The Huntington's Disease Society of America (HDSA) has recently released their "Genetic Testing Protocol for Huntington's disease" intended to update previous guides. Work on this document followed an HDSA review of Centers of Excellence that showed a variation among centers regarding procedures and relative number of premanifest individuals tested at each site. There are several differences from the previous guide to the updated protocol, some of which are intended to make the genetic testing process more flexible and assessible. However, some of the wording, including the choice of "protocol" instead of "guide" or "guideline" and "must" or "should not" as in the testing for juvenile disease suggests a more dogmatic approach.
Two points to make from the beginning: Guideline development is (very) hard and there will always be differences of opinion..
What is a protocol, and how does it differ from a guideline? "Protocol" usually implies a rigid process such as a protocol for a clinical trial, or a hospital procedure like getting a blood transfusion. However as defined by HDSA, their protocol is a framework of recommended procedures . . . and not regulations . . . recognizing that each testing situation is unique. Seems ambiguous. "Guide" or "Guideline" implies a set of recommendations or suggestions that are to serve as an educational tool, that may apply to many, but specifically not to to all situations. International and European groups use "best practice guideline" terminology in their recommendations for genetic testing. There most recent document was published in 2013.
What process was used to develop the protocol? Based on the description, it appears that the generally accepted processes for guideline develpment for medical situations may not have been followed. The recommended process, which is being followed by the present guideline group from the combined behavioral working groups of HSG and EHDN is much more labor intensive includes:
- Transparency: We are not told how the 16 experts were chosen. These HDSA recommendations are based on a small group's expert opinion. Opinions of a larger group of experts were not solicited and may substantially differ (or not).
- Review by the larger community: This usually includes review by a larger goup of experts (doctors, genetic and mental health counselors, social workers, etc), individuals with HD or at risk for HD and their families. This step decreases the chances for any biased opinion of the smaller group. For instance, the European guide developed by an initial committee of 22 members from 12 countries was posted on the European Huntington's Disease Network (EHDN) for review and comment and to larger in person presentation at EHDN and World Congress meetings. These additional steps don't automatically mean "better" recommendations, but it allows for more opinions to be expressed and considered.
- Response/revision: This incorporates the larger consensus review into the final document
Not following the generally accepted process does not mean that the final protocol is flawed, but that it might not be as "trustworthy". Trustworthy is the term used by guideline developers.
What is different in this protocol than earlier HDSA guides?
- Stronger language as implied by the use of "protocol" and "must"
- First interview for predictive testing is by phone (this is different from European guidelines)
- Only two in-person visits, first of which includes giving blood, second of which is getting the results; this is also different from European guidelines which leave it up to centers
- A neurologist exam is not required (this is similar to European guidelines)
- Updated intermediate allele information (similar to European guidelines)
What about testing for JHD? Why not offer "non-disclosure" testing in appropriate situations
It is problematic how little guidance is given (by HDSA or any other organization) for gene testing a minor for juvenile onset of HD. The language used by HDSA is "a child should not be tested unless exhibiitng symptoms that cannot be attributed to another condition" may not be particularly helpful for families in distress. It would probably have been more useful to clinicians and families to give guidance on factors that would influence the experts decision to test for JHD. Factors like steady cognitive decline on standard or neurocognitive testing over time, decreasing ability to participate in usual physical activities, seizures, and neuropsychiatric symptoms.
The present clinical decision is based on risk to the juvenile by a test result that predicts an age of onset later in life. However there are harms associated with not testing a juvenile onset individual, such as pushing the child to perform better than is possible.
Why not offer a "non-disclosure" protocol for testing of a juvenile? Such a protocol (including education and informed consent of parent) would require (if it can be obtained) a positive family history and symptoms that could be consistent with juvenile onset. The non-disclosure part of the protocol would limit risk and includes testing with only 2 possible results:
- Yes, it is JHD: A "positive" test result is disclosed: "Positive" is defined by a CAG count in the juvenile-onset range which would be disclosed to parents and child (if appropriate). Importantly this allows for appropriate expectations and care of the child.
- No, it is not JHD: A "negative" test result. "Negative" is defined by any other CAG count, whether in normal. intermediate or definite later onset disease. The CAG count is not disclosed and results would be confidentally sealed. Harms would be no greater than that of the 50% at risk population. And importantly it allows for appropriate expectations and care of the child.
Center-centric genetic testing guidelines: At least in the U.S. the vast majority of individuals with, or at risk for HD do not/cannot get to centers who have genetic counselors, neurologists, psychiatrists, social workers, etc. and indeed most get their care from general physicians. Do these guidelines address the needs of this larger group? Though guides for the generalist may be harder to develop, center-centric, center only testing guidelines aren't assessable or flexible enough to help the majority of at risk individuals who might choose predictive testing.