Dear Dr. McCabe and Members of the Secretary's Advisory Committee on Genetic Testing:

The Association for Molecular Pathology (AMP) is a national medical specialty society representing physicians, doctoral scientists, and medical technologists who perform genetic testing as well as other tests based on molecular biology methods. AMP members practice their specialty in academic medical centers, community hospitals, independent clinical laboratories and federal and state health facilities.

On behalf of our membership, the Executive Council and Clinical Practice Committee of AMP have reviewed the SACGT document entitled "A Public Consultation on Oversight of Genetic Tests." In this communication, we would like to express our opinions on the issues and questions raised by the SACGT. Further, we are eager to explore how AMP might work in concert with the SACGT and other professional organizations to provide leadership and guidance toward a shared goal of appropriate, effective and ethical genetic testing.

In the following paragraphs, we have structured our responses by first reiterating each of the six Issues posed by the SACGT followed by our perspectives on each Issue.

Issue 1: What criteria should be used to assess the benefits and risks of genetic tests?

In many areas of medicine, genetic testing has become a standard of care due to its ability to provide vitally important diagnostic and prognostic information. We expect that advances in our understanding of the genetic basis of disease, coupled with information forthcoming from the Human Genome Project, will lead to a substantial increase in genetic testing. We also anticipate genetic testing will increasingly be used to guide selection of drug therapies in addition to its more conventional applications.

In this context, AMP holds that genetic testing is a medical service, and, as with other medical services, potential benefits must be balanced by considering the potential to cause medical, psychosocial and economic harm to the individual.

AMP supports the public expectation that genetic testing, like other diagnostic testing, meet the highest degree of quality control and quality assurance and reflect a patient's desire to obtain accurate information that will be confidentially handled and explained in an understandable manner.

AMP recognizes that genetic testing generates information pertinent to the patient (or proband) being tested and, by extension, to their family members. In some applications, genetic testing is most informative when both the patient and their family members are tested. While not unique to genetic testing, incorporation of family members requires that health care providers be equipped to explain the rationale for testing of family members other than the patient, and subsequently be able to explain the results of genetic testing to patients and their family members.

We hold that additional educational efforts and resources are needed within the health care profession to ensure appropriate counseling for patients and their family members undergoing genetic testing. Appropriate counseling needs to occur both before testing is performed to assure that patients make informed decisions about undergoing testing, as well as after testing to provide an explanation of test results.

Issue 2: How can the criteria for assessing the benefits and risks of genetic tests be used to differentiate categories of tests? What are the categories and what kind of mechanism could be used to assign tests to the different categories?

AMP appreciates the concept being considered by the SACGT that genetic tests be categorized based upon a combination of factors, "including test characteristics, availability of safe and effective treatments, and the social consequences of a diagnosis or identification of risk status." The challenge presented by this approach is that the development of a categorization system would have inherent arbitrary and perhaps in some cases, artificial, divisions.

We hold that a preferred alternative to categorization is to examine the role of individual genetic tests in the context of practice guidelines for the diagnosis and management of specific medical conditions. This approach offers an opportunity to assure that genetic tests are performed in an integral fashion with other medical services.

In addition to more immediate diagnostic applications, we anticipate an increase in genetic testing for predictive purposes. Increased resources for the pre- and post-analytical phases of genetic counselling by health care providers will be needed to manage the growth of predictive genetic testing.

Issue 3: What process should be used to collect, evaluate, and disseminate data on single tests or groups of tests in each category?

AMP holds that defining analytical and clinical validity, and clinical utility of genetic tests is essential and will require the design, execution and critical review of investigational studies that in some cases will need to be conducted over years to, perhaps, decade periods. We would further point out that the "validation" of the clinical utility of genetic tests is an evolutionary process that occurs over time beyond the proof of concept stage, as with other currently employed laboratory tests. Implementation and integration of genetic testing should not be unnecessarily delayed since for many disease states, genetic testing greatly improves diagnostic potential.

AMP holds that investigational studies will require the participation of individuals from multiple disciplines including molecular biology, biostatistics, population genetics and epidemiology. For many disorders in which genetic testing will be applied, multi-site investigational cooperatives will be needed to achieve recruitment of sufficient numbers of human subjects to allow meaningful statistical conclusions. AMP recommends greater support at the national level for such genetic epidemiology studies.

We recommend that dissemination of data on genetic tests occur through a variety of mechanisms that share a fundamental principle of peer review. This could include refereed publications, consensus statements, and practice guidelines.

AMP recommends the development of a national repository of data and resources for information on specific genetic tests that would be available to health care providers.

We recognize the growing interest of the public for information on genetic tests. Increasingly, the public is seeking medical information via Internet resources. We support the concept of developing peer reviewed Internet resources that provide information on genetic tests for health care providers and the public.

Issue 4: What are the options for oversight of genetic tests and the advantages and disadvantages of each option?

AMP holds that oversight of genetic tests be uniformly applied to all laboratories performing genetic testing whether they are based in the academic or private sectors.

We hold that the guidelines enunciated in the Clinical Laboratory Improvement Amendments (CLIA) and those of the College of American Pathologists (CAP) and the American College of Medical Genetics (ACMG) provide a productive framework for continuous improvement in the quality of genetic testing. AMP supports continued oversight by these mechanisms.

We hold that participation in proficiency testing programs such as those administered jointly by the CAP and the ACMG provide the critical feedback that fosters improved laboratory performance. AMP supports the continuation and expansion of these programs with the goal of building upon their strengths.

Issue 5: What is an appropriate level of oversight for each category of genetic test?

As discussed earlier under Issue 2, AMP holds that a preferred alternative to categorization is to examine the role of individual genetic tests in the context of practice guidelines for the diagnosis and management of specific medical conditions, without distinguishing genetic tests based on other criteria.

Issue 6: Are there other issues in genetic testing of concern to the public?

AMP holds that the process of genetic testing should begin with a dialogue between the patient and their health care provider. This dialogue should incorporate the rationale for the recommended genetic test and include the principles of informed consent. Subsequently, the results of genetic testing should be related to the patient by the health care provider, with discussion of the medical and social implications of the results for the patients as well as other family members. In this process, every effort should be made to maintain appropriate confidentiality.

AMP holds that the current practice of gene patenting and exclusive test licensing resulting from gene patenting prevents optimum access to genetic testing for all patients. AMP holds that these current practices need to be re-examined at the national level.

Thank you for this opportunity to provide comments on genetics testing to the SACGT.

Sincerely,

Debra G.B. Leonard, MD, PhD
President

Karl V. Voelkerding, MD
President-elect

Wayne W. Grody, MD, PhD
Chair, Clinical Practice Committee

Appendices

1. Molecular Pathology. The College of American Pathologists Molecular Pathology Checklist.
   
    
2. Association for Molecular Pathology. AMP Statement: Recommendations for In-House Development and Operations of Molecular Diagnostic Tests. Am J Clin Path 1999; 111:449-463
   
    
3. Association for Molecular Pathology. Special Report: Goals and Objectives for Molecular Pathology Education in Residency Programs. J Mol Diag 1999; 1:5-15
   
    
4. Certification of Subspecialization in Molecular Genetic Pathology. Sponsored by The American Board of Medical Genetics and The American Board of Pathology. Approved by ABMS, March 18, 1999
   
    
5. AMP Position on Patenting of Genetic Tests. November 22, 1999