American College of Medical Genetics

Principles of Screening: Report of The Subcommittee on Screening of the American College of Medical Genetics Clinical Practice Committee

The screening program should have a clearly defined purpose.

• Distinctions must be made between carrier screening, screening for predisposition to disease, screening for presymptomatic disease, and screening for those affected with disease. The terms presymptomatic and symptomatic should be defined based on the nature and severity of specific symptoms. Certain phenotypic signs may have minimal clinical significance. The program should determine whether such signs will, or will not, result in classification of an individual as symptomatic.

• Newborn screening is a special case that, depending on the disorder and the screening method, may identify carriers, presymptomatic individuals, or affected neonates. Newborn screening represents an example of population-based screening as opposed to selective screening where a specified subset of the population is targeted.

• There should be a defined population for screening, e.g., newborns, a specific ethnic group for a disorder with increased frequency in that group, women at risk for breast cancer, etc.

• When a program is established, it must be clear whether the purpose is research or medical care. The decision to move a test from the research to the clinical arena must be carefully considered. The participant must be aware of benefits and risks of the information that will be forthcoming. If the screening is for research purposes, the subjects should be fully informed of the sources of financial support to minimize any perception of conflict of interest.

• Screening for clinical purposes preferably should be tied to the availability of intervention, including prenatal diagnosis, counseling, reproductive decision making, lifestyle changes, enhanced phenotype screening, etc.

• The introduction of the screening test is best accompanied by a public and professional education program.

• An essential component of a screening program is follow up evaluation and counseling by genetic professionals for participants with positive results in order to assure appropriate understanding and treatment, and to reduce anxiety and stigmatization. Counseling of individuals with negative results may, in some cases, be appropriate.

• All screening results are confidential. The results may only be revealed to the participant and/or the participant's personal physician. Research programs should apply for a certificate of confidentiality (Earley and Strong, 1995).

• In screening programs where there is less than 100% sensitivity, participants should be informed that a negative result does not necessarily rule out the possibility that they are carriers of, or affected with, the disorder tested. When there are a priori risks for the participants, the statistics should be accurately individualized for the particular patient.

• Due to potential problems of insurability and employability for carriers and/or affected individuals, participants may not want their insurance company or employer to know they are having the screening test performed. This may place the burden of payment for the screening test on the participant.

A screening program should be reviewed by the appropriate board.

• New screening programs should be considered by an appropriate review board, which will determine if consent is necessary.

• Review boards should determine, within the bounds of current federal regulations, if it is appropriate to involve fetuses, minor children, or incompetent adults in specific screening programs because of special risks and considerations, such as the implications for later onset diseases, self esteem, stigmatization, and altered family dynamics.

• Because of the sensitive nature of screening programs involving fetuses, minor children, and incompetent adults, review boards should weigh the risks and benefits to these groups separately from those of competent adults.

• Tests should be simple, accurate, and relatively inexpensive. They should identify most of the carriers and affected persons (high sensitivity) with few false positives (high specificity). Sensitivity, specificity and predictive value should be appropriate for the screening venue. Acceptable sensitivity and specificity will depend on the a priori risk of the screened population, and may vary for individuals within the population.

• The disorder for which screening is carried out should be of significant clinical severity. Severity will be viewed differently by individual patients.

• The correlation between phenotype and genotype should be understood for the targeted disease.

• Results of screening programs and the screening specimens themselves need to be maintained in a safe and secure environment.

REFERENCE

Members of the Subcommittee

Edward R.B. McCabe, M.D., Ph.D., Subcommittee Chair
UCLA School of Medicine

Corinne D. Boehm, M.S.
Johns Hopkins Hospital

George P. Henry, M.D.
Reproductive Genetics Center

Michelle M. LeBeau, Ph.D.
University of Chicago

Vicki M. Park, Ph.D.
University of Tennessee

Jerome I. Rotter, M.D.
Cedars-Sinai Medical Center

Margretta R. Seashore, M.D.
Yale University School of Medicine

This guideline is designed primarily as an educational resource for medical geneticists and other health care providers to help them provide quality medical genetic services. Adherence to this guideline does not necessarily assure a successful medical outcome. This guideline should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from this guideline.

Revised and approved by the ACMG Executive Committee on February 28, 1997.

©Copyrighted by the American College of Medical Genetics, 1997