Comparative Effectiveness Research

Physicians are not likely to admit and patients would not be happy to learn that much done in the practice of medicine is based on little more than custom.  Historically, the absence of well designed, statistically sound, randomized, clinical trials - RCTs - has not discouraged the introduction and use of ineffective, costly treatments with significant risks and complications.  The status quo plays a large role in the reluctance to question let alone abandon established practices even though we can no longer afford the costs associated with untested and unproven treatments of questionable efficacy.
         
Recently, a move to promote what has come to be known as evidence based medicine has changed the process of examining and testing new therapies before clinical approval and adoption.  Many believe the best opportunity to reduce the rate of increase in the cost of medical care is comparative effectiveness research - CER http://www.effectivehealthcare.ahrq.gov/index.cfm/what-is-comparative-effectiveness-research1/  CER involves rigorously designed RCTs to evaluate contrasting approaches to the treatment of a specific condition with the goal of identifying the best among them based on objective measurable indices.
       
While CER can't guarantee definitive, accurate conclusions about the effectiveness of a given treatment regimen, without such studies it is not possible where there are alternatives to justify the use of one rather than another.  The current need to control the costs of medical care demands that even medical procedures currently accepted as the standard of care must be validated by well designed RCTs.  The fiscal environment will result in payers demanding that all therapeutic regimens be proven to be effective before judging them eligible for reimbursement.
         
Studies have recently been initiated to evaluate established practices adopted without such substantial proof of effectiveness.  Regrettably, many after being subjected to greater scrutiny have been found to be not as effective as originally thought.
         
The Affordable Care Act - known as Obamacare - has many mechanisms that could, if appropriately implemented, have the effect of limiting practices to those that are supported by CER.  This will encourage CER and represents the potential for substantial savings.  There are legitimate concerns about just how these issues will be identified and implemented and the text of the legislation leaves some questions about exactly how this goal could be achieved. The recognition that better effective procedures justified on a cost benefit basis demands the evaluation of treatments, tests, technologies, systems of care delivery all coordinated with payment policies.  This involves redesigning many current practices with regard to reimbursement.  
         
The adoption of CER represents a significant change in the current culture of clinical medicine.  Clinicians, administrative officers, and payers will have to be willing participants and accept changes.  This will only happen if patients are educated to demand care that has been proven to be effective and the best management for their condition.  Absent these changes in our approach to the identification of best practices, the cost projections of the ACA cannot be achieved.
         
It is a fact and may come as an unpleasant surprise that there are large differences in the outcomes of treatment for many diseases that are difficult, if not impossible, to explain.  Simply acknowledging these differences exist is both helpful and useful in pursuing the best of alternatives.  Of course, without the assessment of the data pertaining to critical clinical decisions, including the individual preferences for treatment of the physician, decisions about the appropriateness of treatment options and evaluation of outcomes is not possible.  Ultimately, treatment decisions are made by patients, relying predominantly on the judgment of their physician, and perhaps secondarily influenced by the policies of their insurance carrier who in many cases is a surrogate for their employer who has chosen to provide a given medical care benefit structure.   In the final analysis, the information that the patient needs to make an informed decision is most frequently obtained from the physician whose responsibility it is to present treatment options, their risks and benefits.  Patients then can consider their options in the context of their preferences in selecting any procedure from diagnosis to treatment.
         
CER is not an academic issue.  It is brought into sharp focus where a condition can be managed by any number of currently acceptable therapeutic options. This is the case for many common diseases including prostate and breast cancer, coronary artery disease and stroke.  Patients should explore the available data with their physician when a choice is to be made among alternatives.

Million Hearts Program and The New York Blood Center

Cardiovascular disease is the leading cause of death in the United States.  Two million Americans have a heart attack or stroke every year and more than 800,000 of them die.   The economic affect of these events is estimated to exceed $450 billion annually.  A recent initiative to reduce these events, Million Hearts, is a joint venture involving governmental agencies together with private sector partners.

This effort will focus on the management of the ABCDS of heart disease - Aspirin for high risk patients -  Blood pressure control - Cholesterol management - Diabetes -  Smoking cessation.  Management of these factors has more potential to prevent deaths and reduce morbidity than any other prevention program.  Less than half of the individuals with hypertension who are being treated have it adequately controlled.  The definition of hypertension has been refined and new limits for what is now considered prehypertension have been established. A review of recent studies suggests that young and middle-aged people with slightly elevated blood pressure, or prehypertension, are at much greater risk of stroke than those whose blood pressure is in the normal range.  People under age 65 with prehypertension had a 68% increased risk of stroke compared with those with normal readings, independent of other known risk factors.  Only a third of those with high cholesterol levels are receiving proper treatment.  Fewer than half the individuals with pre and early diabetes are aware of it.    

The increasing prevalence of obesity and diabetes demand that we attend to these identifiable and correctable issues in order to control the incidence of heart disease and stroke. The American College of Cardiology, American Heart Association and American Medical Association have established specific goals for treatment that may require patients to take one or more antihypertensive medications to achieve the desired blood pressure readings.  Control of low-density lipoprotein cholesterol (LDL-C) to levels below 100mg/dl has been identified as a central issue in the management of high blood pressure.  To achieve this a prescription for a statin drug is indicated.  Stopping smoking is another goal of treatment of the patient with hypertension. 

The Affordable Care Act (ACA) provides a foundation for the Million Hearts' project by increasing coverage and facilitating improved care.  It waives patient cost sharing or insurance copays for preventive services, including blood-pressure and cholesterol screening and smoking-cessation counseling and treatment, for enrollees in new private insurance plans.  While cost is a significant factor in establishing most preventive medical programs, the biggest hurdle for all efforts to identify those at risk of untoward events is the identification of those individuals for whom treatment is both possible and appropriate.  For many conditions, population wide screening to identify those with important risk factors is not cost effective.  


The New York Blood Center, NYBC, a community based, nonprofit, independent organization, is the central blood collection facility that provides blood components to 200 area hospitals serving more than 20 million people.  With approximately 2000 blood donors a day being processed at the blood center's facilities, it has designed and implemented an extensive donor screening program for abnormal levels of cholesterol, blood sugar and blood pressure.  The NYBC's Cardiovascular Disease Risk Assessment and Prevention Program is a demonstration project providing free screening, risk assessment, education, and referral of at-risk persons for further evaluation and treatment.  The program is intended to advance cardiovascular disease prevention, motivate lifestyle changes, and ultimately improve the health of the people who provide blood donations each year to the NYBC.  This screening program is integrated into their blood collection routines.  The efficiencies of this program make it an appealing template for the identification of those at risk who would benefit from medical intervention to reduce their risk of heart disease and stroke. 

Effective preventive medicine strategies rest on the identification and mobilization of efficient methods to capture the appropriate at risk populations.  Only by employing the practices, procedures and processes of independent ancillary health organizations such as the New York Blood Center will it be possible to achieve the ambitious goals of the Million Hearts program.     
 

Medical Practice and Government Regulation

In July, the Food and Drug Administration issued a warning about serious complications associated with the use of surgical mesh in gynecological surgical procedures. Based on 1,500 reported complications between 2008 and 2010, the letter advised surgeons to consider the risks of using mesh and recommended that patients be fully informed of potential complications.  The mesh was approved for use 10 years ago and has been placed in thousands of women.  Complications include perforation of the intestine, hemorrhage and death.  Still more disconcerting, the FDA warning points out it is not clear that surgery with surgical mesh is any more effective than alternative procedures without mesh; and use of it may expose patients to greater risks, including impairment of quality of life and the possibility for multiple surgeries to remove it.  Furthermore, they warn it may not be possible to remove the mesh entirely and complications may never be completely resolved.

The FDA summarizes the adverse events reported through its Manufacturer and User Device Experience data base as well as from peer reviewed literature.  This warning ends with the recognition that rigorous comparative effectiveness research is now essential to prove product safety and efficacy    http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm262435.htm.

It was as a result of a spate of public health disasters associated with a few new drugs and medical devices in the 1970s that public attention was focused on the potential for these kinds of problems.  At that time, laws were passed to protect the public.  In the 1990s Congress enacted additional regulations to the original statutes.

This is hard to believe but the standard for approval of medical devices is safety and effectiveness, which is interpreted to mean a new device is equivalent to a previously approved device. The implicit assumption is if a new device is equivalent to a previously approved similar device, it will be as safe and effective as that one.  Recently, on several occasions, the FDA and the courts disagreed with that assumption which is at the very least confusing.  However, we have a system in which a new device can enter the market because it is substantially equivalent to another device that may have been approved only because (again) its manufacturer showed it was substantially equivalent to yet another previously approved device.  This could and may already have resulted in a cascade of approvals going back to devices that might never have been assessed for safety or effectiveness.  To top it off, a new device without any single product to which it is similar can be cleared by having various characteristics that are equivalent to individual traits of two, three or more different previously cleared devices and those devices do not even have to have been marketed!  In this case, there may be no real-world experience to provide a basis for assessing safety or effectiveness.

Recently, a committee of the FDA decided this house of cards should be replaced with an integrated, pre-marketing and post-marketing regulatory process where a data base is created to permit ongoing evaluation of the safety and effectiveness of a device.  The experience with the use of surgical mesh in gyn surgery demonstrates that the only hope for capturing the information needed to maximize the likelihood of uncovering significant risk of serious complications quickly is rigorous post-marketing surveillance.  The realization that such a program is sorely needed for all devices and drugs led the FDA to establish the new Risk Evaluation and Mitigation Strategies, REMS.

Recognizing that 90% of adverse drug reactions go unreported and that such events reported by physicians is the primary way drug safety is monitored in the U.S. by the FDA, the Physicians Desk Reference network which is an organization that is a link between physicians and drug manufacturers has established a mechanism to report such events that is a simple, free online service for reporting adverse drug events https://www.rxevent.org.

As a reaction to the thousands of lives damaged or ended and billions of dollars spent as a result of widely used, unproven methods and with the acknowledgment that so much of medicine is based on subjective and highly idiosyncratic interpretations of treatment responses, the journal Evidence-Based Medicine http://ebm.bmj.com was founded in 1995 as part of the British Medical Journal group.  Evidence-Based Medicine systematically searches a wide range of  medical journals applying strict criteria for the validity of research.  Experts critically review the most clinically relevant articles and summarize them including commentary on their clinical applicability.

Effective regulation is in its infancy.

Clinical Medicine, Capitalism and Creative Destruction

As the second world war ended, The Great Atlantic and Pacific Tea Company was opening supermarkets all over the country.  In time, local neighborhood grocery stores, bakeries and meat markets disappeared. When WalMart, Kmart and Target saw the opportunity, they began to compete for the family food dollar and eclipsed the A&P.  At the same time, small family farms were absorbed by large produce packaging companies.  They amassed huge tracts of land and adopted industrial scale methods of production.  Frank Perdue became a celebrity.


After that war, the automobile became a global product.  Newly established brands from Europe and Japan entered the American market.  Ford, General Motors and Chrysler survived and lesser marques like Nash, Hudson, Packard and Studebaker went the way of the corner grocer.  Lee Iacocca became a celebrity.


These are examples of the concept characterized as creative destruction.  It was inevitable that this model for change would come to the practice of medicine.  Over the last 20 years, the cottage industry of clinical medicine has been transformed into a collection of corporate behemoths.  In the process, Drs. Gupta, Chopra and Oz have become celebrities.


UnitedHealth Group Incorporated recently acquired the operations of a major physician's organization in California.  The purchase of the management arm of an association of approximately 2,300 physicians in a range of specialties established UnitedHealth's Optum Health Services platform as a formidable presence in the region.  Optum had previously taken over two smaller groups in southern California - AppleCare Medical Group and Memorial HealthCare.  This is the latest example of how lines are blurring between insurance companies and health care providers.


There is no way anyone could confuse the operating principles of such large corporate organizations with the insignia of the single practitioner or small groups of practicing physicians. The days are gone when a physician could move to a community, open an office, hire staff, and build a practice.  It is much too complicated today.  New legislation requires expensive technology, electronic medical records and structured human resources.  In order to deal with all the new rules and regulations, an affiliation with a large management organization is practically mandatory.  All over the country, individual physicians and groups are signing up with area hospitals, medical centers and academic teaching institutions.  As they recruit and buy practices, these large, multimillion dollar institutions with multibillion dollar budgets have made it possible for physicians to affiliate without having to move their office, change their staff or even change their telephone number.


These changes have not escaped the attention of doctors.  When I was in training, it was understood that a physician in practice had to deal with the demands of running a small business.  Although these issues were never mentioned in medical school or during house staff training, I knew there would be some relationship between my overhead costs and take home pay.  As more and more physicians realized that they weren't going to be just practicing medicine but would be part of a health care industry, they decided a Master of Business Administration degree was the appropriate credential.  By the late 1990s, there were a half dozen joint MD/MBA degree programs in the country.  Today, 65 institutions offer the combined degree program - with tuition and fees amounting to more than $250,000.  Not a trivial investment!  And, more significantly, not time spent acquiring or mastering skills sets relevant to caring for the sick!


Perhaps the most striking feature of the corporatizing of medicine is the widespread use of advertising campaigns by doctors and hospitals in newspapers, magazines and on television with the objective of increasing their market share.  It's not possible to estimate the total spent for advertising, however, it is clearly a significant addition to the cost of business.  Prestigious institutions such as New York Presbyterian, Johns Hopkins, Baylor, Cleveland Clinic and Cedars-Sinai have all launched costly promotions to extend their brand beyond the logical perimeter of their customary catchment area.  So Johns Hopkins Hospital is spending money to recruit patients to Baltimore from New York City - competing on New York Presbyterian Medical Center's turf.  It's said only one half of the dollars spent on advertising really works.  Since advertising is such a large part of the nation's health care budget, a great deal of money could be saved if we knew which half that is.


When entering the medical maze today, the odds of finding a solo medical practitioner or one in a small group are about the same as sighting a Packard on the interstate.

What We Know And Don't Know

A story that recently appeared on the front pages of many newspapers involves the increased risk of breast cancer in women exposed to diethylstilbestrol - DES  while in utero.  This drug was widely used to prevent miscarriage in women who experienced vaginal bleeding  in pregnancy.  In the 1970s, twenty years after the widespread adoption of DES for the management of threatened spontaneous abortion, an unusual form of vaginal cancer began to be found in girls and young women.  Although it took some time to uncover the cause and effect relationship, it was shown that if a woman took DES between the 5th and 18th weeks of pregnancy her female offspring were at significant risk of developing the cancer.  Years later it became clear that there were also effects in males exposed to DES in utero - such as diminished sperm counts that compromised reproductive function.  More recently it was found that children of those exposed to DES in utero - the grandchildren of women who were given the drug during pregnancy - have abnormalities of the reproductive tract possibly as result of that exposure.  This suggests a potential epigenetic effect; a heritable change in the way genes behave without changing the genetic DNA itself.   In fact, 10 years after the adverse effects of DES were identified and several studies confirmed it was ineffective in preventing miscarriage it was still being prescribed for that indication.         
 
This complicated story might be considered of historical interest only were it not for the fact that more than forty years after the significant risks of DES were identified, we still have not established an effective early warning system to minimize such untoward events.   Dr. Steven Nissan, a prestigious cardiologist at the Cleveland Clinic, recently complained about the inability of the Food and Drug Administration to fullfill its mandate to sound the alarm about drugs with significant adverse reactions.  He said  "the agency is extraordinarily slow to act on safety issues and has compromised patients."   http://newsatjama.jama.com

Most recently the drug pioglitazone, brand named Actos, used in the treatment of diabetes has been associated with an increased risk of bladder cancer.  The Food and Drug Administration has advised it should not be used in patients with a history of or active bladder cancer.  Furthermore, the advisory includes cautioning patients to report signs or symptoms of bladder cancer including blood in the urine, urinary urgency, pain on urination, back or abdominal pain.  All this is based on a 10 year study with an increased risk seen in patients with the longest exposure to the drug.  In France, similar findings were reported and sale of the drug was suspended.  In Germany, the official response was to advise that the drug be limited to patients currently using it.


There is no medicine that does not have adverse side effects, many are serious and some life threatening.  For example, as many as 1 million patients in the United States may be taking two medications each of which  taken alone have no effect on blood sugar but taken together can lead to increased blood glucose. This would present a major problem for anyone with diabetes.  This finding was uncovered by data mining the FDA's adverse reporting system, AERS http://www.fda.gov/Drugs/InformationOnDrugs/ucm135151.htm
Clearly, patients should explore this resource to learn what is known about their medications and the potential interactions among them. 

One widespread factor that may affect the safety of any medication is environmental exposure to chemicals that have the potential for interactions, including increasing or decreasing the potency of a given drug dose or changing the rate at which the drug is metabolized.   Bisphenol A - BPA - a compound used to make plastic hard and clear is found in many products from eyeglass frames to plastic bottles and jars and the lining of beverage cans.  It has been shown to interfere with the function of the endocrine glands of animals.  There are reasonable questions about it's biochemical activity in humans.  As of today the answer is we just don't know.


The history of medicine is crowded with flawed notions held long after clear evidence not only questioned their validity but proved they were erroneous.  One might think this would have resulted in physicians being less certain about their practices and more humble in the positions they promote with such authority.  A reduction in physician hubris could result in patients being less intimidated. Absent that fundamental change in  physician behavior, patients must be alert to the risks associated with actions based on conclusions that may have been arrived at as a result of incomplete or inaccurate information; and the failure on the part of physicians to admit what we know, what we're unsure of and what we really don't know.   

Health Care - Looking at Some Numbers

This year we will spend roughly $2.6 trillion on health care in the United States, $8,000 per capita, twice as much as any other country spends.  Because our health care system is inefficient, variable in quality, and disorganized, by many measures it produces what can only charitably be characterized as mediocre outcomes compared with many other countries that spend far less.


Five federal organizations largely oversee the health care system, each has its own budget and the discretion and power to affect how health care dollars are spent.  The National Institutes of Health is the research arm and acts as the conduit to put new findings into practice.  The Centers for Disease Control and Prevention deals with public health issues such as infectious diseases.  The Agency for Health Care and Quality and the Centers for Medicare and Medicaid Services focus on the organization, delivery and financing of the system.  The Food and Drug Administration has oversight of medical devices and drugs.  Each of these organizations is highly politicized and as a result subject to the lobbying efforts of a diverse set of constituencies on both sides of almost any relevant issue.    

An examination of how the $2.6 billion is allocated shows that approximately 20% is for physicians services, 30% goes to hospitals, 10% for medication, and 7% is spent on administrative expenses, with the remainder going to long term care, government health activities and other ancillary health care programs  http://www.kaiseredu.org/Topics/Costs-and-Spending.  So fifty percent of the health care costs are accounted for by physician and hospital charges.


In 1970, there were approximately 330,000 licensed physicians in the country, the population was 208 million and we spent about 7% of the GDP on health care. Thirty years later, by the year 2000 the population had increased to 282 million - an approximately 35% increase - there were 700,000 physicians - a 109% increase - and health care costs were 13% of GDP.  In the last ten years, the population has grown by 10% to 310 million, there are now almost 1 million physicians, a 42% increase, and we are spending 17% of the GDP on health care.    

These data are consistent with the claim that physicians in the United States are paid on average twice that in Western Europe and Japan. It turns out to be also is true for medical administrators.  This is in part due to the concentration of physicians in high tech specialties as contrasted with primary care doctors where the former report average incomes in several specialties of over $1 million/year  http://www.studentdoc.com/salaries.html.  The uneven distribution of physicians throughout the country, with wide variation in the ratio of physicians to population from state to state and between cities and rural areas, contributes to variability in medical costs.  One factor stands out in determining the location of medical practitioners; namely the ability to pay for medical care as evidenced by per-capita income of the people of the community.  Where a community is financially able to support physicians, medical practices are established. 


In order to rationalize our expenditures on medical care it is necessary to recognize that it is a unique commodity.  The consumer recognizes they don't have the capacity to critically judge the quality or value of care they receive, sometimes even after the fact.  Historically, physicians had complete control of the process; from judging a patient's need for service to the timing and conditions under which to provide it .  Now, in some cases these decisions are being shared with third party payers.


Since matters of life and death are involved, patients believe only one physician should be vested with the authority to provide care.  There is enormous resistance from patients to the idea of permitting any other agency to be injected into this process and they are often reluctant to consider a different provider which they would do if the forces of economic supply and demand were operating - as they do in almost every other business transaction.  The conditions surrounding the delivery of medical care are unlike those which characterize ordinary economic phenomena because the commodity itself is often priceless. The inherent inequality between the patient and the physician contaminates the entire transaction.  The notion of informed consent is at best only a shadow or outline of a patient's understanding of the essentials of the transaction.   Perhaps the most important change that would affect how we spend fifty percent of our health care budget is to correct this imbalance. 


  


   

From Overweight to Obese

Based on current trends, unless there are major changes in our eating habits and level of physical activities, half of the adults in the United States will be obese by the year 2030,  www.thelancet.com.  If you are currently overweight, the probability is extremely high that in time you will become obese - where overweight is defined as a body mass index, BMI, over 25 and obese as over 30   If a child is overweight, the probability that child will be obese as an adult is close to one hundred percent. 


The endless advertisements, television commercials and self-help diet books are evidence of the absence of an easy fix.  The problem is already contributing significantly to the increasing incidence and costs associated with diabetes, cardiovascular disease, stroke, and osteoarthritis.   

If anyone had a cure for this problem, the vast diet industry would go the way of buggy whip manufacturing.  It turns out the common weight-loss wisdom of reducing intake by about 500 calories a day will result in slow and steady weight loss of about a pound per week is flawed.   That rule doesn't take into account the way the body adapts to changes in diet.  As anyone who has lost weight will tell you, as their weight went down, if they wanted to maintain their reduced weight or lose more they had to consume still fewer calories.  If you are accustomed to taking in 2000 calories a day and after losing weight need only 1750 to maintain your lower weight, you will feel hungry; if you take in 2000, you won't feel hungry but you will re-accumulate the weight you worked so hard to lose.

Taking a realistic period of time for weight loss into account, it appears that for an average overweight adult a reduction in caloric intake of about 15 calories a day will lead to an eventual bodyweight change of about 2 pounds  - with half of the weight change being achieved in about 1 year, while 95% of the weight loss will take about 3 years.  Like so many fundamental characteristics of biological systems, genuine weight loss is a slow orderly process.   
   
Although we don't understand all the underlying mechanisms, most diets have reduced effects over time because the body adjusts to them.  This has been shown to be true for Slim Fast.com  http://www.slim-fast.com, Nutri Systems http://nutrisystems.com, Weight Watchers http://www.weightwatcher.com,  the Atkins diet http://www.atkins.com, the grapefruit diet http://www.grapefruit-diet.org, and even the water diet http://www.fitnessthroughfasting.com.   The exception to this rule seems to be a diet based on portion control.   Although there are no controlled trials of the strategy of limiting portion size, it appears that those who select this route for weight control decrease the size of their portions as they lose weight. 

The principles of weight loss seem to be deceptively simple.  If you take in more calories than you burn, you will inevitably gain weight - take in less and lose weight.  However there are some interesting nuances to this equation.  To burn some calories requires more energy output than others.   It turns out the number of calories burned given the same activity is also variable - not only from one person to another but even in the same person at different times.  If you have a very efficient metabolism, you will burn fewer calories for a given level of activity and the efficiency of metabolism varies within the same person.   To complicate matters further, it appears that metabolic efficiency increases with increasing age.  This helps explain why as we age we need fewer calories for weight maintenance.  If as you age you maintain a constant caloric intake, you will gain weight even if you maintain the same level of activity.   There are many other complex interactions that contribute to the increasing prevalence of obesity and its associated maladies. 


Although not based on a controlled trial, it seems the best investment for anyone trying to control their weight is a good scale.  It turns out those who simply weigh themselves every day when they get up in the morning, control their weight better than any other group.  Whether the object is weight maintenance or loss, this seems to reenforce their goal and results in their adjusting food intake and their level of physical activity.