been fully determined. If the manufacturer is to contact physicians directly, testees must be informed if the manufacturer will have their names. Once provisional premarket approval is granted, manufacturers should be allowed to charge a market price for the test. This process may require new legislation.
Provisional premarket approval, with periodic postmarket study for which the sponsor would be responsible, could also be used to cover the development of tests for rare conditions (which is the intent of the humanitarian device exemption). The committee therefore recommends that Congress consider the need for legislation in the spirit of the Orphan Drug Act that would give manufacturers the incentive to develop diagnostic medical devices for genetic tests of limited marketability.
The appearance of clinical disease is the only possible confirmation of many genetic tests, and that may not occur until many years after testing. Investigators should be permitted to convey the results of investigational tests to subjects who are aware of the investigational nature of the test. Thus, clinical decisions could be made on the basis of the results as long as the investigator has an approved investigational device exemption. FDA should make it clear that in such cases, with an approved IDE, results could be communicated to the patient or to his or her physician so that interventions can be instituted accordingly.
Since many IRBs are not experienced in the review of investigational genetic testing protocols, the committee recommends that the National Institutes of Health (NIH) Office for Protection from Research Risks (OPRR) and the National Center for Human Genome Research Ethical, Legal, and Social Implications (ELSI) Program coordinate efforts to assist IRBs in coping with this responsibility, and ELSI should consider supporting efforts to assist IRBs in this task. Other federal agencies (such as the FDA) and professional groups should also consider developing guidelines to help IRBs cope with this added responsibility (such as the informed consent guidelines for research involving genetic testing developed by the Alliance of Genetic Support Groups and the ASHG). The formation of a national advisory body on genetic testing could also be helpful in educating IRBs concerning research involving genetic testing (see Chapter 9). IRBs used by commercial organizations should also have a broad, unbiased membership.
Compliance with FDA requirements for premarket approval and approved investigational device exemption is essential to ensuring safe and effective use of a genetic test, just as compliance with CLIA88 is essential for any laboratory performing genetic tests for clinical purposes. The committee recommends that the FDA publicize widely to potential sponsors, including academic centers, that DNA probes and other reagents essential to the performance of genetic tests are medical devices. Consequently, whenever they are used for clinical purposes, genetic test devices (i.e., test kits, reagents, probes, etc.) either must be labeled "for investigational use only" (and must comply with FDA requirements for such use) or must have been approved or