THCB

First, Do Net Harm?

Recently, the US Preventative Services Task Force reiterated its recommendation that women not undergo routine screening for ovarian cancer. This was remarkable, not simply because it was a recommendation against screening, but because the task force was making the recommendation again, and this time even stronger.

The motivation for the recommendation was simple: a review of years’ worth of data indicates that most women are more likely to suffer harm because of false alarms than they are to benefit from early detection. These screenings are a hallmark of population medicine—an archetypal form of medicine that does not attempt to distinguish one individual from another. Moving beyond the ritualistic screening procedures could help reduce the toll of at least $765 billion of wasted health care costs per year.

We already know the common changes in the DNA sequence that identify people who have higher risk of developing ovarian, breast or prostate cancer and most other types of cancer. Consumers can now readily obtain this information via personal genomic companies like 23andMe or Pathway Genomics. But we need to do much more DNA sequencing to find the less common yet even more important variations—those which carry the highest risk of a particular cancer. Such research would be easy to accomplish if it were given top priority and it would likely lead to precision screening. Only a small fraction of individuals would need to have any medical screening. What’s more, it will protect hundreds of thousands of Americans from being unnecessarily harmed each year.

Three of the most common mass screening tests are mammography for breast cancer, prostate specific antigen (PSA) for prostate cancer, and the CA-125 blood test for ovarian cancer. All recent data indicates net harm. Take mammography: for every 2,500 women screened over a ten-year period, only one death is avoided but there are six to eight individuals who are harmed with unnecessary surgery, radiation, chemotherapy or some combination of these misinformed treatments. For every 1,000 men, aged 50 or older, screened for PSA, there are no differences in deaths versus an equally large group of unscreened men. However, 180 screened men have a false positive result and undergo a series of prostate biopsy procedures, with at least twenty having an unnecessary treatment.  Ovarian screening has been shown to produce a 10 percent false-positive rate with five out of every 100 women enduring unnecessary surgery to remove their ovaries.

Screening tests are only one category of population medicine. At least $110 billion per year is spent on useless prescription medications, wasted because physicians treat patients as if everyone’s biology were precisely the same. For example, the three drugs with the largest sales today—Humira, Enbrel, and Remicade—are all used for rheumatoid arthritis and autoimmune disorders and cost nearly $30 billion per year. However, only 40 percent of patients have a response. To date, nothing has been done by the life-science industry to understand why the majority of patients will not derive benefit or to develop alternative treatments for them. Instead, the industry wastes their $18 billion and squanders their hopes.

There are common threads for why we are so slow to let go of population medicine. The current way of doing things is simple—the same tests, the same drugs, the same dose for all Homo sapiens. It makes for solid revenue for hospitals and doctors, who derive unintended benefits from the additional operations, procedures, and radiation treatments provoked by false positives. And ditto for the pharmaceutical and biotech industries whose preferential target, from a marketing and sales perspective, would be all people on the planet.

But we have the tools today to make the switch from population to individualized, precision medicine. Just recently in 1 week the Encyclopedia of DNA Elements group published thirty-five papers in leading medical journals that took our understanding of the genome to new heights.  We already have remarkable data describing incontrovertible interactions between one’s genome and many commonly used drugs, including Plavix for blood clots, interferon for hepatitis C, Tegretol for seizures, statins for heart disease, steroid inhalers for asthma, and many more. But we’re not using the information, and so the warnings about population-based medicine must be sounded again and again.

With all the talk and legislation on health-care reform, hardly a word has been uttered about seizing this opportunity. It isn’t just about new ways to save costs, for which we are certainly desperate enough. It’s about avoiding the harm of mass screening and treatments. The term net benefit has been one used in medical circles for the past few decades, but now we must address net harm—and there is evidence that there is plenty of it going on with the way medicine is practiced today.

It is time for the public to demand a better way forward. When a screening test is ordered, patients should question why and demand the data to justify it. When a medication is prescribed, they should ask about the data for how the drug will interact with their genome. It’s time for the government to seize the opportunity to advance the research with tools that zoom in on each individual’s biology and physiology—be it via the genome or wireless sensors—to promote precision of testing and treatment in the future. And, with its pipeline of new drugs drying up and innovation running on empty, it’s time for the life science industry to markedly narrow its target for drug development.

We are at a unique time in medicine, a veritable inflection point that can transcend mass medicine and bring us to one that takes each individual’s distinct properties into account. There is no such thing as an average human being. But the average medicine that is being practiced today is obsolete and intolerable. How long must we accept mass numbers of individuals experiencing unnecessary harm before deliberate action takes hold?

Eric Topol is chief academic officer at Scripps Health, a professor of genomics at The Scripps Research Institute and the author of The Creative Destruction of Medicine.

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14 replies »

  1. Hi there to every one, as I am truly keen of reading this weblog?s post to be updated daily. It carries fastidious data.

  2. Eric: Just finished your book. Nice and interesting. I am a bit concerned about the unintended consequence of VSCAN devices used for routine evaluation. We all acknowledge the primitive aspect of traditional physical exams and for sure VSCAN will likely pick up more pathology than standard physical exams….however…given the limited back ground in ultrasound of most internists, there is an equal if not greater liklihood of numerous false positives, necessitating full fledged Ultrasound exams, CT and MRI exams simply to assure the internist that the findings were innocuous….Such a spin off of testing is just what we do not need (you documented the cost, radiation exposure etc in your book)…any studies on the accuracy of internists with special training in its use? The false negative and positive findings on entirely routine asymptomatic patients??

  3. You are correct about the drug interactions, especially statins, which are very harmful and provide no benefit. However, big pharma will work hard to stop anyone from changing the current situation.
    In terms of screenings, all I can say is, when it’s your cancer, and you weren’t screened, let’s see if you feel the same way.

  4. THCB should have preceded this by a paragraph indicating Dr. Topol’s financial interest in getting people to have DNA testing at public expense. At a time when many conservatives keep pitching “patient centered health care”, i.e. trust the patient to decide how to spend public funds, we have massive propaganda about medical issues and profound medical ignorance by many physicians who figure that it’s easiest if they just order what the patient wants.

    It’s schizophrenic to push for extensive genomic screening as the solution to the problems of other “clumsy screening” such as mammography & PSA testing. Life expectancy for whites with less than high school graduation is falling, women more than men. There’s little obesity in the International Departure Lounge for flights to Europe and Asia. If we want better health for the underprivileged, we must start in elementary school, promote exercise and stop letting the meat packers, agribusiness, coal, oil and gas industries control our school curricula. Do we physicians work for the public good or for the profiteers?

  5. I wouldn’t say shocking, rather amusing.

    And by the way, I have nothing against him obtaining funding if his projects are worthwhile, but I don’t think that blogposts are particularly effective.

    I also don’t know what ETs (considerable) accomplishments have to do with anything I wrote. If you want to write: if someone as smart as ET is obsessed with wireless sensors, there must be something to it, fine. But arguments should stand on their own, and he still could make a better and more realistic case. Just writing that everyone’s genome should be sequenced and as much physiology as possible caught by wireless sensors is not enough, IMHO.

  6. Not sure what you disagree with – I wrote that there does not appear to be much actionable data … who knows, maybe there is some change coming. This is all in the realms of ordinary medical progress (i.e. research/grants, papers, commercial applications, changing practice, guidelines etc.)

    Obsession: Read the other post I linked to. IMHO, there can be little doubt that ET likes the thought of putting probes into human beings. There is nothing new to that (implantable loop recorders/holter, esophagoeal pH monitoring, ambulatory EEG) except maybe for his emphasis of the wireless part, but ET apparently expects some magic from doing much mor of that. I think it’s gizmo obsession. Where physiology data is needed, specialists will push for data collection.

  7. Before slamming ET for being “obsessed” with wireless sensors and questioning his agenda, you should probably consider his contributions.

    http://en.wikipedia.org/wiki/Eric_Topol

    A cardiologist obsessed with wireless technology?

    How completely and utterly shocking.

    A researcher looking for funding?

    What are you obsessed with? Anything?

    Eric J. Topol, M.D. is an American cardiologist, geneticist, and researcher. Much of Topol’s career was spent at the Cleveland Clinic, where he served as chairman of cardiovascular medicine and founded the Cleveland Clinic Lerner College of Medicine. Topol was one of the first researchers to question the cardiovascular safety of rofecoxib (Vioxx),[1] culminating in the drug’s ultimate withdrawal from the market. Topol’s advocacy on the subject led to what the New York Times described as an “unusually public dispute” with the Cleveland Clinic’s leadership over ties between the academic institution and the pharmaceutical industry, ultimately leading to Topol’s departure from the Clinic after his academic position was abolished.[2][3]

  8. @rbaer, I appreciate the cynicism, but I don’t think he’s being obsessive or biased. The points around individualizing population statistics and medicine are actually very fair and interesting ones. The problem is that they are largely irrelevant currently in the day-to-day practice of medicine. How many people really walk in with a fully sequenced 23andme genome??

    The government is trying to get their hands around some very rudimentary cost, quality and access issues. While individualized medicine is going to certainly improve how we can tailor care (and yes, this will impact cost, quality and access), it won’t happen for some time. The issues we are facing currently are too critical (ie medicare funds being run through in the next 30yrs) to wait for the wider acceptance of sequencing and technology.

  9. “why are we defining “quality” as a bunch of population based screenings?”

    Because it’s easy and “we” can?

    (Of course, the word “easy” is relative. I have one insurer that regularly dings me for not ordering PSAs on two female patients in their 80s)

  10. “But we have the tools today to make the switch from population to individualized, precision medicine. Just recently in 1 week the Encyclopedia of DNA Elements group published thirty-five papers in leading medical journals that took our understanding of the genome to new heights. We already have remarkable data describing incontrovertible interactions between one’s genome and many commonly used drugs, including Plavix for blood clots, interferon for hepatitis C, Tegretol for seizures, statins for heart disease, steroid inhalers for asthma, and many more. But we’re not using the information, and so the warnings about population-based medicine must be sounded again and again.”

    This is just silly. “thirty-five papers in leading medical journals that took our understanding of the genome to new heights” does not automatically result in actionable data.

    Medicine is and always has been about the most individualized treatment possible. The medical literature is full of articles better defining existing conditions based on a variety of factors, including symptoms, family history, risk factors, tissue samples … in fact, a lot if not most current medical research is basically geared towards defining, understanding, diagnosing and treating diagnostic subcategories. That’s why page numbers of diagnostic criteria and medical textbooks are growing so much.

    Now, if there is clear evidence that patients with a certain gene will significantly benefit from a different treatment, that approach – testing and treatment modification – will prevail. If evidence is murky or the benefit is marginal, it will not. It is a s simple as that.

    “It’s time for the government to seize the opportunity to advance the research with tools that zoom in on each individual’s biology and physiology—be it via the genome or wireless sensors—to promote precision of testing and treatment in the future.”

    2 things come to mind after reading this sentence:
    (1) ET wants government money – I hope he is also writing grant applications.
    (2) After reading previous articles (e.g. https://thehealthcareblog.com/blog/2011/12/26/digitizing-human-beings/), one cannot help but wonder whether ET is obsessed with wireless sensors.

  11. Trying to summarize problem that seems at many levels.
    1. Biopsy are sampling exercises. They may not capture malignancy or capture it late for some folks.

    2. Then there are false signals leading to treatment not needed. Doesn’t seem logical. I would assume there would be multiple tests to confirm malignancy before starting treatment.

    3. Even when correctly identified, there are treatments prescibed that are not effective. Once again seems strange though not suprising. One would assume physicians use their experience to determine efficacy during prescription. Then these medicines also pass through FDA evaluation. Are these evaluation not effective? Evidence based medicines evidently doesn’t do well on numbers.

    4. Then are side effects of medicinces prescribed correctly.

    There does seem to be some genetics tilt in the article. Then of course is conveyor belt industry aka population medicine. Of course we all know it is most economical way of operating given payment models in place. The other part that I would like to point out to Margalit’s point is that providers have also learnt to marry quality with economy. That quality is of course defined in terms of heart attacks, BP, cholestrol and all those vitals of individual health. Kaiser is particularly good with that. But I find this quality driven healthcare disturbing. Aspirin and statins, based on Kaiser brochures seem to be part of preventive menu. Many of these medicinces are symptom killers. The symptoms are delayed or distorted. Malfunctioning liver may not be on vitals list or a liver that goes kaput five years down the lane would not show up on results.

    That said, industry has been conveyor belt for long time and I don’t have better answers. Industry is there to earn profits and it will continue to find ways to do that. The most pertinent question as is asked above, why are patients not asking questions. I really love the statement that patient ask doctor for data showing that it works and goes to fundamental questions who stands for patients?

  12. If that’s the case, why are we defining “quality” as a bunch of population based screenings, as in the Weill Cornell study that “proves” (based on 2008 data!) that EHRs improve “quality” of care because docs with EHRs ordered more screenings for breast cancer, chlamydia, colorectal cancer and A1c (thrown in there for good measure)?
    Is “quality” independent on “net harm”?

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