Genomics|Family History|Tables|Chronic Diseases

Research Priorities for Evaluating Family History in the Prevention of Common Chronic Diseases
Paula W. Yoon ScD, MPH, Maren T. Scheuner MD, MPH and Muin J. Khoury MD, PhD

Tables

TABLE 1: Elements and key components of evaluation framework for family history as screening tool

Elements	Definition	Components
Analytic validity	An indicator of how well a test or tool measures the property or characteristic (disease status among relatives) that it is intended to measure	Analytical sensitivity Analytical specificity
Clinical validity	A measurement of the accuracy with which a test or tool identifies or predicts a clinical condition	Clinical sensitivity Clinical specificity Positive predictive value Negative predictive value
Clinical utility	Degree to which benefits are provided by positive and negative test results (presence and absence of family history for disease)	Availability of effective interventions Health risks and benefits Economic assessment
Ethical, legal, and social implications	Issues affecting data collection and interpretation that might negatively impact individuals, families, and society	Stigmatization Discrimination Psychological harm Risks to privacy and confidentiality

TABLE 2: Criteria for selecting diseases to include in family history tool

● Substantial public health burden

● Well-defined case definition

● Awareness of disease among relatives

● Accurately reported by family members

● Family history is established risk factor

● Effective interventions for primary and secondary prevention

TABLE 3: Specific questions for assessing the validity and utility of family history information for disease prevention^a

Element	Specific questions
Analytic validity	What is the sensitivity and specificity for reporting each disease included in the tool and how does the sensitivity and specificity vary by:
	1) Type of relative (e.g., parents, siblings, children, grandparents, aunts and uncles)
	2) Proband characteristics (e.g., age, gender, race/ethnicity, socioeconomic status, and disease status)
	3) Disease characteristics (e.g., prevalence, morbidity, mortality, diagnostic criteria, and social acceptability)
	4) Disease terminology (e.g., heart disease vs coronary artery disease)
	5) Phrasing of the question (e.g., “Have you ever had. . .” vs “Has a doctor ever told you that you had. . .”)
	How accurate is age of onset information?
	What settings yield more valid information?
	What formats yield more valid information?
	What gold standards exist to validate the reported data?
Clinical validity	Does the clinical validity improve if age of diagnosis is known?
	Does information about distant relatives (second- and third-degree) improve clinical validity?
	What is the relative risk associated with each disease for each strata of the family history risk classification scheme (i.e., high, moderate, and average)?
	What is the prevalence of the disease in each population to be screened?
	What is the probability that a person will develop disease given a positive or negative family history?
	How valid is the risk classification system for predicting disease?
	What classification system for family history risk results in the highest predictive value?
	Has the tool been adequately validated in populations to which it may be offered?
	How often should family history information be updated?
	What are the factors (e.g., genetic, environmental, and behavioral) that modify the relationship between familial risk and disease occurrence?
Clinical utility	What is the natural history of the disease (may determine when family history should first be ascertained)?
	Are there effective interventions for primary and/or secondary prevention?
	Is there general access to the interventions?
	What strategies could be adopted to improve compliance with recommended interventions?
	Are educational materials available to explain familial risk and the recommended interventions?
	What is the short-term and long-term impact of a positive or negative family history on screening and disease prevention?
	Are there any health risks associated with the family history assessment and subsequent interventions?
	What are the financial costs associated with the family history assessment?
	What are the economic benefits associated with interventions resulting from the assessment?
	What methods exist for evaluating and monitoring the family history assessment process and its benefits and risks?
Ethical, legal, & social implications	Are there legal issues regarding informed consent, ownership of the data, obligation to disclose, or reporting requirements?
	What is known about stigmatization, discrimination, privacy/confidentiality, and personal/family and social issues associated with family history assessment and risk labeling?
	What safeguards have been described to protect privacy and are these safeguards in place and effective?

^aAdapted from a model process developed by the Foundation for Blood Research36 for evaluating genetic tests.