According to 2010-2012 data from the National Cancer Institute (NCI), 40% of men and women will be diagnosed with cancer in their lifetime. In all its forms, cancer is known to be a clinically and emotionally challenging disease to manage. Despite the fact that each year 455 men and women per 100,000 patients are diagnosed with cancer (NCI, 2008-2012 data), 1 in 5 cancer patients are still misdiagnosed, further exacerbating the challenges of treatment for clinicians, patients, and their families.
Founded in 2011, Precipio Diagnostics out of New Haven, Connecticut is a reference laboratory using advanced diagnostics and personalized medicine to reduce the prevalence of cancer misdiagnosis. Today, Precipio reports a 99% accuracy rate in correctly diagnosing cancer patients through the company’s unique combination of offerings.
Precipio’s diagnostic services include laboratory testing and clinical review through partnerships with some of the nation’s leading medical institutions, including the Yale School of Medicine. In addition to its services, Precipio is also developing and commercializing products in line with its diagnostic services. Last month, the company filed a provisional patent for a non-invasive cell capture device for gynecological cancer detection.
To learn more about Precipio’s offerings and vision for improving cancer diagnosis, Medgadget had a chance to speak with the company’s Founder and CEO, Ilan Danieli.
Michael Batista, Medgadget: What are the causes of cancer misdiagnosis and what are the repercussions when a patient is misdiagnosed?
Ilan Danieli: There are many reasons a patient can be misdiagnosed; we believe one of the key causes of misdiagnosis is the lack of subspecialized expertise of the diagnosing pathologist. As the complexity of cancer continues to increase, the ability to correctly diagnose a patient is largely driven by the pathologist’s experience and focus. Pathology is largely a matter of pattern recognition; experience and expertise in being able to review the various components of the case (biopsy slides, clinical information, patient history); and putting together the picture to arrive at the right diagnosis. This requires significant training and the development of subspecialist expertise. Conversely, we see the pathology industry moving in the opposite direction, with pathologists functioning more as generalists, being asked to do more, review a broader range of patient types, with less training.
The repercussions of misdiagnosis can be lethal. The diagnosis sets the path for the entire treatment course the patient and their oncologist will embark on as they begin their battle against the cancer. A wrong diagnosis will send even the best and brightest of oncologists down the wrong path. To be clear, when we say misdiagnosis, the bulk of the mistakes are incorrect classification of the disease. A false positive/negative is less frequent, although sadly, it does happen, and we have seen many such cases. Misdiagnosis can result in placing the patient on the wrong treatment, which can lead to disease progression and further harm to the patient. It’s important to keep in mind that cancer treatment involves chemotherapy, which uses highly toxic drugs that are put into the patient’s body with the intent of attacking the cancer cells. With various treatments designed to attack different types of cells, administering the wrong chemotherapy drug can be catastrophic.
Another element of the diagnostic process is determining the prognosis (severity) of the disease. Many cancers are defined both by stage, as well as how aggressive they are. Less-aggressive cancers are treated in a different manner than more-aggressive cancers; the decision on how aggressively to treat the patient is based on the pathologist’s determination of the disease prognosis.
Medgadget: What are the industry standards for diagnosing cancer today which lead to these surprisingly high misdiagnosis rates?
Danieli: It’s important to understand that the diagnostic process includes two elements. The first is the laboratory work, often referred to as the “technical component,” where the biopsy is received and various tests are run on it. This includes chemical staining, laser-based analysis, chromosome evaluation, and many other tests. The industry standards are governed by Clinical Laboratory Improvement Amendments (CLIA), which mandate the method in which a laboratory test is developed and validated, and the ability to reproduce consistent results. While there are guidelines in terms of which tests are customarily ordered based on the clinical information and the type of biopsy, these tests are laboratory-developed (termed LDTs) and each laboratory may have different protocols for which tests are run and how they are set up. Many of the characteristics of the laboratory output are also driven by the medical director’s preferences and expertise. These factors can result in various degrees of variability in the output a laboratory produces.
The second element of the diagnostic process is the professional interpretation. In this step, the pathologist receives all the laboratory “outputs,” reviews all the information, and arrives at a diagnosis. The ability to arrive at the correct diagnosis is largely driven by the pathologist’s training, experience and expertise. If the pattern presenting in the slides and other materials is familiar to the pathologist, either through training or having seen it before, then there is a higher likelihood that they will arrive at the correct diagnosis. In order to qualify to render a diagnosis, the physician must be a board-certified pathologist. However, while there are many subspecialist certifications that provide a higher level of training and subspecialized expertise, there is no regulatory requirement for pathologists to complete these subspecialized training programs in order to diagnose such cases.
For example, we specialize in hematopathology (cancers of the blood system: leukemia, lymphoma, etc.), one of the most complex types of cancers to diagnose. While there is a board certification as a subspecialist hematopathologist, many pathologists with an anatomic pathology certification, who don’t have that board certification, still diagnose blood-related cancers.
Medgadget: Why did you and your team at Precipio think you could improve upon the industry standards?
Danieli: We observed a growing gap between the need for subspecialized expertise required to reach the correct diagnosis and what the industry was providing. We recognized that one of the only sources of subspecialized expertise was within premier academic institutions; however, the only patients who were benefitting from that expertise, <5% of the patients in the US, were those who were fortunate to live close to and be treated in a leading academic institution. We realized that if we could build a platform that harnessed that expertise and made it accessible to patients outside those academic institutions, we could provide a higher level of care to those patients by ensuring that the most important step in the battle against cancer—the diagnosis—was done right.
Medgadget: Precipio’s offerings include a combination of services and products. Let’s start with the services. Can you tell us a little more about how Precipio’s services such as SmartPath and SmartGen work?
Danieli: Our vision is to provide any patient, wherever they are, with access to the most accurate diagnosis. This involves access to both the best technologies in the laboratory, as well as access to the best-trained pathologist to ensure the correct diagnosis is provided. SmartGen™ and SmartPath™ provide both of these tools.
As we all are aware, genetics are becoming a key driver in identifying features of the tumor that can lead to individualized, precision treatment based on the patient’s personal genetic characteristics. SmartGen™ offers patients access to academic-based genetic tests that are developed by the researchers in some of the world’s leading cancer research institutions. This includes advanced diagnostic tests that both utilize the most cutting-edge technologies as well as incorporate the evaluation of the latest set of genes known to be associated with various cancers. This means that if a patient has a genetic mutation that may indicate a certain treatment path, these tests will likely find it.
SmartPath™ provides access to the second critical element of arriving at the correct diagnosis—access to an expert pathologist. We are building the world’s largest network of academic expert, subspecialist pathologists who will provide their expert opinion in reviewing the patient case materials and arriving at a diagnosis. Unfortunately, since we launched this service, we have overturned numerous diagnoses that we believe would have set the patient down the wrong path; some received a second opinion after commencing a treatment course that turned out to be the wrong one. Our service includes a full, comprehensive review of the materials initially generated by the primary diagnosing laboratory by an expert pathologist. Upon receipt of the case, we will triage it and assign it to the subspecialist expert within our network, to ensure that the patient and their biopsy are paired to the correct academic expert.
Medgadget: What about Precipio’s products?
Danieli: Through our recent acquisition of Transgenomic, we have developed ICE-COLD PCR (or ICP), which is our liquid biopsy technology. Prior to the emergence of the liquid biopsy, clinicians relied solely on the genetic information obtained from the biopsy of the tumor taken during disease onset. It’s rare that the patient is re-biopsied beyond that; this results in treatments administered that, absent updated genetic information, may become ineffective and perhaps even harmful.
We now know that tumors shed fragments of DNA in the bloodstream, called circulating tumor DNA. The ability to target those DNA fragments within a blood sample and enable genetic analysis, changes the way a patient’s disease progression and specifically the tumor’s genetic footprint can be monitored. Liquid biopsies are transforming cancer treatment by enabling a minimally invasive blood draw that provides a wealth of real-time, comprehensive information on the biology of the tumor itself. Clinicians no longer have to rely on outdated information from a biopsy that was taken one, two, or even five years prior. They now have current information they can act on.
Our technology enables any laboratory conducting genetic cancer testing on tissue (solid tumors) to easily, quickly, and at no incremental cost, expand their diagnostic capabilities to conduct the same genetic testing on blood samples. Furthermore, because our technology resides in a chemical and does not require any additional equipment purchased, it is affordable, easy to incorporate into the work flow, and, equally important, laboratories can stay competitive by increasing their offerings.
Medgadget: Precipio facilitates an academic research collaboration between clinicians and researchers. How does this collaboration benefit each side of the equation and what is the role of this collaboration in Precipio’s model?
Danieli: Academics conducting research are constantly in search of patient samples in order to broaden the scope and breadth of their research and further validate their discovery. Patient samples are hard to come by and are oftentimes sources from a certain geographic region, thus limiting the diversity of those samples.
Clinicians and their patients, on the other hand, are the ultimate recipients of the fruits of any research that is conducted at those academic institutions. Therefore, they have a vested interest in contributing to those studies with the hope that one day, as has happened numerous times in the past, those studies will yield medical advances that will benefit them and other patients.
Precipio facilitates that collaboration by pairing clinicians and their patients, particularly those with their diverse disease states, with academic researchers who are seeking these patient samples in order to further their research.
Medgadget: Did Precipio originally set out to be both a service and a product business, or did that strategy evolve over time as a result of market trends or needs?
Danieli: Our overall vision was always to eradicate the problem of misdiagnosis. The primary tool we believe our platform delivered was access to academic-level expert pathologists; this resulted in creating the pathology services business. However, there is no doubt that technology plays a role in arriving at a correct diagnosis, and so over time, our business evolved to begin to look at various technologies that we could incorporate into our offering. Over the past few years, we have both developed technologies in-house, such as IV-Cell and Juno, as well as acquired technologies such as ICP.
Medgadget: How do different types of stakeholders [i.e. patients, providers, payers] derive value from Precipio’s services and products?
Danieli: All three stakeholders gain substantially from Precipio’s services providing an accurate diagnosis. The value to the patient in getting the correct diagnosis is obvious and needs no further explanation. Same for the physician, having the support of and access to an expert, subspecialized pathologist they can consult with on a specific case, is priceless in terms of formulating the correct plan of attack for the disease.
Payers play an enormous role in this process and stand to gain significantly from our services; unfortunately, the system is complex so they are also difficult to approach and can take longer to accept change. The cost of treating a cancer patient ranges from $100,000 to $250,000 depending on the type and severity of the disease. This often involves chemotherapy and other treatments that are extremely expensive and are paid for by the payers, the insurance companies. Administering the wrong treatment to the patient as a result of misdiagnosis is not only a waste of resources; it can also have downstream effects in causing the patient more harm than good, resulting in further disease progression as well as other potential ailments, which all translate into additional costs borne by the payer. Arriving at the right diagnosis ensures that the payer’s resources are correctly applied to the patient’s situation to ensure the best outcome.
Medgadget: Can you share a little about Precipio’s business model? Are your offerings covered by health insurers or would a patient need to pay out of pocket?
Danieli: All of our tests and services are based on industry-accepted guidelines and corresponding CPT codes, and are fully recognized by insurance companies. Precipio is an approved Medicare provider and we are in-network with hundreds of insurance plans that routinely reimburse for our services. Insured patients will not incur any additional out-of-pocket costs other than their standard co-pays and deductibles.
Ultimately, we believe that as insurance companies transition from fee-for-service to value-based payment, it will become clear that the value proposition Precipio provides in terms of delivering an accurate diagnosis results in not only patient improvement but also a substantial economic impact.
Medgadget: For any disease condition, diagnosis is the first step. How does Precipio think about or play a role in the either the transition to, or next steps of, mitigation and, if possible, recovery following diagnosis?
Danieli: As a diagnostic company, we are tasked with providing information to help guide the treating physician, in cancer, the oncologist, in taking care of the patient. Therefore, our key focus is on the first, and, we believe, the most crucial step, in getting the diagnosis right. Having said that, ICP, our liquid biopsy technology, enables monitoring of the patient as they go through treatment. We now know that during the course of treatment, the genetics and biology of the tumor often change, sometimes as a result of treatment. Once these changes occur, the existing treatment may no longer be effective. ICP allows physicians to conduct repeat testing to monitor the patient’s genetics and provide a real-time picture of the current patient’s genetic profile, allowing for the adaptation of treatment to the patient’s individual genetic characteristics. This is the true revolution of precision medicine, and we are excited to play a role in this field.
Link: Precipio Diagnostics…