Table 1.

Comparison of evaluative frameworks: Dobrow’s consolidated screening principles [21••], Public Health England Screening evaluation criteria [23] and ACCE framework for review of genetic testing [24]

Domain	Dobrow screening principles		Public Health England Criteria	ACCE framework questions
Condition	Epidemiology	“The epidemiology of the disease or condition should be adequately understood, and the disease or condition should be an important health problem”	“Condition should be an important health problem […]. Epidemiology, incidence, prevalence […] of the condition should be understood…”	“What is the specific clinical disorder to be studied?” “What is the prevalence of the disorder in this setting?”
	Natural history	“The natural history of the disease or condition should be adequately understood […] and there should be a clear pre-clinical phase”	“Natural history of the condition should be understood” “If the carriers of a mutation are identified as a result of screening the natural history of people with this status should be understood, including the psychological implications”	“What are the clinical findings defining this disorder?” “What is the natural history of the disorder?”
	Target population	“The target population for screening should be clearly defined (e.g. with an appropriate target age range), identifiable and able to be reached”	Target population not explicitly considered, though referenced in test domain	Target population not explicitly considered
		Other primary prevention measures not explicitly considered	“Cost-effective primary prevention interventions should have been implemented as far as practicable”	Other primary prevention measures explicitly not considered
Test	Test performance	“Screening test performance should be appropriate for the purpose, with all key components specific to the test (rather than the screening program) being accurate (e.g. in terms of sensitivity, specificity and positive predictive value) and reliable or reproducible. The test should be acceptable to the target population and it should be possible to perform or administer it safely, affordably and efficiently.”	“There should be a simple, safe, precise and validated screening test” “The test, from sample collection to delivery of results, should be acceptable to the target population”	“What DNA test(s) are associated with this disorder?” “Are preliminary screening questions employed?” “Is it a stand-alone test or is it one of a series of tests? If it is part of a series… are all tests performed in all instances (parallel) or are only some tests performed on the basis of other results (series)?” “Is the test qualitative or quantitative?” “How often is the test positive when a mutation is present (sensitivity)?” “How often is the test negative when a mutation is not present (specificity)?” “Is an internal QC program defined and externally monitored?” “Have repeated measurements been made on specimens?” “What is the within- and between-laboratory precision?” “If appropriate, how is confirmatory testing performed to resolve false positive results in a timely manner?” “What range of patient specimens have been tested?” “How often does the test fail to give a useable result?” “How similar are results obtained in multiple laboratories using the same, or different technology”
	Test interpretation	“Screening test results should be clearly interpretable and determinate (e.g. with known distribution of test values and well-defined and agreed cut-off points) to allow identification of the screening participants who should (and should not) be offered diagnostic testing and other postscreening care”	“The distribution of test values in the target population should be known and a suitable cut-off level defined and agreed”	“How often is the test positive when the disorder is present (sensitivity)?” “How often is the test negative when a disorder is not present (specificity)?” “Are there methods to resolve clinical false positive results in a timely manner?” “Has the test been adequately validated on all populations to which it may be offered?” “What are the positive and negative predictive values?” “What are the genotype/phenotype relationships?” “What are the genetic, environmental or other modifiers?”
		Genetic testing/reviewing of variants not explicitly considered	“If the test is for a particular mutation or set of genetic variants the method for their selection and the means through which these will be kept under review in the programme should be clearly set out”	Review of genetic variants not explicitly considered
Intervention	Postscreening options	“There should be an agreed on course of action for screening participants with positive screening test results that involves diagnostic testing, treatment or intervention, and follow-up care that will modify the natural history and clinical pathway for the disease or condition that is available, accessible and acceptable to those affected; and that results in improved outcomes …”	“There should be an agreed policy on the further diagnostic investigation of individuals with a positive test result and on the choices available to those individuals” “There should be an effective intervention, with evidence that intervention at presymptomatic stage leads to better outcomes” “There should be agreed evidence based policies covering which individuals should be offered interventions” “Clinical management of the condition and patient outcomes should be optimised in all health care providers prior to participation in a screening programme”	“What is the impact of a positive (or negative) test on patient care?” “If applicable, are diagnostic tests available?” “Is there an effective remedy, acceptable action, or other measurable benefit? Is there general access to that remedy or action?” “What are the results of pilot trials?” “What health risks can be identified for follow-up testing and/or intervention?”
Programme	Infrastructure	“There should be adequate existing infrastructure […] or a clear plan to develop adequate infrastructure, that is appropriate to the setting to allow for timely access to all components of the screening program”	“Adequate staffing and facilities […] should be available prior to the commencement of the screening programme”	“What is the clinical setting in which the test is to be performed?” “What facilities/personnel are available or easily put in place?”
	Coordination	“All components of the screening program should be coordinated and, where possible, integrated with the broader health care system…”	“There should be a plan for managing and monitoring the screening programme”	“What methods exist for long term monitoring?”
	Acceptability and ethics	“All components of the screening program should be clinically, socially and ethically acceptable to screening participants, health professionals and society, and there should be effective methods for providing screening participants with informed choice, promoting their autonomy and protecting their rights.”	“Evidence the complete screening programme is clinically, socially and ethically acceptable to health professionals and the public” “Evidence-based information […] should be made available to potential participants to assist them in making an informed choice” “Public pressure for widening the eligibility criteria, for reducing the screening interval, and for increasing the sensitivity of the testing process, should be anticipated. Decisions […] should be scientifically justifiable to the public”	“Is the test being offered to a socially vulnerable population?” “What educational materials have been developed and validated and which of these are available?” “Are there informed consent requirements?” “What is known about stigmatisation, discrimination, privacy/confidentiality and personal/family social issues?” “Are there legal issues regarding consent, ownership of data and/or samples, patents, licencing, proprietary testing, obligation to disclose, or reporting requirements?” “What safeguards have been described and are these safeguards in place and effective?”
	Benefits and harms	The expected range and magnitude of benefits […] and harms […] for screening participants and society should be clearly defined and acceptable, and supported by existing high-quality scientific evidence (or addressed by ongoing studies) that indicates that the overall benefit of the screening program”	“There should be evidence from high quality randomised controlled trials that programme reduces morbidity and mortality” “The benefit gained by individuals should outweigh harms”	“Is there an effective remedy, acceptable action, or other measurable benefit? Is there general access to that remedy or action?”
	Economic evaluation	“An economic evaluation […] of the screening program, using a health system or societal perspective, should be conducted (or a clear plan to conduct an economic evaluation) to assess the full costs and effects of implementing, operating and sustaining the screening program while clearly considering the opportunity costs and effect of allocating resources to other potential nonscreening alternatives”.	“The opportunity cost of the screening programme […] should be economically balanced in relation to healthcare expenditure as a whole” “All other options for managing the condition should have been considered (such as improving treatment or providing other services), to ensure that no more cost effective intervention”	“What are the financial costs associated with testing?” “What are the economic benefits associated with actions resulting from testing?”
	Quality and performance	“The screening programme should have clear goals or objectives that are explicitly linked to program planning, monitoring, evaluating and reporting activities, with dedicated information systems and funding, to ensure ongoing quality control and achievement of performance targets”	“There should be a plan for managing and monitoring the screening programme and an agreed set of quality assurance standards”	“What quality assurance measures are in place?” “What guidelines have been developed for evaluating program performance?”