By Rachel A. Hardy, MA, RAC

The federal Department of Health and Human Services encompasses many agencies, each promulgating its own sets of regulations. At times, these regulations appear to contradict one another. On 7 April 2014, a rule issued by the Center for Medicare and Medicaid Services, the Centers for Disease Control and Prevention, and the Office of Civil Rights modified the CLIA (Clinical Laboratory Improvement Amendments) regulations to allow laboratories subject to CLIA to provide patients “with copies of completed test reports” (DHHS, 2014, p. 7290).

Late last year, the Food and Drug Administration issued a warning letter to the company 23andMe for not obtaining marketing clearance or approval for the 23andMe Saliva Collection Kit and Personal Genome Service (PGS). It stated “assessments for drug responses carry the risks that patients relying on such tests may begin to self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome of the assessment. … Serious concerns are raised if test results are not adequately understood by patients or if incorrect test results are reported” (FDA 2013a).

Senator Lamar Alexander saw inconsistency between these two recent actions of DHHS agencies regarding patient access to laboratory test results. Senator Alexander expressed his concerns in a 20 Feb letter to FDA Commissioner Margaret Hamburg. In the letter, the senator applauded the CMS rule that promotes sharing of test results directly with patients while he criticized the FDA because it does “not trust individuals with test results.” He describes these two rulings as “conflicting.” He questioned the “agency’s commitment to making personal health information available to support medical innovation” (Alexander L 2014).

At first glance, it might seem that these two agencies’ actions are at cross purposes. One supports patient access to test results and the other does not. However, a closer look reveals that Senator Alexander is comparing apples—CLIA regulated laboratories, with an orange—23andMe. 

CLIA began in 1988 as a way to establish standards for clinical laboratories. The CLIA definition of laboratory is “a facility for the…examination of materials derived from the human body for the purpose of providing information for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, human beings.”(42 CFR 493.2(d)(1)(3) 1995). These regulations cover all aspects of laboratory testing, including a list of to whom laboratories can report results. That list did not include patients until the April modifications, which allows “laboratories subject to CLIA, upon the request of a patient (or the patient’s personal representative) to provide access to completed test reports that, using the laboratory’s authentication process, can be identified as belonging to that patient,” (DHHS, 2014, p. 7292).

Started in 2006, 23andMe is “dedicated to helping individuals understand their own genetic information using recent advances in DNA analysis technologies and web-based interactive tools.” The company states on the very top of its home page: “The largest DNA ancestry service in the world.”  However, 23andMe is not a laboratory; for testing DNA, it hires a laboratory with CLIA certification, which the company cites as evidence of “the quality of data” it has given to customers. 

So, it appears the senator is wondering why a regulation for laboratories is so different from the regulation applied to 23andMe, which is not a laboratory. One difference is the CLIA laboratories make the initial report of test results to the physician or other health care provider. Commenters on the draft CLIA rule expressed concerns that patients would interpret their test results without physician involvement. CMS responded:  “We expect that patients will continue to obtain test results and advice about what those test results mean, through their ordering or treating providers.” (DHHS, 2014, p. 7292).

By contrast, the FDA’s warning letter expresses wariness about patients receiving genetic information as part of a direct-to-consumer test: “False genotype results for your warfarin drug response test could have significant unreasonable risk of illness, injury, or death to the patient … . These risks are typically mitigated by International Normalized Ratio (INR) management under a physician’s care. The risk of serious injury or death is known to be high when patients are either non-compliant or not properly dosed; combined with the risk that a direct-to-consumer test result may be used by a patient to self-manage, serious concerns are raised if test results are not adequately understood by patients or if incorrect test results are reported” (FDA 2013a).

Does the FDA want to keep all test results from direct patient access, as the senator implies? I think not. The warning letter addresses the particular case of 23andMe’s PGS. The agency wants to mitigate the risk of direct patient access to potentially high-risk test results. The agency classifies new medical devices as high risk, or Class III, unless the sponsor provides evidence that supports that the device is moderate risk (Class II), or low risk (Class I). FDA mentions that if 23andMe modified the device labeling in the way that FDA suggested, risks could be mitigated so that PGS would be classified as Class II or I “and not PMA (premarket) approval,” which would require clinical trials (FDA 2013a) (FDA 2013b) (FDA 2012). After receiving the warning letter, 23andMe suspended … health-related genetic tests  pending FDA regulatory review, according to its Health page. The same page explains how this affects customers. New customers will receive “ancestry-related information and raw genetic data without 23andMe’s interpretation.”

So, these two actions coming from DHHS are not contradictory because they are responses to two distinct situations—apples vs. orange. The CLIA rule was changed to give direct patient access to test results from CLIA-certified laboratories, where patients were likely to speak with the health care provider who requested the test—a low-risk situation. FDA sent the warning letter resulting in suspension of patient access to genetic test results regarding potential disease and drug-responses because it was a direct-to-consumer test where no health care provider was necessarily available—viewed by FDA as a high-risk situation. It is reasonable to debate the relative risks posed to consumers/patients by a direct-to-consumer service vs. one in which a physician is involved. However, it is simplistic  to conclude that the same rules should apply to both situations.

 

Rachel A. Hardy, MA, RAC, is a data management technician in oncology at Duke University and a member of NCRAF. She has six years of experience applying cGCP, including clinical operations, in a clinic, and medical writing. She can be reached at [email protected]

 

References

 

US Department of Health and Human Services. CLIA Program and HIPAA Privacy Rule; Patients’ Access to Test Reports. Federal Register Vol 79, No. 25, Thursday, Feb. 6, 2014, pp. 7289-7316. http://www.gpo.gov/fdsys/pkg/FR-2014-02-06/html/2014-02280.htm. Accessed 7 May 2014.

US Food and Drug Administration. Warning Letter. To Ann Wojcicki, CEO. 23andMe, Inc. 22 Nov 2013. http://www.fda.gov/iceci/enforcementactions/warningletters/2013/ucm376296.htm Accessed 8 May 2014.

Alexander L. Alexander Calls for Administration to Clarify Position on Patient Access to Personal Health Information. 20 Feb 2014. http://www.alexander.senate.gov/public/index.cfm?p=PressReleases&ContentRecord_id=1fa364a5-3a14-4cce-b2ed-9940c033aac3. Accessed May 6, 2014.

Public Health. Centers for Medicaid and Medicare Services. Laboratory Requirements. 42 CFR §493.2(d)(1)(3). Revised 24 Apr 1995. http://www.gpo.gov/fdsys/pkg/CFR-1997-title42-vol3/pdf/CFR-1997-title42-vol3-sec493-2.pdf Accessed 8 May 2014.

23andMe Home page. https://www.23andme.com/ Accessed 8 May 2014.

23andMe About page. https://www.23andme.com/about/corporate/ Accessed 8 May 2014.

23andMe. 23andMe Provides An Update Regarding FDAs Review. 5 Dec 2014. http://blog.23andme.com/news/23andme-provides-an-update-regarding-fdas-review/.  Accessed 8 May 2014.

US Food and Drug Administration. Overview of Medical Device Classification and Reclassification. 17 Dec 2013. http://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cdrh/cdrhtransparency/ucm378714.htm.  Accessed 7 May 2014

US Food and Drug Administration. Premarket Approval (PMA).24 Jan 2012. http://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/premarketsubmissions/premarketapprovalpma/default.htm. Accessed 7 May 2014.

23andMe Health page. https://www.23andme.com/health. Accessed 8 May 2014.

 

Copyright 2014 by Rachel A. Hardy