Population screening for genetic disorders in the 21st century: evidence, economics, and ethics

Proposals for population screening for genetic diseases require careful scrutiny by decision makers because of the potential for harms and the need to demonstrate benefits commensurate with the opportunity cost of resources expended.

We review current evidence-based processes used in the United States, the United Kingdom, and the Netherlands to assess genetic screening programs, including newborn screening programs, carrier screening, and organized cascade testing of relatives of patients with genetic syndromes. In particular, we address critical evidentiary, economic, and ethical issues that arise in the appraisal of screening tests offered to the population. Specific case studies include newborn screening for congenital adrenal hyperplasia and cystic fibrosis and adult screening for hereditary hemochromatosis.

Organizations and countries often reach different conclusions about the suitability of screening tests for implementation on a population basis. Deciding when and how to introduce pilot screening programs is challenging. In certain cases, e.g., hereditary hemochromatosis, a consensus does not support general screening although cascade screening may be cost-effective.

Genetic screening policies have often been determined by technological capability, advocacy, and medical opinion rather than through a rigorous evidence-based review process. Decision making should take into account principles of ethics and opportunity costs.