Friday, June 1, 2007

On evidence based medicine and the art of healing

As a clinician, I am often faced with the reality of having to balance the art and science of medical practice.This concept- so basic- yet so important to the medical profession echos the noble call of the Hippocratic Oath. James Herriot refers to this fusion of the heart and mind eloquently by describing the sublime and humble satisfaction one feels upon a job well done.

This uniquely human fusion is in large part a learned skill attained through the hard and arduous process of real life experience. As emotionally satisfying as it can often be, this special quality of clinical practice is a realm fraught with dangers and potential pitfalls. The repercussions of ignoring the art for the science, or vice a versa can lead a professional on tangents that are not conducive to practicing solid medicine.


Among these, is the danger of succumbing to the seductive song of the placebo effect with its many manifestations. Unfortunately, many complementary and alternative modalities rely on methodologies that rely heavily on nebulous, difficult to define powers, fields, and "Elam Vitals" of varying types and origins. These ideas are based on foundations laced together more with faith and belief than with demonstrable, repeatable observations. Here one can begin to discern the elusive placebo at work.


Though, there is nothing in general fundamentally abhorrent about the concept of the placebo, doctors of medicine need to tread with great care when encountering it. Offering emotional satisfaction to a patient is very important, but it needs to be done while utilizing effective, plausible, and when possible, established evidence based methods.


At the risk of repeating a familiar theme in this blog, the inexorable, sometimes plodding- yet flexible and malleable- nature of the scientific method provides a coherent method enabling truth. It is fundamentally critical for practitioners to inherently understand the role of science in medicine and how it works in the discovery process of disease.


That said, science is indeed a human endeavor fraught with instances of egotism and bias. Even so, it has proven to be the best self correcting, objective system designed up to this point. By striving to methodologically understand the natural processes of health and disease, our own ego and assumptions can be held to the fire, and we can, as doctors, take our place within the honorable task of effectively helping others.


Important among these processes is the role that the natural history of disease plays in our understanding of how any therapeutic modality works.We should be shrewdly skeptical of “wondrous” cures attributed to our skill and maintain a healthy dose of humility of who we really are. In this context, the placebo effect becomes a comprehensible phenomenon. The elusive and mystical qualities of its action disappear and its boundaries become better defined. The dilemma of ethical doctor/client relationships is less of an issue if clinicians can avoid creating false hope.


Indeed, the ethical consideration of utilizing the placebo as any part of a therapeutic process has garnered significant discussion among the medical community. In the world of veterinary medicine, this problem seems more acute due to the fact our patients are not the decision makers for a given treatment and it is more critical for the veterinarian and client to offer appropriate care.


A retired clinician, in an editorial I read, offered an interesting twist to this ethical dilemma. Given the hypothesis that some placebo effect occurs in any doctor/patient relationship (or in other words, that the outcome experienced by a patient equals evidence based therapy plus the placebo effect) he noted; “What are we to do when a situation arises that seems to call for the use of the placebo effect? …I suggest that it is acceptable to use the placebo effect provided there is no more than a negligible risk of harm and the cost of the “therapy” is insignificant...we should not abdicate to others the utilization of the placebo effect where warranted. By virtue of our university medical education and post-graduate training, we are best positioned to understand the dynamics of illness and select optimum treatment- including the placebo effect- with the least chance of error or harm.”


He assumed a placebo effect by the very existence of the client experience and he may very well be right. I think he confuses a whole set of qualities with the placebo. These are, in large part, those human communicative skills that a clinician needs to master to "connect" with the patient or care giver- no magic placebo needed. It is important to underscore here that the placebo in and of itself is not a treatment option in the realm of modern medicine. However, we need to understand the importance and potential influence of human bonding within the context of the client/doctor/therapy interaction.


It is therefore incumbent on the guardians and care givers, especially of children, the impaired, and animals to provide evidence based methods of treatment when ever possible. This is challenging with today's misrepresentations of which standards of care are effective and which are not. The lack of solid scientific education among the general population (at least in the US) exacerbates the problem. The standard perception of the “right to choose promulgated by many alternative medical and non-medical authorities in the human and animal fields creates a situation where the basic foundations of medical practice become fuzzy and indistinct to many. Disconcertingly, these professionals do not question the ethics of providing unproven medical therapies without caveats, representing some alternative modalities as "another" effective therapy.


The placebo effect, from this point of view, can be easily abused. It is therefore important to approach medicine using the evidence based process, under regulation, licensure, and standards. Within this framework the “right to choose” becomes a safer action and the placebo put in proper context.


The placebo effect has a variety of human to human triggers. It can originate from a touch, belief, or object. It seems to come in many forms and strengths. Ultimately, the placebo falls into the domain of the brain. When other qualities such as regression to the mean or conditioning are teased from this phenomenon it may be a uniquely human characteristic involving empathy.


The degree of empathy expressed by the medical professional increases the compliance of the patient in very direct ways. By spending a small amount of time understanding these interesting effects, the health provider can maximize the positive aspects within the art of medicine. The placing on of the hands, involving the patient in a conversation and asking questions within the context of the examination has tangible beneficial effects.These are qualities that alternative practitioners rely on, but it is not exclusively their domain. These actions are an intimate part of any doctor/patient relationship.


The evidence based approach provides a consistent formula whereby several spheres of influence can jointly impact a clinical outcome. This method takes into account many of the perceived placebo effects while focusing on science based medicine. This form of practice continues to gain popularity in the veterinary world and has made solid inroads in human medicine. As described by many human and some veterinary studies, there are three general areas in the doctor/patient relationship that work together; the clinicians experience, the clients’ perceptions, and the body of evidence based knowledge with respect to the presiding malady.


The goal of this approach is to maximize effective therapies while taking into consideration other factors that may affect the therapeutic outcome. By taking into account particularities of the clinician and client, it is possible to customize treatments to a degree. This may allow the flexibility needed to maximize compliance and allow for the best outcome for that particular case. It is not a "follow the recipe" modality as many suggest.


In essence, the evidence based approach allows room for such effects as socio cultural influences and clinician experience and reduces any dependance on hard to define entities such as the placebo effect.It takes into account many of the variables that can affect outcomes of therapy and keeps them within the bounds of solid medicine.


Evidence based medicine provides an encouraging approach to medicine that gives life and vigor to clinical practice while providing effective therapies in a flexible way. The humanity of medicine is preserved and the best medicine is offered.

5 comments:

Gregory D. Pawelski said...

Strong Evidence From Clinical Trials?

In life or death situations, one must make judgements based upon preponderance of available evidence as opposed to proof beyond reasonable doubt. It seems obvious that "evidence-based medicine" proponents may fail to apply this common sense standard on a consistent basis.

To cite an example in cancer medicine, a fraternal medical society establishes a policy recommending against the use of a diagnostic test as an aid to drug selection in cancer chemotherapy, based on reviews which specifically excluded from consideration studies reporting the predictive accuracy of the test, and including only studies relating to the efficacy of the test in improving treatment outcomes.

This is especially curious, as predictive accuracy is the chief criterion traditionally used to validate all diagnostic laboratory tests currently in use in cancer medicine. Were proof of efficacy (particularly in prospective, randomized trials) to be the standard for evaluating laboratory tests, then clinical oncologists would have to abandon all the laboratory tests currently used in the management of cancer patients, as no tests would pass this standard.

Clinical investigators have too often descended into an exhaustive study of hypotheses which are ultimately of limited importance. Many treatments are of such limited effectiveness that they do not deserve to be protected from the competition of other approaches which are well grounded in peer review science, but which have not yet met the most demanding standards of "evidence based medicine."

Evidence-based medicine is a trial-and-error process of a clinical trials to see what might "appear" to be improving survival. It is the mindset of rewarding academic achievement and publication over all else. There is this aurora that organizations, government agencies, scientists, researcher and even practitioners work together, sharing information for the benefit of patients.

Each group has its own priorities and its own agenda. Moreover, the image of cooperation between these different groups only gives the illusion that reform isn't needed. The present system exists to serve academic achievement and publication, but not to serve the best interests of people.

Also, whatever clinical response that has resulted to the average number of patients in a randomized trial, is no indication of what will happen to an individual at any particular time. They are trying to identify the "best guess" treatment for the average patient. You cannot mate notoriously heterogeneous diseases into "one-size-fits-all" treatments.

wandering primate said...

"In life or death situations, one must make judgements based upon preponderance of available evidence as opposed to proof beyond reasonable doubt"

But this is taken into account when considering the spheres of influence in EBM-the clinicians experience, the patients perception, and avialable knowledge- proof beyond a reasonable is not what is ultimately sought- a framework for working within reason is.

"a fraternal medical society establishes a policy..."

Bias and "established" authority problems are common every where in human endeavor. A system that can change, correct, and bend as new information comes, as in EBM, is more in the interests of patients- what other system would you suggest?

"as predictive accuracy is the chief criterion traditionally used to validate all diagnostic laboratory tests currently in use in cancer medicine"

I don't follow here. There are many times the use of statistical analysis is the only way to get a clearer feel for the results of one treatment or another...this is a valid and accepted way of garnering a body of evidence- you don't always need "proof of efficacy" in a black/white manner you seem to allude to. A large part of medicine involves dealing in shades of grey- we need to wade through these shades effectively.
Laboratory tests fall into the the area of providing varying degrees of information- sometimes helpful, sometimes not.i.e., Electrolyte anomallies might direct one towards correcting secondary issues, or vary a chemo protocol. An exploratory biopsy might ID, to a high degree, what chemo to use.

"Many treatments are of such limited effectiveness that they do not deserve to be protected from the competition of other approaches which are well grounded in peer review science, but which have not yet met the most demanding standards of "evidence based"

I'm not sure, but this seems to be a call against the "establishment" and science based reductionalism. I'm no fan of inflexible "institutional" heirarchies and have big issues with many policies in our present medical system, but the basic science base is sound. However,I agree that continually researching treatments that persistently show questionable efficacy call into question plausibilty (take acupuncture or homeopathy for instance). Many treatments with little RCT info are often used based on plausibilty, efficacy in similar biological systems... especially in veterinary medicine.

"the image of cooperation between these different groups only gives the illusion that reform isn't needed"

Who said reform isn't needed? Still, the overall effect all these groups have is far superior than some type of anarchy were whatever suits ones fancy goes...

"The present system exists to serve academic achievement and publication, but not to serve the best interests of people."

Like I said, there are problems, but I disagree with this blanket assessment- A small example would be the generally increased life span in many domestic animals as well increased capacity to diagnose and correct many pathologies in them just in the last 20 years in vet med.

"They are trying to identify the "best guess" treatment for the average patient. You cannot mate notoriously heterogeneous diseases into "one-size-fits-all" treatments."

This is patently untrue and a strawman version of EBM. If you look into the detail and meaning of this approach, it is ultimately
a search for what really works-it takes into account varaibles including the clinician as well as the patient-the fact that it is a human influenced scientific approach will probably garauntee imperfection and drama-but it is a self-critical evaluation that can self-correct, unlike many "other ways of knowing" modalities.

Greg Pawelski said...

Evidence-based medicine doesn't rely on clinical insight, medical training or personal experience. It is based on data from medical journal articles, epidemiology and economics, which relies on randomized clinical trials, which doesn't even require a medical education. Nonphysicians trained in social science, science or even public policy analysis, have judgement over medicine. Where doctors defined the "standard of care," now payers and purchasers of medical services redefine the standards for appropriate medical care, encouraging doctors to act in ways to promote their financial interest when they make medical decisions.

When evidence from a clinical trial suggests that one therapy is superior to another, it can be used to change prevailing medical practice. The effects of this information requires that some medical specialties and medical suppliers lose income while others gain income. And sometimes evidence may be preliminary rather than well established so that their long-term effects are not known.

I agree, you don't always need "proof of efficacy" in a black/white manner (as you call it). A large part of medicine involves dealing in shades of grey. However, laboratory and radiographic tests can help evaulate the "efficacy" of therapy. Laboratory tests can provide varying degrees of information. Like bacterial culture and sensitivity testing can steer the most beneficial anti-biotics against infections, cell culture assays can identify those who may respond to adjuvant therapy. It is highly desirable to know what drugs are effective against particular cancer cells before these toxic agents are systemically administered. Predictive "accuracy" is the chief criterion traditionally used to validate all diagnostic laboratory tests currently in use in cancer medicine.

The "establishment" itself (NCI) has stated on its official cancer information website on "state of the art" chemotherapy, it is unclear whether single-agent or combinations of drugs is preferable for first-line treatment. No data support the superiority of any particular regimen. So it would appear that published reports of clinical trials provide provide precious little in the way of guidance.

The use of clinical trials to establish prescribing guidelines for evidence-based medicine is highly criticized because such trials have little relevance for the individual patient in the real world, the individuality and uniqueness of each patient. The sample of participants in a randomized controlled trial is typically drawn from those deemed most likely to benefit from the protocol. It usually excludes the very young or old, the non-compliant, and those with co-existing illness. In clinical trials, many patients are excluded because they could not complete the rather arduous treatment. So randomized comparisons are of healthier treated patients against all the controls, rendering a lot of trials invalid. While the evidence obtained from the clinical trial may apply to the sample of trial participants, it may have little relevance for the individual patient in the real world.

The is no proof beyond reasonable doubt for any approach to treating advanced cancer today. There is only the bias of clinical investigators as a group and as individuals.

wandering primate said...

--Evidence-based medicine doesn't
rely on clinical insight, medical training or personal experience.--

On the contrary, EBM relies intimately on them. EBM is "the conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient. It means integrating individual clinical expertise with the best available external clinical evidence from systematic research." (Sackett D, 1996)

The evidence, by itself, does not make a decision for you, but it can help support the patient care process. The full integration of these three components into clinical decisions enhances the opportunity for optimal clinical outcomes and quality of life.

--It is based on data from medical journal articles, epidemiology and economics, which relies on randomized clinical trials, which doesn't even require a medical education.--

Evidence-based medicine "converts the abstract exercise of reading and appraising the literature into the pragmatic process of using the literature to benefit individual patients while simultaneously expanding the clinician's knowledge base." (Bordley DR, 1997)

You need that DVM or MD title to put it all together for your patient.

--Nonphysicians trained in social science, science or even public policy analysis, have judgement over medicine. Where doctors defined the "standard of care," now payers and purchasers of medical services redefine the standards for appropriate medical care, encouraging doctors to act in ways to promote their financial interest when they make medical decisions.--

Here you are comparing apples to oranges. First, the general body of science based information is gathered by a broad representation of professionals from the basic sciences (chemistry, biology, biochemistry, physiology…), research physicians, tenured faculty, practicing doctors to name some. It is from this body of evidence and understanding that medicine needs to rely.

On the other hand, I agree that there are big problems with third party intrusions, socio-political interests, big corporate lobbying pressures…that inhibit the medical profession- but this is not EBM. That these special interests twist and deform whatever they touch does not change the essence of EBM, science, and an honest and open pursuit of knowledge. Here I think we might agree on many points.

--When evidence from a clinical trial suggests that one therapy is superior to another, it can be used to change prevailing medical practice. The effects of this information requires that some medical specialties and medical suppliers lose income while others gain income. And sometimes evidence may be preliminary rather than well established so that their long-term effects are not known.--

This is part of the human condition and the knowledge gaining process- a science based perspective at least provides a self critical, self correcting mechanism to seek the best balance through time.

--Predictive "accuracy" is the chief criterion traditionally used to validate all diagnostic laboratory tests currently in use in cancer medicine.--

Not sure what you mean here. The specificity and sensitivity of diagnostic, prognostic, and therapeutic analysis will vary depending on what you are evaluating- this includes the history and discussion with the patient, examination, and so on- the whole picture helps dictate the interpretation and validity of whatever the modality in question is.

--The "establishment" itself (NCI) has stated on its official cancer information website on "state of the art" chemotherapy, it is unclear whether single-agent or combinations of drugs is preferable for first-line treatment. No data support the superiority of any particular regimen.--

You need to look at what type of neoplastic process you are dealing with before you can state anything about treatment approaches such as chemotherapy. A plethora of information is available to assist in validating what therapies to use.

What the NCI says:
“When doctors discuss a person’s prognosis, they carefully consider all factors that could affect that person’s disease and treatment, and then try to predict what might happen. The doctor bases the prognosis on information researchers have collected over many years about hundreds or even thousands of people with cancer. When possible, the doctor uses statistics based on groups of people whose situations are most similar to that of an individual patient.”

--So it would appear that published reports of clinical trials provide provide precious little in the way of guidance.--

What the NCI says:
“A clinical trial is one of the final stages of a long and careful cancer research process. Studies are done with cancer patients to find out whether promising approaches to cancer prevention, diagnosis, and treatment are safe and effective.”

--The use of clinical trials to establish prescribing guidelines for evidence-based medicine is highly criticized because such trials have little relevance for the individual patient in the real world, the individuality and uniqueness of each patient. The sample of participants in a randomized controlled trial is typically drawn from those deemed most likely to benefit from the protocol. It usually excludes the very young or old, the non-compliant, and those with co-existing illness. In clinical trials, many patients are excluded because they could not complete the rather arduous treatment. So randomized comparisons are of healthier treated patients against all the controls, rendering a lot of trials invalid. While the evidence obtained from the clinical trial may apply to the sample of trial participants, it may have little relevance for the individual patient in the real world.--

“The evidence that supports the validity or truthfulness of the information is found primarily in the study methodology. Here is where the investigators address the issue of bias, both conscious and unconscious. Study methodologies such as randomization, blinding and accounting for all patients help insure that the study results are not overly influenced by the investigators or the patients.

Once you have determined that the study methodology is valid, you must examine the results and their applicability to the patient.

Clinicians may have additional concerns such as whether the study represented patients similar to his/her patients, whether the study covered the aspect of the problem that is most important to the patient, or whether the study suggested a clear and useful plan of action.

Anything that happens after randomization can affect the chances that a patient in a study has an event. Patients who forget or refuse their treatment should not be eliminated from the study analysis. Excluding noncompliant patients leaves behind those that may be more likely to have a positive outcome, thus compromising the unbiased comparison that we got from the process of randomization. Therefore patients should be analyzed within their assigned groups. This is called "intention to treat" analysis.

Blinding means that the people involved in the study do not know which treatments are given to which patients. This eliminates bias and any preconceived notions as to how the treatments should be working. When it is difficult or unethical to blind patients to a treatment, such as a surgical treatment, then a "blinded" researcher is needed to interpret the results.

Decision making involves choosing an action after weighing the risks and benefits of the alternatives. While all clinical decisions are made under conditions of uncertainty, the degree of uncertainty decreases when the medical literature includes directly relevant, valid evidence. When the published evidence is scant, or less valid, uncertainty increases.

Decision analysis is the application of explicit, quantitative methods to analyzing decisions under conditions of uncertainty. Decision analysis allows clinicians to compare the expected consequences of pursuing different strategies.”

--There is no proof beyond reasonable doubt for any approach to treating advanced cancer today. There is only the bias of clinical investigators as a group and as individuals.--

There is no proof beyond a reasonable doubt that gravity exists or that the sun will rise tomorrow, so?

Some thoughts:

“The medical literature is immense, but only a small portion of it is immediately useful in answering clinical questions. The literature reports the whole spectrum of the scientific research process -- the long journey from in-vitro studies to double-blind randomized controlled trials. This has been called the "wedge of evidence" or the "pyramid of evidence."

“An understanding of how various levels of evidence are reported and how this literature is organized will help the searcher retrieve the highest levels of evidence for a particular clinical question. High levels of evidence may not exist for all clinical questions because of the nature of medical problems and research and ethical limitations.”

Greg Pawelski said...

It is impossible to design a single chemotherapy protocol that is effective against all types of cancer. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability. It would be highly desirable to know what drugs are effective against your particular cancer cells before these toxic agents are systemically administered into your body. Having a good tumor-drug match not only would improve survival rates, it would be cost-effective and reinforce the necessity of choosing the right therapy the first time around.

Cancer chemotherapy could save more lives if pre-testing were incorporated into clinical medicine. The respected cancer journals are publishing articles that identify safer and more effective treatment regimens, yet few oncologists are incorporating these synergistic methods into their clinical practice. Cancer patients often suffer through chemotherapy sessions that do not integrate all possibilities. The objective of pre-testing is to provide the patient with more options to discuss with their oncologist and to bring about multimodality approaches to improve the probability of a successful outcome.

Pre-testing patient tumors can provide predictive information to help physicians choose between chemotherapy drugs, eliminate potentially ineffective drugs from treatment regimens and assist in the formulation of an optimal therapy choice for each patient. This can spare the patient from unnecessary toxicity associated with ineffective treatment and offers a better chance of tumor response resulting in progression-free survival.

Identifying patients with resistant neoplasms may not only spare them toxicity but may prolong their lives, by sparing them from the life shortening effects of ineffective chemotherapy. Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival above that achieved with empiric chemotherapy.