"Predisease": A concept whose time has come?
"Predisease": A concept whose time has come?
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At a glance
Underlying preventive medicine or preventive care are measures taken to stave off diseases (or injuries) rather than curing them or treating their symptoms. The term "predisease" has recently entered the medical lexicon and denotes efforts to set criteria that are action points for averting major causes of sickness or death in asymptomatic individuals. Examples include precancerous lesions, increased intraocular pressure (preglaucoma), prehypertension, hyperlipidemia, prediabetes and osteopenia.
While prevention efforts are laudable, controversy rages over how far we should go in diagnosing prediseases. As Welch and colleagues write:
"But the truth is that early diagnosis is a double-edged sword. While it has the potential to help some, it always has a hidden danger: overdiagnosis — the detection of abnormalities that are not destined to ever bother us."1
Others go so far as to label this "disease-mongering." In a recent article, Moynihan et al write:
"There's a lot of money to be made from telling healthy people they're sick. Some forms of medicalising ordinary life may now be better described as disease-mongering: widening the boundaries of treatable illness in order to expand markets for those who sell and deliver treatments. Pharmaceutical companies are actively involved in sponsoring the definition of diseases and promoting them to both prescribers and consumers. The social construction of illness is being replaced by the corporate construction of disease."2
The authors point to a mutually reinforcing "alliance of pharmaceutical manufacturers, doctors, and patients groups [who] use the media to frame conditions as being widespread and severe." They particularly deplore the "seeing of risks as diseases," claiming that "inappropriate medicalisation carries the dangers of unnecessary labeling, poor treatment decisions, iatrogenic illness, and economic waste, as well as the opportunity costs that result when resources are diverted away from treating or preventing more serious disease." They allege that "extensive financial ties with leading researchers, [patient groups,] disease foundations, and advertising campaigns (on both drugs and disease) targeted at doctors" expand the boundaries of disease, to society's detriment.
Are we then engaging in a form of medical hubris? Or worse, commercial promotion under the guise of public health? Contentious issues include:
Medicalization. Extending the definition of disease to comprise millions of additional asymptomatic individuals may create an entire new class of stigmatized "worried well," with consequent emotional, psychological, and even social ramifications (not to mention concomitant iatrogenic side effects). Cynics argue that the concept of predisease can easily be subverted to vastly expand the reach of the pharmaceutical industry; drugs and tests often conveniently supplant more difficult-to-implement, but potentially more efficacious, lifestyle modifications. Do we run the risk of overtreating our patients?
Cost/benefit considerations. Primary disease prevention (preventing illness) is a less clearly cost-effective proposition than secondary prevention (treating the ill). In a country that spends more than twice as much per capita on medical care than comparable industrialized nations, can continuing to enumerate and treat prediseases be sustainable?
What to measure. In an asymptomatic population, diagnostic tests must be relied upon to highlight disease risk. Are the tests we currently rely upon to predict disease the most reliable and cost-effective we can deploy? Who will be the arbiter of what constitutes the "new normal"?
Research design challenges. Because the benefits of intervention in low-risk populations are inherently less clear-cut, they are less easily demonstrable. They require large, expensive, randomized prospective studies to yield statistical validity. Extrapolation from studies demonstrating benefits of pharmaceutical or lifestyle intervention in high-risk populations is logically appealing (e.g., the widespread application of the proven benefits of statin drugs in patients with documented coronary disease to healthy populations with high cholesterol). However, evidence-based literature supporting early intervention in predisease remains scanty.
Fuelling the debate are new signs that the medical profession is disgruntled with escalating imperatives to "do something" for patients. A recent survey of U.S. primary-care clinicians shows that many (48%) believe that their own patients are receiving too much medical care.3 Time constraints, perverse financial incentives, and defensive medicine are felt to be conspiring to put pressure on clinicians to intervene more aggressively than they feel is in their patients' best interests. Reaching for the prescription pad or the test requisition form seems an easier expedient than arduously counseling the patient in lifestyle modification. This contributes significantly to soaring medical costs, iatrogenic complications, and patient dissatisfaction.
A recent medical malpractice case illustrates the dilemma facing clinicians. In a chilling precedent, a nurse practitioner was sued for failing to recommend medication for the predisease hyperlipidemia. With the plaintiff's expert arguing that the patient should have received statins and the defense arguing that there was no evidence that statins in this case were more effective than diet and exercise, the jury found for the plaintiff. (See "Predisease and the Law.") Lest cases like these prompt clinicians to reflexively default to the most aggressive therapy, lawsuits have also been initiated by plaintiff's attorneys alleging precisely the opposite: harm due to side effects caused by unwarranted or indiscriminate use of statins.
The polypill epitomizes the argument for pushing the envelope of disease prevention. In a provocative 2003 article, Wald and Law called for universal prophylaxis for individuals older than age 55 years with a cardiovascular "Polypill" consisting of inexpensive, off-patent drugs: aspirin, a beta blocker, an ACE inhibitor, a diuretic, a statin, and folic acid (to combat elevated homocysteine, an intervention no longer thought to prevent or reverse cardiovascular disease [CVD]).4 Their statistical model predicted a whopping 80% reduction in cardiac risk, with a minimum of side effects.
The proposal ignited a firestorm of criticism. Opponents argued against a "one-size-fits-all" approach and pointed out that with a side effect ratio that Wald and Law acknowledged might be as high as 10% to 15%, intervention in tens of millions of otherwise healthy individuals added up to a perilous gamble. Even the modest proposal that all individuals older than age 55 years take an aspirin a day has been undermined by recent trials which suggest that the significant risk of GI bleeding may exceed potential cardioprotective benefits in low-risk individuals.5