Traditional Rare Disease Diagnosis: Human Factors
With technological developments in medical tools, pathology, laboratory equipment, and diagnostics in general, why should it take so long to come to diagnostic conclusions? The Journal of the American Medical Association, JAMA, ran an insightful article in its March 24/31, 2015 online edition titled "Why Physicians Err in Diagnosis." Among the reasons cited are the following: ignorance, failure to think anatomically, failure to think at all, inherent difficulty of the case, and incomplete examination. It might surprise you to know that the article, though currently running, is in the 'JAMA Revisited' section of the journal; the article was originally published in 1915. Skeptics could argue that perhaps, not that much has changed in the interim.
Additionally, when one leaps the 100 years from 1915 to the present, others reasons, some more technical than others, become apparent as to why physicians "Err in Diagnosis," or miss the diagnosis altogether.
- With over 7,000 known Rare Diseases (most identified after 1915), there is simply not enough time in the medical school curriculum to cover all of the disorders. While most physicians might be familiar with aspects of ALS, MS, or Cystic Fibrosis, how many even know that disorders such as Trismus Pseudocamptodacyl Syndrome or Dysplasia Epiphysealis Hemimelica even exist? Segue into the next point:
- As diseases get more rare, running the continuum from Rare to Ultra-Rare, chances that a physician has come across a particular disorder decreases, lets say exponentially. There are simply no reference points.
- Budget-crunchers have descended upon the medical profession as never before. The ordering of out-of-the-ordinary diagnostic tests by physicians is, in many cases, becoming more and more difficult to "justify."
- Time allotted a physician for each appointment has become shorter and shorter. Less time than ever before is being given to the patient.
- Data-sharing infrastructure up to the present time has been minimal at best in providing physicians and researchers the opportunity to adequately disseminate and share information pertaining to rare diagnoses.
It is estimated by the Institute of Medicine that in the US alone, there are 12 million diagnostic errors annually. The highlighted article addresses nicely the harm to patients when diagnosis of serious illnesses are delayed or missed altogether - ranging from marked deterioration in health and well-being to, yes, many (100,000) deaths annually. How many individuals with rare genetic disorders become "casualties" of these diagnostic errors? Impossible to surmise, but not difficult to assume "more than just a few."
Whether one chooses to subscribe to a "doctor as human and fallible" argument or the argument that the proverbial deck has been stacked against physicians, and as a result, the patient - "Rare Diseases as Needles in Haystacks" - one conclusion is difficult to escape: The traditional system of diagnosis in general, and in the context of this article - Rare Diseases specifically - has been 'disappointing" at best, somewhat of an abject failure at worst. From a personal standpoint I believe most doctors have done the best they can in the face of limited resources and inherent limitations.
Enter the Machines:
Rather than me, a Rare Disease patient, not an expert in the intricacies of genome sequencing, getting into technical aspects of how "The Machines" are transforming diagnosis of genetic disorders, an extremely small sampling of recent articles might serve as a more effective indicator:
100,000 Genomes Project leads to first rare disease diagnoses
Rare disease diagnosis breakthrough
Gene Scan Helps Diagnose Mystery Disorders in Children
Beyond pure diagnosis, sequencing is performing another critical task. It is identifying novel biomarkers for disease detection and possible future treatments and cures. Novel genetic biomarkers for a slew of Rare Diseases, from ALS to Multiple Sclerosis to rare pediatric cancers and on and on, have been revealed in the past few months, markers which would have almost certainly gone undetected without the power of genomics.
The simple, undeniable fact is that sequencing works. It is proving itself on a consistent, almost daily basis and with more compiled data and more effective use of it, things will only get better. Proposals such as the "Internet of DNA," featured in MIT Tech Review, exemplify how "life-saving" genomics-based DNA data can be stored, analyzed, and shared with those who need it to connect diagnostic dots.
On a personal level, I have two Rare Diseases: CVID which has a prevalence of 1 in 25,000 to 50,000, and Sweet's Syndrome with a prevalence of approximately 1 case per-million. The diagnosis of each of my disorders was, in retrospect, delayed by a good 15 to 20 years. The signs and symptoms were ALL present. It was human factors which prevented timely diagnosis: failure to communicate, failure to make referrals to relevant experts and for relevant diagnostic procedures, and back to JAMA, circa 1915, the failure of physicians to look at the big picture, instead, seeing every symptom in a vacuum and as unrelated. Machines, as we are being promised, should not be hindered by such factors.
My "Diagnostic Odysseys" are over. I have my answers. I do not begrudge the medical establishment one iota. On the contrary, I hold it in the highest regard. A vast majority of doctors are hard-working, diligent, immensely caring and compassionate, and vastly overworked. As far as diagnosis of Rare Disease goes, however, doctors have met their match. There is a new way. A new era. In it sick patients will be diagnosed via sequencing in days, perhaps hours, and individuals who have yet to show any signs or symptoms of "hidden diseases" will be diagnosed preemptively.
It is my sincere hope that the "Diagnostic Odyssey" will become a thing of the past. I believe "The Rise of the Machines" gives unbridled hope to future patients seeking one of the most valuable things any Rare Disease patient can ever obtain: definitive answers.