When an organization like AARP speaks, elders tend to listen. So, it is important for organizations with that much clout to make measured statements about medical issues. The following headline of a recent article in the AARP Bulletin tripped our hype sensors.
Every time we review new diagnostic tests at HealthNewsReview.org, we face criticism from the proponents of testing. I suspect that this post will be no exception. Diagnostic testing is rarely a razor-sharp instrument. Just about all tests have pluses and minuses and can be double-edged swords. Our past experience with PSA screening, which was routinely used for years until evidence showed it was doing more harm than good, should give us all pause when making broad statements about the value of diagnostic testing in all comers.
Let’s take a look at each of these six “game changers” and how “real” the science is that supports them.
“Less guess prostate test”
Prostate cancer is a rather commonly occurring disease. Autopsy studies show that prostate cancer is often found in older men who died from other causes. The incidence of prostate cancer ranges from 5% in men under the age of 30 years to 59% in men over the age of 79 years. Given these findings, a screening test that simply identifies the presence of the disease will likely result in a great deal of over-treatment, since many tumors are not aggressive and will never cause a problem during the man’s lifetime. In reality, not all prostate cancer needs to be treated. But knowing which cancers need treatment and which can be safely monitored is a bit beyond our understanding at the moment. As a result, efforts are underway to identify tests that can delineate aggressive from non-aggressive forms of the disease.
The FDA recently approved two new tests to assist clinicians in screening patients. The first is the ProPSA in conjunction with the Prostate Health Index. In theory, this test helps discern between prostate cancer and other prostate disease in men with slightly elevated PSA and the need for biopsy. The second is the Progensa PSA3 test. This test is intended to be used in men who have a suspicion of prostate cancer based on their PSA level and either a negative digital rectal exam or one or more negative biopsies. Neither of these tests has been proven by the test of time, however.
A number of other tests are available from Clinical Laboratory Improvement Amendments (CLIA)-approved labs. These tests have not been approved by the FDA per se but are approved tests when done by a certified laboratory. The AARP story mentions only the Oncotype DX test, but there’s also Prostarix, the Mi-Prostate Score and the Prostate Core Mitomic Test, to name a few.
Suggesting that the Oncotype DX is a game changer is a stretch. The Oncotype DX test (using a tissue sample from a biopsy) measures the presence of 12 cancer-related genes to calculate a Genomic Prostate Score. That score, along with the National Comprehensive Network Score, improves the ability to discriminate the level of risk of prostate cancer into very low, low, and modified risk. In the most recent validation study (presented at a national meeting of the American Urological Association on May 15), the test “refined patient risk for one in four men,” according to the company that makes it, with the biggest change seen from low risk to very low risk. The test costs about $4,000 and, at least at the moment, is not covered by Medicare.
So, the good news is that we are moving closer to a test or group of tests that may predict which prostate cancers are likely to need treatment and those that perhaps should not. The available data suggests that we are not quite there yet, and that Oncotype DX Prostate is only one of the horses in the race.
“Meds and Genes”
While it may be true that all men (and women) are created equal, equality does not apply with respect to drug metabolism. It is true that your genetic makeup may affect how well you respond to a drug or which toxicities you may experience. It would be nice if we had a simple genetic test to identify if a drug will or will not work or cause side effects.
Warfarin, a blood thinner, is used as an example in the AARP story. Warfarin alters the clotting mechanisms of blood. It is somewhat less than ideal because the difference between the correct amount of interference with the clotting of blood (to prevent blood clots from forming) and major bleeding is small. A blood test called the International Normalized Ratio, or INR, is used to assess the blood’s ability to clot, with a reading of between 2 and 3 considered an ideal level for most patients. Because there is a great deal of variability between patients in how they respond to warfarin, most physicians start with a low dose, and based on the response, adjust the dose upward or downward based on the INR. A gene test does indeed exist to help identify who will need smaller or larger doses as the AARP story suggests. But its clinical utility is still up in the air.
Two studies were published in the New England Journal of Medicine in 2013 comparing the usual approach or adjustment of warfarin dose based on the INR or a genetic mutation algorithm. One study of 455 patients showed that the time to get to the right INR was shorter in the subjects who were dosed using the genetic mutation method (21 days) as compared to the standard method (29 days). There were also fewer bleeding events in the genetic mutation method group. However, in the same edition of the Journal, there was a larger study of 1,015 subjects again comparing the two methods of drug initiation. This larger study looked at the percentage of time that subjects in the INR vs. gene test groups were in the therapeutic range (INR of 2-3) in the first 30 days of treatment. There were no differences in the 30 day outcomes between the two groups.
The accompanying editorial concluded, “… it would appear that, despite the variation in trial design, these trials indicate that this pharmacogenetic testing has either no usefulness in the initial dosing of vitamin K antagonists or, at best, marginal usefulness, given the cost and effort required to perform this testing.”
Hardly a ringing endorsement of the test.
The second of 150 possible examples cited by AARP were antidepressants. In 2007 the Centers for Disease Control sponsored a working group to examine the issue. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group* concluded, “The EGAPP Working Group found no evidence linking testing for CYP450 to clinical outcomes in adults treated with SSRIs.”
This does not mean that these tests are not valuable under some circumstances. Genetic variability is an important consideration in identifying difference in response rates to existing and new drugs, but at the moment their utility lies in the research domain and not in routine clinical practice.
As more of the financial burden of healthcare is shifted from insurers to patients, there is likely to be a shift in where many of us will obtain healthcare services. Laboratory testing is an area that is prime for new entrepreneurs and Theranos, the company profiled by AARP, appears to be leading the way.
The story in AARP only tells only one part of this complex story. The desire of many to take more control of their healthcare provides an interesting backdrop to the Theranos story. In addition to offering services based on a physician or healthcare provider order, Theranos appears to be staking out a claim at the consumer level as well. Many states do not specifically prevent consumers from ordering their own laboratory tests, some expressly forbid it, and a few now expressly allow it. Theranos clearly intends to be the leader in the consumer-centric laboratory market.
For those needle phobic among us, the promise of testing without large blood draws — an advantage emphasized by AARP — is certainly appealing. But I would point out that some of the tests listed on the Theranos website do indeed require a large sample and a needle stick. For those who must pay out of pocket, the prices for tests listed on the Theranos website are a bargain compared with commercial lab or hospital-based laboratory prices. And for those who applaud the “democratization” of healthcare, the ability to decide which tests you might want, have a finger stick to obtain a sample, and pay a rather small amount of money in the process is very appealing. Of course, you would also need to know which test to order, when to have the sample taken, and how to interpret the test results. All of this is possible with an educated consumer, but I have to wonder how many of us are up to the challenge.
Dreading that colonoscopy?
For those of us over age of 50, the specter of a colonoscopy can loom large. The procedure requires not eating for an extended period of time, a complete evacuation of the bowel, travel to a clinic or hospital, intravenous sedation, a couple of hours of recovery, and someone to drive you home. Is it any wonder then than many of us would do almost anything to avoid the ordeal?
The alternative highlighted by AARP is a newly approved camera in a capsule, PillCam Colon 2. The story does note that you still need to undergo what most would consider the most difficult portion of the process — the bowel preparation — and the device is only approved for folks who cannot have a traditional colonoscopy. It also points out that if something is found, you will need to undergo a colonoscopy to deal with it. What it doesn’t say is that based on FDA labeling it is only applicable for about 5% of patients at the moment. Why would the FDA limit the device? It’s simple. In its decision summary, the FDA explains that in a trial of 700 people who underwent both a colonoscopy and use of the PillCam Colon 2, the capsule failed to identify polyps about one-third of the time. And by the way, the PillCam Colon 2 is said to be the size of a vitamin. By my measurement it is about 1/2 inch in diameter (11mm) and almost 1-1/2 inches in length (32mm).
And no discussion on colonoscopy would be complete without a reference to Dave Barry’s hilarious narrative on the topic.
Heart Trouble Ahead?
Just when you thought that it was safe to eat eggs, along comes research suggesting that the bacteria in our gut metabolize carnitine, found in eggs, to produce a substance that could cause heart disease. We are told in no uncertain terms in the AARP article that “those with the highest levels of TMAO…had doubled the risk of death, heart attack and stroke compared to those who had the lowest levels.” My takeaway message is to stop eating eggs. Who wants to double their risk of heart attack? By the way, my personal risk based on the Framingham Risk Calculator is a 10% chance of having an event by age 76 years. My intake of eggs, then, has the potential to increase that risk to 20%. Perhaps I should start working through my bucket list now.
But wait a minute: can this possibly be that definitive? Here’s what Dr. Stanley Hazan, who conducted the research, said in a 2013 interview: “These studies show that measuring blood levels of TMAO could serve as a powerful tool for predicting future cardiovascular risk, even for those without known risk factors. More studies are needed to confirm that TMAO testing, like cholesterol, triglyceride or glucose levels, might help guide physicians in providing individualized nutritional recommendations for preventing cardiovascular disease.” Notice the caveats and careful language that were missing from AARP’s description.
Your Personal ECG
The geek in me loves this idea, and perhaps if I had a heart rhythm abnormality I would be interested in having access to this technology. For some folks, the availability of this low-cost app (less than $100 from Amazon) may be helpful in providing additional information to use in collaboration with their clinician.
But the advice provided is, “…you can simply whip it out at the first sign of light-headedness or heart palpitations and simply rest your fingers on the sensors.” And then what?
Of course, you could make your own diagnosis of the heart rhythm, determine if it is serious, and then do something about it. Pretty straightforward for some. Perhaps not for all. The potential downside is that you (or the app) make an incorrect diagnosis, leading to an unnecessary trip to the emergency room or neglecting what is a real issue.
If applied in the context of an ongoing coordinated program of surveillance, the AliveCor heart monitor could add to the overall care. But coordination is key.
The headline of this AARP story is perhaps unintentionally ironic. “Brave New World” comes from a speech in Shakespeare’s “The Tempest,” but it is also the title of Aldous Huxley’s 1932 novel set in a dystopian, totalitarian future made possible by fascinating technological advances. This story is infatuated with technologies that, like those in Huxley’s novel, have a dark side to them. It does not present the evidence in a way that promotes thoughtful consideration of their use.
As I mentioned earlier, organizations like AARP have a bully pulpit. When the organization speaks, lots of people listen. But what is being said, or in this case being written, needs to be spot on. I don’t think this article comes close.
Harold J. DeMonaco is the Assistant Chief Medical Officer for Care Transitions at the Massachusetts General Hospital.