Resistance is Futile

I was reading some peer review comments of an article I am submitting and it got me thinking.....How can we combat certain resistant to change mindsets? For example from the anonymized reviewer:


I strongly disagree that because there aren't currently sufficient numbers of genetics providers (even if you add up clinical geneticists and genetic counselors, as suggested above) that this means that the only solution is to move genetics into primary care. ...........




Ok, you can disagree.....but.....when you say this......


First of all, the demand for genetics services has not yet led to long waiting periods or other crises.

Ever tried to get into a cancer genetics or clinical genetics office in less than 1 month? More likely less than 3 months. That being said...even this reviewer acknowledged that there is not a massive amount of referrals.......

What number of trained genetics providers are needed and what are the barriers to educating, producing and hiring more and supporting their work?

Ahh....trade secrets that I will be publishing soon......





Can the authors imagine another group of specialists (for example, brain surgeons) deciding that there aren't enough knowledgeable brain surgeons, so primary care providers need to be trained (via a short course, perhaps) to do brain surgery?


The term is Neurosurgeon....and this argument is a fallacy..... They trained for 7 years and brain surgeons don't operate on Alzhemier's


I think statements about moving genetics into the primary care arena need to be much more carefully thought through and evaluated -- what are the outcomes likely to be associated with the suggested interventions??





Other than earlier pick ups in cancer predisposition, MI predisposition, adverse drug reactions, improved medication dosing, more cost effective utilization of care, less "loss of chance" malpractice....I could go on and on.....but I won't





The Sherpa Says:


This is the resistance we face ladies and gentlemen. Why do I have to learn something, just because there aren't enough specialists???? There is something called continuing medical education.......just because they didn't discover DNA when you were in medical school, doesn't mean you don't have to learn about it........Resistance is Futile....

When you know the Books are Cooked

I finally had a chance to sit down and review Genetics in Medicine for the month of June. Yes, I am a month behind.....leave me alone. I have been doing some other things for the last few weeks........So take it easy on me.....

Have you ever had the feeling that the results of a study need replication? Especially because the results do not match up with clinical reality. What am I talking about?....Wylie Burke's study on how many PCPs have ordered a genetic test. There is an age old adage that on self-report tests for anything....you will get 2 answers.....80-85% and 15-20%.....By that I mean, most physicians don't want to say they do something all the time, or none of the time.....By that I mean, most physicians lie on self reports.....even when anonymized....

This is why I saw malarky on this study, recently published....

Methods: Survey of a random sample of 2000 primary care physicians in the United States (n = 1120,

62.3% response rate based on eligible respondents) conducted in 2002 to assess what proportion have (1) ever ordered a genetic test in general or for select conditions; (2) ever referred a patient for genetic testing to a genetics center or counselor, a specialist, a clinical research trial, or to any site of care.

Results: Nationally, 60% of primary care physicians have ordered a genetic test and 74% have referred a patient for genetic testing.

Approximately 62% of physicians have referred a patient for genetic testing to a genetics center/counselor or to a specialist, and 17% to a clinical trial.

Minority-serving physicians were significantly less likely to have ever ordered a genetic test for breast cancer, colorectal cancer, or Huntington disease, or to have ever referred a patient for genetic testing relative to those serving fewer minorities.

Conclusions: Reduced utilization of genetic tests/referrals among minority-serving physicians emphasizes the importance of tracking the diffusion of genomic medicine and assessing the potential impact on health disparities.

OK, Wylie, you are an excellent physician scientist, but you know this to be intrinsically garbage. If even 30% of PCPs referred just one patient for services, then the entirety of the genetics community would be rapidly overwhelmed.

I would bet that those tests sent off were Factor V Leiden tests for hypercoaguability work up(Now considered fairly worthless tests post clot)

There is no way 74% of PCPs even know a geneticist to refer to. This study is so flawed and I am embarassed to see it actually passing peer review. Who in there right mind would believe any of these data.

74% is awfully close to 80%....this is a fishy smelling study and I am blown away that it got published.

How did I know that they probably didn't sense the anomaly I did? Because they are all PhD's not a single community based doctor in the bunch......

Damn!

The Sherpa Says:

If you believe this study, then I have a bridge to sell you.........Further proof, you can't always believe what you read....Not much has changed in 5 years since the NEJM study, so I doubt that this study is true.

276 pages of pure reality!

Have you read it? Come on.....You didn't. Well, you are missing out. Back in 2004 I started watching the Secretary's Advisory Committee on Health, Genetics and Society. But even more importantly I began watching back meetings that were webcast, including the SACGT. I studied the players in the field, the advisors, the government. I began to notice trends and agendas.

This is why I saw all of the regulations coming. I began emailing members, speaking with advisors, and learning how and when all of the issues would arise and then be solved. Then in 2005 I began to develop the business plan for Helix Health of Connecticut.

The safest climb to the summit is with trained genetics professionals like the ones we have. The riskiest is D-I-Y. The SACGHS is against D-I-Y...notably this 276 page report goes into this in fine detail.

Highlights include

Are Genetic Tests Special?

When considering whether genetic testing is different from other laboratory tests, it is important to understand the viewpoint known as "genetic exceptionalism," the perspective that genetic information is unique among health-related information and therefore deserves special considerations and protections. Proponents of this perspective usually point to the following features of genetic information as being distinct from other types of health information:

• It can be used to make predictions about an individual’s health future.
• It does not change throughout a person’s lifetime.
• It has the potential to reveal information about family members.
• There are instances in which it has been used to discriminate against individuals or selected populations.

But.....

....... a nonexceptionalist approach has been taken with respect to Federal health privacy protections. The Federal Health Information Portability and Accountability Act Privacy Rule, which became effective in 2003, treats genetic information as equally sensitive as other medical information and provides the same level of protection to genetic and other types of personal health information. Recent policy recommendations encourage movement away from genetic exceptionalism.

That Being Said....

The Committee is concerned by the gap in oversight related to clinical validity and believes that it is imperative to close this gap as expeditiously as possible. To this end, the Committee makes the following recommendations:

A. FDA should address all laboratory tests in a manner that takes advantage of its current experience in evaluating laboratory tests.

B. This step by FDA will require the commitment of significance resources to optimize the time and cost of review without compromising the quality of assessment.

C. The Committee recommends that HHS convene a multistakeholder public and private sector group to determine the criteria for risk stratification and a process for systematically applying these criteria. This group should consider new and existing regulatory models and data sources (e.g., New York State Department of Health Clinical Laboratory Evaluation Program). The multistakeholder group should also explicitly address and eliminate duplicative oversight procedures.

D. To expedite and facilitate the review process, the Committee recommends the establishment of a mandatory test registry as noted in the following recommendation.

The Sherpa Says:

I will go into this report in more detail later. But If I was Google......This would be mandatory bed-time reading...Looking at these snippets it is clear. The barrier to entering the testing business is about to get MUCH, MUCH bigger. Playing nice with the government will only get you so far.

Archon X-Prize Here We Come

This week in the Proceedings of the National Academy of Science an article entitled:
"Single-molecule mass spectrometry in solution using a solitary nanopore" was published.

Why is this mouthful of words important? Well, the future of genetic testing and sequencing is going to change and this is the likely direction. This pore, created by a bacteria (Staph Aureus) is only 1.5 nanometers. For appreciation, the human hair is 10,000 nanometers. What I think is ironic is that the enzyme used to create the pore actually gives staph its ability to really make us humans sick. The technique used is remarkable...I don't know if anyone has seen a tandem mass spec before. But it usually takes up the size of a lab table. This procedure could actually be accomplished on a microchip!!! This study is a proof of concept study done in Ohio and Brazil which demonstrates the fidelity of molecule size prediction. I am sure there will be more to follow.

In addition Harvard has gotten into the game of nanopore sequencing and will likely be the world leader. But this is no surpirse. They have been in this nanopore game since the early 2000s (did I just say that?) The rough estimate for launch in this project has just gone from 7 years to 3.

The biggest problem clinicians have with genetic testing is it often takes too long with some of the quickest results taking longer than 6 hours. Nanopore sequencing could give answers in less than 2 hours. This would allow a physician to dose medicines, change treatments, identify disease in a much more reasonable window of time.

Do I see nanopore sequencing being used in the ED? Not quite yet, but the pharmacogenomic implications for personalized medicine are huge!!!!

Thanks Jason for putting this on the Radar Screen back in March.

Heart Risk Genes in Question

In the April 11th issue of JAMA Tom Morgan and Rick Lifton report a large "Replication" Study intended to identify at risk polymorphisms. I remember Tom running all over Yale collecting samples while I was a medical student rotating through genetics there. Personally I am surprised that the press did not jump all over this study. They evaluated 85 previously studied markers and found absolutely none were linked to increased risk of heart attack.
However family history of MI was higher in cases than controls, the racial subtype was Caucasian, the study identified each gene polymorphism individually. What this alerts me to is the shortcoming of candidate gene analysis (looking for genes based on mechanism of disease process). More importantly it puts an ALERT out that testing for MI predisposition is not ready for prime time quite yet, at least in a pan screening form. Perhaps nuanced testing in specific groups like ALOX5AP in Icelandic and Scottish patients will be the best way to stratify care.
The Gene Sherpa says- Hold on to testing for MI for now. Subgroup analysis will need to be done....again. Soon we will have whole genome analysis of risk genes and that will help solve this mystery. I hope Tom is doing well at Wash U St Louis. If anyone sees him tell him Steve Murphy says hi.