Towards acceptance of new diagnostic methodology

Over the last two decades of the 20^th century the future of diagnostics appeared very bright. By the start of the 21^st century we would be deep into an era of specialized treatments for nearly every disease. This revolution in medical care would be driven by the engine of new diagnostics. Comprehensive tests, powered by the information pouring out of the Human Genome Project and using novel technology, were promised to identify the root cause and best treatment for any disease or disorder. Personalized medicine was about to arrive.

So much for that theory.

Some of those promised tests did appear, but never caught on. Diagnostic companies grew and faded as they tried to commercialize tests leveraging new technologies that clinical laboratories would not adopt or could not use for significant volumes of testing. Legacy reimbursement patterns forced clinical laboratories to stay with older tests which, thanks to a byzantine code stacking system, provided opportunities for higher revenue, even if they didn’t provide additive value to healthcare. New diagnostic platforms came and went as time moved on, unable to break into the market. Targeted therapies arrived, but more as a trickle than the expected flood. The Age of Personalized Medicine arrived slowly.

And the cycle persists.

We are now in the new age of Precision Medicine. In this post-Human Genome Project period the public expects that science knows a great deal about human diseases of all kinds. They expect that long promised pharmacy of specialized treatments to finally be available. It is undeniable that we know more than we did about certain diseases- how diseases develop and spread, how and why different therapies work for some patients and not others and who is truly at risk. We have better treatments and, in many cases, know when and on whom to use them. Yet the promise remains largely unfulfilled. The War on Cancer has morphed into the Cancer Moonshot, yet cancer still haunts every family in some way. Heart disease still kills and diabetes continues to rise. Where is this age that was supposed to rely on diagnostics to identify the what, the who and even, perhaps, the why?

Precision medicine has, in fact, arrived for the pharmaceutical industry, becoming an integral part of nearly all drug development programs and resulting in multiple approved products. Regulatory bodies around the world now view information on specific responding populations as a critical piece of a submission package. From development through approval, new therapies are relying on the precision medicine information provided by diagnostic testing. It thus remains paradoxical, given the impact of diagnostic information, that diagnostic tests routinely lag therapeutics in investment, adoption and reimbursement. When validated and used properly, diagnostic testing could provide much more value than their reimbursement rates would indicate in finding the right therapy for the patient the first time, in addition to being able to flag patients for likely adverse events. So why isn’t diagnostic reimbursement valued more for what it can bring to the appropriate use of therapeutics in maximizing care and cost effectiveness? In an era where sample size is decreasing, why is it that tests providing maximal information are not being universally adopted? Why are the newest Next Generation Sequencing (NGS) platforms yielding vast amounts of information often relegated to low reimbursement and an “oh well, give it a try, we might get lucky” attitude at the bottom of the testing selection funnel? The narrow end of the funnel where a whole host of older, less comprehensive, diagnostics have been tried, repeated and found insufficient, but are frequently still ordered and paid for, whether or not they are actually used in medical management. This delay in receiving clinically relevant information can leave a patient with advanced disease and little remaining to do therapeutically.

It’s not for a lack of trying by the diagnostic community.

New diagnostic technologies are, by and large, the products of well meaning, fertile minds focused on the development of new methods to bring the best of medical care to all. The most scientifically successful of those methods are comprehensive, meet an unmet medical need and could truly help the patients by appropriately stratifying for risk, increasing response rates, decreasing the cost of ineffective therapies and adverse events. If all of that is true, why do the most recent powerhouse technologies sit at the bottom of that diagnostic funnel? The last to be used and the last to be reimbursed.

Is it the economics? Is it the validation of the method? Is it the marketing focus on whiz-bang technology that the physicians should never be expected to understand or care about? Is it the history of diagnostic promises made yet unfulfilled? Is it the pressure for physicians to see more patients each day leaving them unwilling to learn something new requiring a use of time they don’t have? Is it a system that has grown beyond its ability to pay for itself?

Yes.

In my view, the entirety of the problem circles around one topic. Empathy. On everyone’s part. Understanding what technology is needed rather than what would be, arguably but unnecessarily, cool. Does the information provided change the mind of the physician? Does it confirm or refute what the physician already suspects about the patient? Does it guide a treatment choice or is there only one treatment path available? If a test does none of those things it is not worth the effort or to be paid for.

But what about the ideas for a valuable new test or a nascent platform? How do they see the light of day? At this writing there is little incentive to determine full clinical utility of a new technology, as there is no path for return on that investment. There is essentially no reimbursement for experimental tests, no matter how promising. The venture funding landscape, thanks to a flight to better return ratios for therapeutics versus diagnostics and poor diagnostic business models, has become exceptionally rocky. The pressure to produce revenues early in the lifespan of a diagnostic device developer is incompatible with the need for true clinical validation, and unrelenting. The collapse of the hype associated with a Silicon Valley model of diagnostic development only serves to further damage an industry desperately in need of a long-term view and a willingness to see the value in the information. Too much is being left to the “other” parts of the system to pick up the slack without a clear line of sight on what those parts are and how they can be applied to new diagnostic development.

How can this be changed? What will move diagnostics out of the afterthought, taken for granted, status of medical care? The current status leaves investment and reimbursement flat at best and removes incentive for innovation and adoption. It seems to me that there needs to be a renewed emphasis on empathy. What does the practicing, non-ivory tower, physician need? What will make them confident that taking the time to recommend a newer test is worth the effort to fill out that first new and unfamiliar requisition?

Physician use of diagnostics is not and never has been about the technology. No physician, pathologists running labs perhaps excepted, cares about the brand of the thermal cycler or the type of NGS platform being used to generate the results they will read. They have 15min with their first patient, and perhaps 30+ patients waiting after that, followed by hours of work after dinner is over and the kids are in bed to go over results and finish their electronic medical record workload. Those results better mean something to them, make their patient’s life better and help them manage their patient’s care or that will be the last time that requisition is filled out. Understanding their day, their workload, their challenges and how a test might help is second only to making sure the diagnostic being developed is the best it can be.

The healthcare insurance establishment must also play an important part in this future. And they will benefit from it. They should work with the diagnostic developer community to provide clear guidance on an achievable level of validation and clinical utility data required before they will consider reimbursement. A few payer efforts to provide such guidance are good early efforts, but are often seen by the diagnostic community as being talking down to rather than as a collaborator in their efforts, and fail to offer a clear or guaranteed method of securing long-term reimbursement.

Insurers also need to incentivize the diagnostic community to develop tests of clear value to their members and then encourage their in-network healthcare providers to adopt the use of such testing protocols. This can be done through publicly supporting new testing initiatives followed by actual, commercially relevant, reimbursement decisions. Such an effort should be supportive of small developers, private or academic. Concentrating their effort on a handful of mega-developers only serves to perpetuate the lack of truly innovative development often seen in small, creative and nimble organizations. Such support of smaller developers will come at a time when these firms need guidance the most and are the most open to molding their platform to the needs of the healthcare providers. Insurers can improve their efforts by dedicating capable staff to this effort which can reap benefits well beyond the overhead cost of the personnel. Such support will bolster the decisions of angel financiers, venture investment firms and private equity to invest in this future.

Diagnostics are the oft misunderstood adjunct to what is commonly thought to be “real” medicine. Yet, the information provided by clinically useful tests can quite literally mean the difference between time wasted and well spent. Between trendy expenditures and cost-efficiency. Between a lingering, expensive death and an improved quality of life.

It is long past time for the debate to focus on how we can make diagnostic development more fruitful for all of us. The diagnostic, pharmaceutical, insurer and regulatory communities need to change the narrative about diagnostics and how much they matter. Because no one wants to be at the bottom of the funnel hoping something good finally happens.