NHGRI Long-Range Planning - Comments

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


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Comments on "Revised White Paper #1: Applying Genomics to Clinical Problems - Diagnostics, Preventive Medicine, Pharmacogenomics "

Now that the genome has been mapped, attention and funding needs to be directed to figuring out how to treat/cure horrific genetic disorders. Please focus on the critical life-sustaining proteins, the by-products of genes. I'm told there aren't many genes that are life-sustaining. Focus on single gene, orphan disorders and identify where life-sustaining proteins live in the cell, how long they are functional before being recycled etc. Perhaps TAT fusion proteins can be used to deliver synthesized proteins intracellularly if we knew a great deal more about the proteins themselves. Focus on neurological genetic disorders and how to globally deliver a healthy gene to the nerves in the central nervous system. There is really little else in life that matters when children are dying horrific deaths from disorders that are treatable, given attention and funding. My five year old has Giant Axonal Neuropahy, GAN. Scientists know exactly what causes GAN. It's caused from a single gene mutation. Both upper and lower motor neurons are impacted just like in ALS, SMA, INAD, Friedreich's Ataxia and GAN, to name a few... Figure out how to treat disorders of the central nervous system by learning more about life-sustaining proteins of the CNS. A great deal of money is spent annually on ALS research whose cause remains elusive. Scientists feel even the 10% of ALS patients with the SOD1 gene mutation also have mutant neighboring genes causing the disorder. Focus on simple, single gene neurodegenerative disorders like GAN, as they may hold many of the answers to the elusive, complex disorders like ALS. I could go on, and on for days. I'm willing to travel anywhere, anytime to express this large unmet medical need and the need to redirect funding to it. Please use the gov't genome scientists to help solve these ravaging disorders. As horrific as it is for a parent to hear their child has cancer, at least there are treatment options and medical protocol to offer hope. This is not the case when you are told your child has a neurological genetic disorder. You are sent home to try to figure out how to live watching your child progess to the point of being a quadriplegic, dependend on a feeding tube and ventilator before dying in the teenage years or early 20's. The Gov't needs to do something about this, and the Genome scientists can focus attention to the critical proteins needed to sustain life. I beg you to not spend money and resources on the "fluffy", "feel-good" stuff discussed in this white paper. "Genetic predispositioning", "impact to physician workflow", "stigma" and "how to interpret results" etc. really means nothing when there are little treatment options available anyway. Please forward this feedback to whomever you feel has the ability to make certain precious funds are not wasted. Please forward to whomever within the NIH who has the ability to make a difference in the precious lives of many.

(256) Monday, May 4, 2009 3:19 PM


This suggestion may not fall within the scope of the NHGRI. Studies must be conducted to identify health behaviors that may be associated with a decreased or increased risk of cancer in the presence of a specific genetic mutation (e.g. Are fiber consumption, calcium supplementation, body fatness, level of physical activity, smoking, and alcohol intake associated with incidence of colon colon cancer among unaffected carriers of MLH and MSH mutations?).

(259) Tuesday, May 5, 2009 1:26 PM


I think that a knowledge management or clinical content development lifecycle model should be considered in identifying the process in which genomic information/results are taken from the research environment to the lab, clinician, and patient with regard to to: 1) translation of genetic variant results to meaningful Rx implications 2) identification of benchmarks and relavent evidence that supports genetic variant information (so it provides context for clinician and ultimately pt) 3) development of clinical decision support (CDS) rules that incorporate evidence in identification of pts based on results, identification of supporting documentation, and educational resource information at the point of care This incorporates CDS with EMR adoption, and can (and is being done in a limited basis at organizations such as Partners Healthcare.
Lastly-- providing the feedback (data regarding treatment options/outcomes) as additional research opportunities is critical in studying the integrated data that will be increasingly available (clinical genetic data and interventions).
Also, pharmacogenomics with regard to medication intervention treatment and surveillance with regard to identifying at risk populations for adverse events (as well as benefits) is another area that will be emerging-- The initial efforts of the Sentinel Initiative development can provide the framework for this area (and provide opportunity for research/surveillance efforts to influence clinical care. I have been involved in both of these areas (knowledge management for CDS and pharmacovigilance in clinical research)

(265) Tuesday, May 19, 2009 11:07 AM


The most critial obstacle is that we do not know the underlying biological meaning for all these identified common variants. First, we should identify most of these independent variants in each identided gene. Secondly, we should characterize the effect of these common variants on diseae risk and health. If certain genetic variants of them pass certain threshold, we should incorporate them in our medical practice. So, a constellation of these selected variants could be used in decision-making (risk prediction, aiding drug/treatment-selection).

(272) Saturday, May 30, 2009 5:30 AM


Research regarding how and when to incorporate genetic counseling into preventive/genomic medicine is essential, especially given the knowledge and time limitations of current primary care providers. Genetics counselors' unique training and skills positions them to have a potentially significant role in the facilitation of genomic-based preventive medicine through expert patient and provider consultation and risk communication. The provision of health & screening guidelines based upon a diagnosis is already part of routine genetic counseling practice and does not conflict the practice value (not principle) of non-directiveness. Consideration should be given to new or modified funding mechanisms to support research in this area by genetic counseling professionals - most of whom do not hold a doctoral degree and many of whom do not have faculty appointments.

(276) Monday, June 1, 2009 3:57 PM


My comments below are to the last 3 paragraphs of section #6.
A way to balance the integration of the non-directive ideal of genetic counseling with the more directive world of clinical medicine is to collaborate with the interpersonal realm of clinical nursing. Not all patients or clinicians view the non-directive approach or the more directive approach as the ideal method of counseling. In fact in genetic counseling patient and families should be able to tell their story. Patients and families need to engage in the counseling process. Although there are special situations in which a more directive approach in counseling is appropriate, let the patient seek or ask for it or consent should be sought by the clinician from the patient as "...would you allow me to be more directive in this instance...because this information is concerning...." Pause for the permission then proceed. The more the clinician uses this strategy, the less s/he will find it necessary to use the more directive approach. Role play each potential counseling session with staff. Just because you have counselled lots of patients in different genetic situations does not mean that all counseling sessions will be the same from now on. Experience counts but individual genetic stories are unique, therefore the clinician needs to be respectful of the patient as the author and the stakeholder of his/her genetic story.
The day will come when genetic testing strategies will no longer be entirely clinician-dependent. Technological and communication advances is shaping the role for direct access by patients and the public to genetic testing or extensive genotyping information. Clinicians will be better prepared to respond to individual patients who obtain sequence information (or extensive genotyping information) independently and present it to their doctors with concerns about the health impact of newly-identified variants by heeding the A-B-C-D of patient-clinician/doctor relationship (Wilson-Stronks and others 2009): "A" stands for Accommodating the needs of all patients; "B" stands for Building a repertoire of sociocultural competence; "C" stands for Collaborating or Consulting with other clinicians; "D" stands for diversifying resources, mixing methods of counseling using qualitative and quantitative methods of interviewing through structured or non-structured counseling, face-to-face, electronic, or a combination of face-to-face and electronic counseling, data collection and analyses.
Funding agencies and/or those holding patents on genetic tests must on their own volition support reduced costs or cost-free testing for "rare" diseases, coordination of guidelines on genetic testing, and educational programs for patients and clinicians or "someone" or "some entity" will do it for them. The global economy will be unable to afford disparity in costs of testing and appropriate interventions among all those likely to be in need.
These valid questions deserve valid comments. Let's hope that the totality of the diverse comments will garner useful answers to these questions. Thank you.

(284) Wednesday, June 10, 2009 3:12 PM


Despite my attendance at related conferences and meetings, and my awareness of this particular website, I still received most of my own practical information about DTC from a segment on Oprah.
There does not seem to be a link to information for consumers re: DTC screening on the NHGRI site, or at least not easily located by me.

(304) Tuesday, June 30, 2009 12:22 PM


From a payer perspective, coverage decisions for all types of tests (clinical testing, preventative testing, diagnostic testing, etc) require a high level of evidence as new genomic diagnostics and technologies become commercially available as they have the capability to inform medical decision making. The evidence must be original study data (e.g., well designed clinical trial, observational study), a systematic review, or a meta-analysis and is published within a peer-reviewed publication. Conference abstracts, editorials, and expert opinions are generally not considered for evidence review. In many instances, new genetic technologies and other clinical testing come to market with little evidence. It is not always clear how the test results are to be used and what the expected outcome should be. In general, proven interventions should be available to justify genetic testing. Other types of data (e.g., morbidity and mortality data following use of a genetic test) can be considered but may be limited if the test application is based on pathophysiologic reasoning only. Evidentiary standards are lacking for genetic tests. Many payers follow the Center for Disease Control's ACCE model as closely as possible. This model allows taking into account data regarding analytic validity, clinical validity, and clinical utility as well as social/ethical data. Clinical utility data is significant in looking for evidence that a genetic test can improve patient outcomes. Evidence that a test can be used to inform treatment decisions compared to current management without genetic testing is most influential. Unfortunately, many tests are marketed and advocated based on limited clinical data with low quality evidence. Analytic validity data is usually not published. Lastly, shortcomings exist in ways to evaluate laboratory medicine quality around genetic tests. Standards need to be tightened.
While analytic and clinical validation are the primary focus, evidence that a genetic test leads to reduced healthcare costs is helpful information to have when evaluating genetic tests. The expectation for most personalized medicine products is that they hold the promise for better patient management and improved outcomes through health decisions that are based on knowledge of an individual's genetic make-up and particular disease. These improved outcomes can potentially lead to cost savings (the savings may not be realized immediately). This type of data is helpful to the industry as a whole but from a payer perspective, cost information is never solely used to make coverage decisions. Payers generally do take into account that many genetic disorders are rare and may have little published data to support testing.
Public and private payers are increasingly recognizing the value of new genetic technologies. Private payers are often more quick to perform an evidence review of these technologies for coverage determinations; in turn, this could facilitate or inhibit coverage and reimbursement more quickly.
How can costs of testing, including associated costs of interpretation and education, be kept low? How can appropriate access to new genetically-based tests be ensured for all patients regardless of type of health care coverage? Current testing is costly due to the nature of venture capital dollars frequently being the economic backing for development of the tests. This may lead to the need for a quick and high ROI for the investors. If clinical validation accompanied the marketing of new tests, third party payers would be encouraged to provide access. Currently, significant healthcare dollars are wasted on unproven and unnecessary testing which do not inform medical decisions. Should that be remedied, the dollars needed for appropriate testing would be less of an issue.
How can cost-effective arrangements be made for obtaining proprietary tests that are currently too expensive for most consumers and payers? What strategies are needed to ensure that future genetic discoveries lead to affordable tests? How can the intellectual contributions to their discovery be appropriately recognized and developmental costs reimbursed while keeping costs within reach? Again, if the testing were limited to clinically proven applications, then the overall costs to the system may not be as problematic. Since this remains an issue in the device and pharmaceutical areas, it is doubtful that the molecular diagnostic area will have any more success in solving this problem.

(307) Tuesday, June 30, 2009 2:42 PM


We wish to reaffirm our concerns, which do not appear to have been addressed in this revision. Specifically, we believe it is misleading to organize the document into separate questions about what information will convince payers to reimburse genetic tests and about what information will convince providers to apply genetic testing strategies to their patients.
First, the questions do not make it clear that not all available genetic tests are equally likely to result in useful medical information and improved clinical outcomes for the patient. Second, evidence of improved clinical outcomes as a result of genetic testing is as important to providers as it is to payers- both groups have the goal of improving patient health efficiently and cost-effectively and ultimately is of utmost importance to patients.
Rather, we suggest addressing the overall goals when considering adding genetic testing to standard clinical care, the evidence needed to show that those goals can be achieved for individual patient applications, and how tests with evidence of clinical utility can favorably impact payer policy, provider use, and patient acceptance i.e. all users.

(310) Tuesday, June 30, 2009 8:57 PM




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