Monday, May 27, 2013

Treating the Patient vs Following the Book

There is an interesting article in JAMA comparing Evidenced (Guideline) Based Medicine versus Personalized Medicine. This is critical since the ACA fosters on physicians the EBM approach and may ultimately penalize them for deviating therefrom. After all it is the Government.

For EBM the authors clearly state:

Evidence-based guidelines are generated based on the body of clinical data available for a particular question. The highest level of evidence assigned in a guideline is based on multiple randomized controlled clinical trials. In general, randomized clinical trials have specific inclusion and exclusion criteria designed to represent a population broad enough and sufficiently enriched to attain a requisite number of end points and demonstrate a statistically and clinically significant difference in outcome. Subgroup analyses (both those that are prespecified and other post hoc analyses) are often performed to identify characteristics within the study population that are associated with greater benefit from the intervention, with no benefit, or even with harm. Yet these analyses are accompanied by warnings that findings should be cautiously interpreted.

 The classic example is the prostate cancer tests and the breast cancer monitoring. The problem is always the issue of the subgroups and the users understanding of these limitations. The authors specifically state:

Indeed, there is well-deserved skepticism regarding the utility and accuracy of subgroup analysis from clinical trials, and these analyses are therefore generally not used in the formulation of guidelines. Patients (including those enrolled in trials) have multiple characteristics, each of which may influence the behavior and significance of other characteristics. Analysis of a subgroup showing that a single characteristic influences outcome is of limited clinical significance unless multiple variables that may modify the importance of the single variable are considered. However, if well-conducted analyses from multiple sources demonstrate concordant findings, perhaps these subgroup analyses should be considered when guidelines are constructed and revised, given the impracticality of performing randomized clinical trials to answer the question of appropriateness for every possible subgroup.

 For example it is well known that prostate cancer is not the same in all men. Most is indolent and some highly aggressive.  But how does one tell the difference. The "Guidelines" fail in all manners of reasonableness in addressing this. 

Now the authors characterize Personalize Medicine as follows:

The President's Council of Advisors on Science and Technology noted that personalized medicine “refers to the tailoring of medical treatment to the individual characteristics of each patient. It does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not.

 Let us avoid any insight from the current president and his minions, for personalized medicine does really mean tailoring treatment down to the therapeutic level. For example, if we have a metastatic melanoma, then by understanding the receptor, ligand, pathway, and other elements broken in the mets we can develop not only a patient specific but CELL specific therapeutic. That is the future, and it is a future than can be achieved with what we have at hand today.

The authors conclude:

The conflict between guideline-based medicine and personalized medicine predominantly occurs when considering withholding a therapy that is recommended or supported by the guidelines but that may not be beneficial for an individual patient. 

If a subpopulation may not benefit from the therapy, it is important to identify the subpopulation and verify this finding in an appropriate clinical trial. This presents a genuine opportunity to deliver better health care at lower costs by withholding the intervention. Cultivating a health care culture poised to explore these opportunities is critical. 

This will entail more active participation from a range of stakeholders, including physicians who will need to embrace equipoise when the data support this position; insurers (including the Centers for Medicare & Medicaid Services) who have traditionally not been involved in the design, funding, and conduct of clinical trials; regulators who will need to develop policies to enable and support this type of patient-centered research; and health care organizations and quality-measurement groups who will need to develop more nuanced approaches to assessing quality of care and processes that monitor guideline implementation.

The key observation here is that as most physicians know all patients are different. Some benefit some do not. The reasons why are still often clouded in our ignorance. Will we allow our ignorance to dominate our treatments? Perhaps under ACA we not only will but must. Reimbursement may be the least of the problems. Failure to follow Guidelines, the "Rules", may very well place the physician at jeopardy. If the IRS has its say then perhaps failure to follow any Guideline may result in criminal charges, audits, and the like. This may be making physicians rule followers rather than diseases solvers.