Role of Professional, Laboratory, and Patient Guidelines and Best Practices: the Cystic Fibrosis Guidelines Testing Story

Publication Details

The genetic test for cystic fibrosis (CF) carrier screening is well-established. In 2001, the American College of Obstetricians and Gynecologists (ACOG) released test guidelines for physicians, and the American College of Medical Genetics (ACMG) released guidelines for laboratories. The impact of these guidelines has been followed and evaluated. Newer genetic tests can incorporate the lessons learned and apply them to future guidelines.

The presenters were (1) Deborah Driscoll, MD, Professor and Chair, Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, (2) Kathy Hudson, PhD, Director, Genetics and Public Policy Center (GPPC), and (3) Jeffrey A. Kant, MD, PhD, Professor, Pathology and Human Genetics and Director, Division of Molecular Diagnostics, University of Pittsburgh Medical Center.

The CFTR gene (the gene associated with cystic fibrosis) and its common mutations were identified in 1989. In 1997, the NIH held a Consensus Development Conference and called for population-based screening for CF. As noted above, clinical and laboratory guidelines for carrier screening were released in 2001. Two years after the guidelines were released, a survey was conducted to evaluate implementation by physicians [note 3], as a result of a number of concerns about issues such as provider’s interpretation of test results and the adequacy of both pre-test and post-test counseling.

According to Driscoll, the goals of CF carrier screening are to identify couples at risk for having children with classic CF and to allow couples to make informed reproductive decisions.

The purpose of the guidelines was to:

  • educate physicians about CF
  • provide a model for implementing CF carrier screening into routine practice
  • provide materials to assist with implementation (such as consent forms and patient education brochures)
  • provide recommendations for who should be offered CF carrier screening

The survey focused on two questions:

  • How familiar are obstetricians and gynecologists with CF carrier screening guidelines?
  • Do the guidelines impact their practice behavior?

The survey concluded that doctors were doing a good job with their pregnant patients, but there was substantial room for improvement with the non-pregnant patients. Driscoll explained that patients find it difficult to get reimbursement for preconception carrier screening.

Driscoll discussed the lessons that have been learned through the CF carrier screening program. In summary:

  • Guidelines have a significant impact on practice behavior.
  • Guidelines are an important source of information to providers.
  • It is important to keep guidelines simple. Doctors want to be told what to do.
  • Providers need continuing medical education in order to increase their comfort level with the results and to help them better counsel their patients.
  • By educating the public, the public will become more proactive in its requests for testing.
  • Alternative venues for reaching providers are needed.

Hudson then addressed laboratory compliance with the guidelines. From December 2005 to March 2006 an array of data was collected by GPPCabout CF carrier screening clinical lab practices and the opinions and attitudes of the lab directors.

According to Hudson, the current ACMG guidelines state that:

  • Labs should routinely screen for only 23 mutations.
  • 5T had been tested only as a reflex to a finding of R117H, since R117H has a complex association with the 5T/7T/9Tvariants.
  • It might be appropriate to test additional alleles, depending upon the race and ethnicity of the population being tested.

The initial guidelines are now six years old. The GPPCsurvey asked: How are the labs doing?

It was found that only 10% of labs are in compliance with the recommended 23 mutation screening panel. The other 90% test more than 23 mutations. Labs are doing a better job complying with the 5T reflex recommendation, with seventy-five percent performing the test in accordance with the guidelines. However, overall, only 7% of labs are in compliance with both recommendations. Thirteen percent of labs are in compliance with neither guideline.

Why are the compliance rates so low on the mutation screening panel recommendation? Hudson proposed some questions, which, when answered, might explain the statistics:

  • Are the guidelines not useful? Are they out of date?
  • Are providers and patients demanding that more than 23 mutations be tested?
  • Are expanded panels being used to accommodate the racial and ethnic diversity of the population being tested?
  • Are the available testing platforms driving the number of mutations that are being screened?

Beginning with the belief that compliance with guidelines improves outcomes —and perhaps more research is needed to confirm that belief—how can better compliance with existing guidelines be encouraged? Hudson offered some ideas for consideration:

  • Would linking compliance to reimbursement be useful?
  • Should compliance be linked to oversight?
  • Would embedded, electronic medical records be helpful?
  • Are concerns about liability driving lack of compliance?
  • Do better decision making tools need to be developed?

Kant also provided insight into the CF laboratory screening guidelines and current issues surrounding the test. One of the most important items the lab generates is the report. The report is for both the clinician and the patient; in fact, many patients ask for their report. Kant described the type of report that his lab provides, which consists of two sections: interpretation and results.

The interpretive section contains the essence of the information. For a negative result, the report might say “no mutations identified using a recommended screening panel.” For a positive result, the report would name the discovered mutation and recommend testing of the patient’s partner and relatives.

In the results section, the report gives a brief description of the disease. It emphasizes that carrier rates vary by ethnicity and that a negative result retains a residual carrier risk. The lab report provides details about the residual risk.

He explained the logistics of CF testing. Many times the patient has received a prescription for the test and has a blood sample drawn at a local draw station. It is not always possible for the lab to know the reason for the test—is it carrier testing or is the patient symptomatic? The screening panel is not optimal for diagnostic testing, but it is a useful starting point.

The providing physician obtains the formal consent form. Genetic testing is a process, and consent is only one part of the process. Labs take great care to convey information in a report that is both accurate and useful, but it is not uncommon for results to be provided over the phone with little detail. There needs to be adequate post-test review with negative-result patients in order to convey residual carrier risk. Positive-result patients should receive formal genetic counseling. Sometimes, the implications for relatives are not discussed in detail. Kant commented that “what the patients actually take away from the laboratory test” varies greatly.

Physicians and patients want their results as quickly as possible, which places financial pressures on labs. Labs are often presented with questions about reimbursement, but this information is not readily available to them. Labs do supply CPT coding, and the codes often confuse the payers.