Topic Areas and Sample Questions Addressed in an Evidence-Based Review

The evidence-based review for each condition has a set of Key Questions about the condition, incidence and prevalence, natural history, screening, treatment, and the public health impact.

The Evidence-Based Review Group (ERG) explores eight topic areas during an evidence-based review. The specific questions within each topic area are adapted for each condition under review. Examples of the types of questions which might be addressed within each topic area are as follows.

Epidemiology with Clinical Detection and Usual Care

This topic reviews data about how many people have the condition; when symptoms appear; and the condition’s typical course without newborn screening.

Key Questions under this topic include:

  • What is the case definition of the condition?
  • How many new cases of the condition are there in the U.S. each year?
  • How common are carriers of the condition?
  • How common are different forms of the condition? Does the condition’s course differ for each form?
  • How common are changes in condition-related genes that do not cause the condition?

Screening

This topic reviews the screening process. It covers details of the screening process, how well it works, and whether screening predicts the condition’s form or severity.

Key Questions under this topic include:

  • What is the screening process for the condition? What samples does it use?
  • How well does screening find the marker it is designed to find?
  • How well does screening find children with the condition?
  • If screening finds a newborn at high risk for the condition, how likely is the child to have the condition?
  • Can screening predict the condition’s form and severity? Can screening tell the condition apart from related conditions?
  • Do methods to confirm the quality of screening exist?
  • Do data on the likely outcomes of screening exist?

Short-Term Follow-Up and Diagnosis

This topic reviews data on short-term follow-up of newborns at high risk for the condition. It covers whether testing to confirm a diagnosis is available, accessible, and feasible.

Key Questions under this topic include:

  • How is the condition diagnosed in newborns?
  • Can diagnosis tell severe/early-onset forms and less severe/later-onset forms apart?
  • Do methods to confirm the quality of diagnosis exist?
  • For diagnoses that involve genetic testing, what is known about gene changes related to the condition and how these changes affect symptoms? Is an exam needed to confirm diagnosis?
  • How long does it take to get a diagnosis?
  • What other factors that affect treatment are important during short-term follow-up?

Benefits and Harms of Screening and Diagnosis (Not Related to Treatment)

This topic reviews benefits and harms, not related to treatment, that could result from newborn screening and early diagnosis. Many benefits and harms affect both the newborn and family.

Key Questions under this topic include:

  • What are the harms of wrongly classifying a baby without the condition as high-risk?
  • What are the harms of wrongly classifying a baby with the condition as low-risk?
  • What are the harms/benefits of diagnosing newborns who do not have the condition with condition-related gene changes?
  • What are the harms/benefits of diagnosing newborns found from newborn screening with the condition?

Treatment and Long-Term Follow-Up Care

This topic reviews current treatment practices and guidelines. It covers treatment types, details, and duration and whether treatment changes based on age or symptoms.

Key Questions under this topic include:

  • What are the treatment indications for the condition?
  • Do treatment and long-term follow-up guidelines exist?
  • Are there recommended treatments for the condition?
  • Are there clinical experts who can oversee treatment and long-term follow-up care?

Outcomes of Early Detection and Treatment

Primary Health Outcomes

This topic reviews the condition’s primary health outcomes (e.g., survival, age of mortality). It may also cover how other measures relate to these outcomes.

Key Questions under this topic include:

  • What are the key primary health outcomes related to treatment for the condition?
  • Do outcomes differ for newborns identified with or without newborn screening?
  • Other than age at treatment onset, what factors influence treatment’s effect on these outcomes?

Secondary Health Outcomes

This topic reviews other health outcomes related to the condition.

Key Questions under this topic include:

  • What are the key secondary outcomes related to treatment of the condition?
  • Do outcomes differ for newborns identified with or without newborn screening?
  • Other than age at treatment onset, what factors influence treatment’s effect on these outcomes?

Intermediate Outcome Measures

This topic considers whether and how much treatment and long-term follow-up affect other measures.

Key Questions under this topic include:

  • What other measures can help to monitor the condition and inform treatment decisions?
  • How strongly do these measures relate to the condition’s primary outcomes?
  • For babies found with versus without newborn screening, does treatment affect these other measures?
  • Does treatment timing improve outcomes?
  • Other than age at treatment onset, what factors influence treatment’s effect on these measures?

Benefits and Harms of Treatment and Long-Term Follow-Up

This topic reviews the benefits and harms of treatment and long-term follow-up care for newborns found with versus without newborn screening.

Key Questions under this topic include:

  • For babies found with versus without newborn screening, does treatment for the condition improve or worsen any health outcomes?
  • For babies found with newborn screening, do improved outcomes lead to other outcomes that could be harmful?
  • For babies found with versus without newborn screening, is it possible to improve benefits or decrease harm?

Public Health Impact

This topic reviews the impact of adding newborn screening for the condition on population health and the public health system.

Population Health

This topic covers the impact of newborn screening on the population by predicting how many babies would be found and treated with versus without newborn screening.

Key Questions under this topic include:

  • What is the impact of screening on all U.S. newborns?
  • What is the impact of screening on the condition’s incidence/prevalence?
  • What is the impact of screening on treatment outcomes?

Public Health System Impact

This topic covers the resources, feasibility, and readiness of state newborn screening programs to begin screening for the condition and the costs to start screening.

Key Questions under this topic include:

  • What resources do public health and health care systems need to offer screening and short- and long-term follow-up services for the condition?
  • How feasible is it to begin screening all U.S. newborns for the condition?
  • How ready are state programs to screen newborns for the condition?
  • What are the estimated costs of screening projected to impact the public health system?
Date Last Reviewed:  January 2022