Examining the changing dynamics of test-and-treat programs.
The conventional wisdom tells us that test-and-treat models improve healthcare, provide faster care, reduce cost and reduce morbidities. But do new medicines lead to development of new lab tests, or do new lab tests drive the development or use of new drugs? In this month’s article, I will explore this issue reflecting on changes in test-and-treat programs in the past few decades. I will also shed light on some lab tests that simply soldier on, seemingly immune to changes in availability of new drugs or newer lab tests.
Let’s quickly review the landscape. Most experts believe that lab tests factor into around 70% of all medical decisions. The data is clear. In 2016, Centers for Medicare and Medicaid Services reported $6.8 billion in lab spend, concentrated in the top 6 tests, which comprised 35% of all lab test spend. These tests were:
1. TSH
2. CBC
3. CMP
4. Lipids
5. Vitamin D
6. Hemoglobin A1C
While total lab spending only accounted for 3% of CMS spend in 2016, lab tests are strongly associated with decreases in death rates for cancer, heart disease, stroke, and upper respiratory illness, all leading causes of death in the United States.
So, we can conclude that test-and treat-programs, in combination with Americans taking a more active role in their health (quitting smoking, eating better, and exercising more), are making a positive impact in health and wellness.
But, how do these trends relate to availability of newer medicines since cancer, autoimmune and arthritis, in particular, have seen major new drug introductions in the past two decades? New more targeted lipid/cholesterol medications are now entering the market and are likely to improve outcomes for heart disease even further. In terms of morbidity and mortality, we are clearly seeing progress.
Let’s look at some examples of how the interaction of new drugs and new tests are improving healthcare. I’ve organized them into a few simple categories:
- Improvements in understanding of the underlying disease process that drive new lab test development;
- Changes in drugs and therapies reducing the use of specific tests;
- New medicines making established tests more relevant;
- And some tests that just continue to be immune to changes in drug development and our understanding of the disease they diagnose.
When causes of disease become clearer, lab markers appear to diagnose and or monitor treatment
Nowhere is this clearer than cancer. Understanding the disease at a molecular level, particularly underlying genetic mutations associated with cancer and how therapies can deal with these changes has dramatically improved the kinds of drugs and therapies being used and also the diagnostic methods to detect and monitor cancer. Better chemotherapy agents and new ways of stimulating the patient’s own immune system are making a difference. Cancer death rates in the U.S. have declined by 27% in the last 25 years, the largest reduction in mortality of any leading cause of death. On the lab front, sophisticated new liquid biopsy tests including detection and quantitation of cell free DNA and circulating tumor DNA are detecting cancer earlier and also being used to monitor response to therapy. On the imaging front, low dose CT scans are being used to find lung cancers earlier when they are more responsive to therapy.
Our awareness of sepsis and how it progresses has dramatically changed in the past few years from its characterization as a “blood infection” to our current understanding of sepsis as an infection that leads to an overwhelming and inappropriate immune system response. Sepsis is the number one cause of death in U.S. hospitals and costs the U.S. healthcare system $24 billion annually. Faster diagnosis coupled with aggressive antibiotic therapy is reducing the mortality rate and reducing post sepsis complications. Lactate, procalcitonin and monocyte distribution width have all helped diagnose sepsis earlier and more confidently.
Heart disease is declining largely due to better health habits combined with lipid tests including cholesterol, HDL, LDL, and triglycerides. While statins have been the mainstay of prescription therapy for many decades, newer drugs target reduction in LDL cholesterol which has been problematic for statins alone. Use of newer lipid markers including Apo A1, Apo B and lipoprotein (a) are increasing, and I expect new markers to emerge in the coming years as we learn more about which lipid fractions are most associated with heart disease.
Upper respiratory infection has been subject to dramatic reductions in deaths due to influenza and pneumonia before the current COVID-19 pandemic. This has largely been fueled by greater use of influenza vaccines and widespread use of specific tests for flu, strep and RSV. Multiple COVID-19 antigen and antibody tests are entering the market. New vaccines are being developed and there is evidence that established vaccines for MMR and flu may confer a level of immunity against COVID-19.
Changes in drugs and therapies seem to be making some established lab tests disappear
Cardiac therapy monitoring frequently involved testing digoxin levels when digoxin was front-line therapy to improve pumping efficiency of the heart. Newer therapies including ACE inhibitors, which reduce resistance in the vascular system, have largely replaced digoxin as front-line therapy. As a result, the use of digoxin testing has declined. The same is true on PT/INR where newer anticoagulant medications have begun replacing warfarin. As a result, PT/INR testing is declining.
Some new drugs are making established tests more relevant
Improvements in drugs to treat arthritis, Lyme disease and autoimmune diseases have made established autoimmune tests including RF, CRP, and others more relevant. These diseases all share several patient signs and symptoms. But, until recently, treatments for both autoimmune and arthritis have been largely ineffective. Newer therapies have emerged and are showing significant improvement.
Finally, there are the tests that never seem to go away
There are some time-honored tests that somehow seem to remain relevant no matter how much drug and diagnostic technology changes. Either they were well ahead of their time or advances in technology have not yet created newer, better solutions. While there have been some improvements in ESR speed, ESR continues as a well-established infection marker. RF, CRP and mono have also undergone some changes in how the tests are done, but the markers continue to be relevant. Test-and-treat models are making headway and continued advancements are forecasted to further reduce morbidity and mortality for the leading causes of death.