Draft Genetic Test Review

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Cystic Fibrosis
Clinical Utility

(347KB)

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CLINICAL UTILITY

Question 26: What is the natural history of the disorder?
Question 27: What is the impact of a positive (or negative) test on patient care?
Question 28: If applicable, are diagnostic tests available?
Question 29: Is there an effective remedy or acceptable action, or other measurable benefit?
Question 30: Is there general access to that remedy or action?
Question 31: Is the test being offered to a socially vulnerable population?
Question 32: What quality assurance measures are in place?
Question 33: What are the results of pilot trials?
Question 34: What health risks can be identified for follow-up testing and/or intervention?
Question 35: What are the financial costs associated with testing?
Question 36: What are the economic benefits associated with actions resulting from testing?
Question 37: What facilities/personnel are available or easily put in place?
Question 38: What educational materials have been developed and validated, and which of these are available?
Question 39: Are there informed consent requirements?
Question 40: What methods exist for long term monitoring?
Question 41: What guidelines have been developed for evaluating program performance?

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CLINICAL UTILITY

Question 37: What facilities are necessary for prenatal screening for cystic fibrosis?

Summary Facilities are necessary for three phases of screening activities and need to be centrally administered as a comprehensive program. The three phases include Pre-analytic activities occur at the primary care sites and include education, consent, and sample management Analytic activities occur at the laboratory and include sample processing, testing and reporting. A minimum of 60 laboratories are likely to be needed to manage 1,000,000 couples tested annually. Between 100 and 500 new DNA clinical technologists in the United States will need to be available. Post-analytic activities occur at clinical referral sites and can include counseling of carrier individuals as well as couples where both partners have positive test results. Only 3 full time counselor equivalents would be needed to provide services to couples where both are carriers (assuming 1,000,000 couples tested annually). Between 50 and 100 additional full time counselor equivalents would be needed if all carrier individuals identified are also provided services. Facilities for managing prenatal cystic fibrosis screening can be developed in the same manner as existing prenatal screening programs and may be superimposed upon existing infrastructure.

In order for a prenatal screening program to be properly implemented, appropriate facilities (e.g., laboratory space, equipment, and computers) and staff are required. Prenatal screening for cystic fibrosis needs to be viewed in the context of a combined laboratory and patient service program. That is, a centralized administrative function oversees all aspects of the screening program. This includes educational materials and consent, laboratory testing and interpretation, and finally, genetic counseling and diagnostic testing. Existing prenatal screening models indicate that the Laboratory Directors is likely to be responsible for program administration, along with other genetics professionals. Screening activities can be divided into three phases, and the facilities and personnel for each of these phases is discussed below.

Pre-analytic activities

These activities performed at the primary care sites and include physician and patient education, obtaining consent, obtaining an appropriate sample, completing the requisition slip, and ensuring that the sample reaches the testing laboratory. The program needs to ensure that primary care providers have the necessary information by providing physician educational materials, in-service training, and face-to-face meetings. Patient educational materials also need to be made available (the content and type of materials are covered in more detail in Questions 39 and 40). A program staff member should be available to answer questions by phone. Sample collection materials should be clearly specified or provided. A simple and clear test requisition slip for screening should be provided (Question 34). Based on results from pilot trials, primary care providers should be informed that, on average, 5 to 10 minutes of time should be allocated per patient for educational/consent activities.

Analytic activities

The laboratory facilities and resources that are needed can be estimated from published information concerning prenatal screening for Down syndrome and open neural tube defects. There are approximately 4 million pregnant women per year in the United States, and prenatal serum screening for Down syndrome and neural tube defects is chosen by over half (Palomaki et al., 1997). That testing is performed in about 200 laboratories. Within a few years of cystic fibrosis prenatal screening being made a standard of care, as many as 1 million pregnancies might be screened annually. How many laboratories might be expected to perform such screening, and what might their characteristics be? Molecular testing for cystic fibrosis is highly complex and requires expert interpretation. This limits the number of laboratories capable of delivering this service. Existing laboratories that offer cystic fibrosis testing include for-profit laboratories, not-for-profit laboratories and academic institutions. Some states may choose to oversee and manage such testing (as is the case in California for second trimester maternal serum screening for Down syndrome and open neural tube defects). According to the latest American College of Medical Genetics/College of American Pathologists' External Proficiency Testing Program, 36 laboratories now offer cystic fibrosis testing. However, some of these may not pursue mass screening. If 30 laboratories were to provide services to 1 million pregnancies, they would test an average of over 30,000 couples per year. This would currently be difficult, given the limited level of automation available (high-throughput automated systems are not readily available). Realistically, the number of qualified laboratories would need to at least double and could expand to as many as 150. Assuming that one laboratory technician can log-in, process, test and report 2,000 samples per year, an estimated 500 new DNA clinical technologists would be required. Were automated systems available, this number might be reduced considerably, to perhaps 100 to 200 technologists. The number of new technologists may be further reduced if some were currently underutilized or engaged in research.

Post-analytic activities

Post-analytic activities center around the counseling of screen positive individuals (two-step or expanded one-step models only) or screen positive couples (all models). Screen positive couples are usually offered a comprehensive genetic counseling session estimated to take between one-half and one hour. Only about 1:850 couples will require this level of counseling (this rate is for the non-Hispanic Caucasian and Jewish populations; screen positive couples occur less frequently in other racial/ethnic groups – Question 20). In a hypothetical population of 1,000,000 couples screened, the one hour per couple counseling time is equivalent to about 2 or 3 full-time genetic counselors. Were programs to utilize the two-step approach and offer a one-half hour genetic counseling session to all screen positive women (about 1 in 30), the genetic counselor time would be much higher, equivalent to 45 or 50 full-time genetic counselors. Were a half-hour counseling session to be offered to all screen positive individuals in an expanded one-step program (about 1 in 15), the genetic counselor time would total nearly 100 full-time genetic counselors. To put these numbers in perspective, between 90 and 100 genetic counselors graduate from training programs each year. At most, 340 fetuses affected with cystic fibrosis would be identified among the 1,000,000 couples tested, and couples in this situation would need another level of counseling and support to help them reach a course of action which would be most appropriate for them.

Will adequate facilities be available for prenatal cystic fibrosis screening?

Some information concerning the answer to this question can be found in the history of prenatal screening for open neural tube defects, beginning in the late 1970's and early 1980's. At that time, successful pilot trials had been reported from both the United Kingdom and the United States, but wide implementation in the United States was considered to be difficult, due the variety of health delivery mechanisms. A few qualified laboratories began offering testing, and their success encouraged others to begin. With the statement from the American College of Obstetricians and Gynecologists in 1985 suggesting that such testing should become routine, resources were found to train, implement and oversee widespread screening for neural tube defects in the United States. A similar path is likely to be followed now that the policy recommendations from the Joint Committee on Prenatal Cystic Fibrosis Testing (American College of Medical Genetics/American College of Obstetricians and Gynecologists) have been issued (Grody et al., 2001). One factor that makes the introduction of prenatal screening for cystic fibrosis less demanding is that mechanisms are already in place for widespread delivery of other prenatal screening services. In many instances, the new screening protocols can be superimposed on existing infrastructure.

References

Palomaki GE, Knight GJ, McCarthy JE, Haddow JE, Donhowe JM. 1997. Maternal serum screening for Down syndrome in the United States: A 1995 survey. Am J Obstet Gynecol 16:1046-1051.

American College of Obstetricians and Gynecologists. The best possible defense position. ACOG Department of Professional Liability, May 1985

Grody WW, Cutting GR, Klinger KW, Richards CS, Watson MS, Desnick RJ. 2001. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med 3:149-154.