Archive for the ‘General’ Category

Are most published research findings false?

Friday, October 7th, 2011

Many people are aware of the work of John Ioannidis regarding the analysis of research findings and the conclusions drawn from those analyses.  In particular, these concepts were described by him in a paper published in PLOS Medicine in 2005 is apparently the most downloaded article from that journal.

I’ve had this article on my mental favorites list for some time now.  I am finally putting a few words in print about it mostly to put a stake in the ground on this issue because I believe it is an important one in this era of high volume research reporting.  In short, I agree with the article’s main conclusions, although I might phrase it as “most published biomedical research conclusions are not true”.  This is not to say I think there is some conspiracy or that statistics are useless.  To the contrary:  statistics is an enormously useful field of applied mathematics.  I also think a great deal of very good research is being done in labs and clinics around the world by very dedicated and smart researchers.

My concern over the veracity of biomedical research and how these results are reported stems from the nature of statistical models and test versus how they are interpreted and reported.  Within that discussion is another around the unspoken assumptions underlying both our biological and statistical models.

Perhaps the stickiest issue for me is the use, or misuse, of p values in many published studies.  Without getting too long-winded about it, far too often the p value is used all by itself and given the status of a “stamp of approval”.  Using a p value in isolation (i.e. p=0.001 therefore I won!) is ignoring a lot of important information.  What type of test did you “win”?  What distribution of p values for this test did you assume?  Are your assumptions correct?  Did you keep testing data until you found the p value you were hoping for?

Fortunately, I think the wider scientific community is waking up to the deficiencies in the most commonly used statistical analysis scenarios.  This recent article from Genomeweb does a nice job describing the basic appropriate role for statistical analyses in biomedical research.  An important distinction pointed out in their article is that statistical significance and biological (or clinical) significance are two different things.  When we rely on statistics to identify important relationships within a vast ocean of information, it is all the more important to understand what these mathematical tools are telling us.

As the wise scientist once said, “Never assume anything other than a 4% mortgage.”  I mentioned assumptions above in the sense of statistical models; assumptions also come into play in experimental design.  My sense of it is that these assumptions are usually underappreciated or perhaps even ignored.  The danger, of course, is that incorrect assumptions, statistical or experimental, can invalidate the results and conclusions of any research.  Often these assumptions difficult to verify, which we might be able to cope with, if we knew what these assumptions were.  Unfortunately, they are not part of the standard scientific reporting paradigm.  This recent article in PLoS Computational Biology sheds some light on the issue of reporting experimental assumptions.  Again, by bringing the issue to light there is hope that we can begin to change our science reporting procedures to incorporate some discussion of assumptions.

I find it reassuring that these discussions about accurate analysis and reporting of scientific research are surfacing.  Opening up communication about these critical issues will greatly enhance our ability to navigate through the ocean of biomedical studies available to us.

US Dept of Justice Doesn’t Like Gene Patents Either

Monday, November 1st, 2010

The US Department of Justice just filed a Friend of the Court brief, in which they assert that the native sequence of human genes should not be patentable in their view.  The story was published by Genome Web this morning and can be found here.

Personally, I agree.  It does not seem to me that anything inventive happened at the University of Utah to allow them to own the sequence of the BRCA gene in any sense.  Further, it is my feeling that a free and accessible human (or other living organism) genome will spur a great deal more innovation than needing to pay to use it.

ESHG Chimes in on DTC Genetic Testing

Friday, September 3rd, 2010

The European Society of Human Genetics (ESHG) published a policy statement in the European Journal of Human Genetics on the Society’s position with respect to Direct to Consumer Genetic Testing services .  In this position paper the ESHG discusses its position with respect to DTC advertising, quality, supervision, counseling, consent, privacy, and more.

Overall, the authors present cogent arguments for their views about how to handle DTC genetic testing.  The authors open by affirming that individuals have the right to know information about their genetic makeup, a point that I have not seen argued yet.  Then the authors tackle advertising of DTC services and quality of DTC services.  In both cases I, like the ESHG, think the DTC companies leave much to be desired.

The following paragraphs of the position paper from the ESHG espouse supervision of all genetic testing by medical professionals, mandatory counseling, and a significantly more involved informed consent process.  These views from the ESHG seem pretty conservative to me, to the point of being paternalistic.  In fact, the authors state that the “right to know” needs to be balanced against “the need to protect the same individuals from inappropriate genetic information”.  Keep in mind that the ESHG has an interest in enhancing the public perception of genetic testing.

While their viewpoints are valid ones, they seem to me to reflect the current status quo and to lose the potential for discovering new uses for genetic information in healthcare that may result from “open horizon” creativity.  To be sure, the entrepreneurial attitude that characterizes the DTC genomics/genetics companies now comes with risks, but its exploratory character can result in quantum leaps in understanding.  The diminished quality and partial truthfulness of these young companies struggling in a new industry can be hazardous to society, but at some level we need to take risks like those in order to advance.  The secret, I believe, is to balance the liberty with restrictions in order to control the risk to society and its individuals as best as we can.

The good news is that this is exactly the kind of public conversation we should be having about how to handle this new area of medicine.

UC vs NPG, continued…

Friday, August 27th, 2010

I have to confess that I agree with the excerpt quoted below from the UC rep.  Hopefully this saga portends future progress in the scientific publishing field.

From http://www.genomeweb.com//node/948284?hq_e=el&hq_m=798093&hq_l=3&hq_v=a2a10fac80:

“Laine Farley, who directs UC’s California Digital Library, tells USA Today that the current journal model, under which researchers ‘contribute the labor to produce the articles that go into these journals, they do the peer review, they often are editors, and then the institution has to buy back the access to the output of their research,’ is not acceptable, and ‘needs to change.’ “

Genomic-level Testing: the Debate Continues

Friday, August 20th, 2010

This is an interesting debate unfolding here: what to do about Direct To Consumer (DTC) genetic/genomic testing.  The two sides seem to be

  • It’s my DNA and I want to know what’s there
  • You may not get correct information on your DNA and what will you do with it anyways?

I don’t think there is substantial objection to an individual knowing what the sequence of bases is in their DNA, however, the technical adequacy of DTC tests is an issue.  Will you receive the correct information about the sequence of your genes?  At this time, that is not assured.

The second big issue, and the one that has the greatest implications for health care delivery in the future, is how genomic information will be used.  I’m fine with people sequencing their own DNA, but what happens next has implications for those beyond the individual who had their DNA sequenced.  As pointed out by Annes and colleagues in NEJM (Risks of Presymptomatic Direct-to-Consumer Genetic Testing, 18AUG2010), there could be liability and other issues for the physician to consider when a patient brings in their DNA sequence information for consideration.  If the utility of that information is uncertain, then many unanswered questions will linger.  In their example, what if the 30-year old man presents sequence data with a “prostate cancer risk allele”?  The clinical utility of such information is currently unknown.  Does the physician order additional testing (and thus incur additional health care costs) or does the physician take no action.  What if the physician takes no action and some years later the patient is diagnosed with prostate cancer?  Is the physician liable?  If the decision to sequence one’s own DNA affected only the individual I think there would be little objection to the expenditure.  But it doesn’t affect just that individual.

The implications for our healthcare delivery system of the shifting of health care information access, as exemplified by DTC genomic testing, are also interesting.  In a certain sense this debate is the most visible current example of the ongoing negotiation between healthcare consumers and providers regarding ownership and cost.

As pointed out by Evans and colleagues, (Preparing for a Consumer-Driven Genomic Age, also in NEJM on 18AUG2010), patients increasingly know more than their physician about specific genetic topics.  This shift has been enabled by widespread internet access.  This empowerment of consumers by transfer of knowledge ownership from doctors/healthcare professionals/industry to patients should rebalance the value equation in favor of patients/consumers.  This in turn will reduce the cost of health care in the long run.

What this blog is about and how it will run

Thursday, November 5th, 2009

I added this blog as a place for me, those I work with, and people interested in similar things to have conversations around science, in particular biological science.  I believe strongly in communication, that it is one of the most powerful tools available to individuals to shape the world around them.  I also believe that honest communication, in a balanced, respectful manner, is the shortest path to the truth on any given matter.  Go ahead and be controversial here, but do so respectfully, please.

Because this blog is attached to my company’s site and I administer it, I will shamelessly dictate the conversation focal points.  Although I will be open-minded about posts and comments, because this blog is associated with my company, posts and comments that are outside of the range of what most people would consider appropriate will be removed.

Here are the sorts of things that I will blog about, and hope that readers will contribute their thoughts about:

Communicating science.  How is this best done?  How can it change for the better?  In this category, data analysis and interpretation are of particular interest to me.

The process and philosophy of science.  How science is practiced.  What are its flaws?  How does it enable us to reach beyond ourselves?  What are the ethics around science and what do they mean anyway?

Education around science and medicine.  We are, after all, usually attempting to educate the recipients of our communications.  While I enjoy science in its many aspects, many people don’t think of science as one of the focal points of their life.  In fact, many would prefer if they could avoid it entirely.  Is science education necessary for everybody?  How much science education is enough?

The adventure of starting a new thing.  Whether it’s a company or some other endeavor, there are some gratifying, frightening, and surprising moments as th story is written.  To that end, this blog may become something of a diary.  I hope the reader will help add to the story of VMWA.

I hope what you learn here will change your life for the better in some small way.  Enjoy!