: This overview is meant to describe the context in which the EDM forum was created and to introduce the set of papers in this supplement to Medical Care that describe the challenges and approaches to the use of electronic clinical data in the three key areas of analytic methods, clinical informatics and data governance. CONCLUSIONS: The participants in the EDM Forum are providing innovative approaches to generate information that can support the building of a "learning health care system." The compilation of papers presented in this supplement should serve as a resource to others working to develop the infrastructure for collecting, validating and using electronic data for research.

Reconsidering the criteria for evaluating proposed screening programs: reflections from 4 current and former members of the U.S. Preventive services task force.

In 1968, Wilson and Jungner published 10 "principles" for evaluating screening programs (Public Health Papers No. 34. Geneva, Switzerland: World Health Organization), criteria widely used since then. The 4 authors of this review (all current or former members of the U.S. Preventive Services Task Force) have found a different paradigm more useful for evaluating screening programs. This review was written independently of the USPSTF; the authors speak only for themselves and not for the USPSTF. They suggest evaluating screening programs not as a checklist but as a balance between the magnitude of benefits and the magnitude of harms, each estimated from a systematic review of the evidence. To emphasize a focus on health outcomes, the authors suggest reframing the target of screening as an umbrella concept: the "predictor of poor health." Evaluation groups should weigh health benefits and harms to estimate net benefits and then consider whether these net benefits justify the resources required. The final decision about implementation should be made by a democratic process that considers both the panel's evaluation of the evidence and nonevidence factors (e.g., resources available, other priorities, the informed population's preferences). The authors hope these suggestions stimulate further discussion about the optimal way to evaluate proposed screening programs.

Committee report: Method for evaluating conditions nominated for population-based screening of newborns and children.

The Secretary's Advisory Committee on Heritable Disorders in Newborns and Children is charged with evaluating conditions nominated for addition to the uniform screening panel and consequently making recommendations to the secretary of the US Department of Health and Human Services. This report describes the framework by which the committee approaches its task. Key decision nodes include initial review of every nomination to determine whether conditions are amenable for systematic evidence review, review of systematic evidence reviews conducted by the committee's external review group, and deliberation and formal recommendation for addition or exclusion to the uniform panel. Data analyzed include the accuracy and specificity of screening and diagnostic tests for nominated disorders, the extent of predicted health benefits, harms impact on disease course, and cost from early diagnosis and treatment. The committee process is guided by approaches used by similar entities, but more flexible criteria are sometimes needed to accommodate data limitations stemming from the rarity of many of these conditions. Possible outcomes of committee review range from recommendation to add a nominated condition to the uniform panel; provide feedback on specific gaps in evidence that must be addressed before making a decision; or rejection of a nomination (e.g., because of identified harms). The committee's structured evidence-based assessment of nominated conditions supports a consistently rigorous, iterative and transparent approach to its making recommendations regarding broad population-based screening programs for rare conditions in infants and children.