January 3rd, 2014
2013: The Year of the Guideline
“I always pass on good advice. It is the only thing to do with it. It is never of any use to oneself.” — Oscar Wilde
This year culminated in an exciting flurry of academic activity. Long awaited guidelines for the treatment of cholesterol to reduce the risk of atherosclerotic cardiovascular disease and for the management of hypertension were finally released, both after agonizing delays.
While both guidelines have been mired in controversy, regrettably being undermined by some experts, they represent a sea-change for the field of preventive cardiology. Both place primary emphasis on evidence from randomized controlled clinical trials. This threshold means that the evidence base for clinical guidelines has never been stronger. The guideline writers should be commended for their efforts. Indeed, significant improvements in the health and well-being of our patients (and the population as a whole) are likely to result. For example, the use of evidence-based statin therapy should increase dramatically and reductions in atherosclerotic cardiovascular disease-related mortality are likely to ensue.
However, the guidelines have also inflicted significant collateral damage. The loss of LDL-Cholesterol targets and the increase of systolic blood pressure therapeutic thresholds (to 150mmHg for many patients) have shaken the very foundations on which many of us stand. One can only imagine what forefathers like Nikolaj N. Anitschkow would think of these new developments!
While full details of pros and cons of the new guidelines are outside the scope of this piece, it is disconcerting to realize that we appear, as a medical community, to have abandoned the idea of incorporating the full breadth of evidence-based medicine (including observation studies) into our decision-making armamentarium. When Francis Bacon first developed the scientific method, he proposed that causality can be approximated by interpreting the results of one’s observations. Thus, the very foundations of science were laid on the wide breadth of observation, not the narrow focus of randomization.
Admittedly, one must acknowledge that requiring randomized evidence as the basis for guidelines is the most robust strategy to deal with ever-present confounding and to ensure that recommendations are fully compatible with scientific truth. For example, no longer will physicians feel compelled to get patients to an arbitrary LDL-Cholesterol “target” with medicines that may have deleterious “off-target” effects.
However, multiple problems also arise with this thinking. For instance, at the most basic level, requiring results from randomized trials as the evidence base for guidelines is a problem when most clinical questions have no randomized evidence base in the first place. Thus, it appears that we will need many more randomized trials in the future. Indeed, the whole clinical research enterprise will need a major overhaul. Massively scalable mechanisms to conduct simple and varied randomized studies in “usual care” environments, as part of routine clinical workflow, are now urgently needed. This is the model of the learning health-care system.
For example, methods for embedding randomization within the clinical workflow of providers who use electronic health record systems are already being developed. However, besides cost, multiple hurdles obstruct progress in this field. These hurdles are significant and will require time and effort to overcome. Examples include difficulty acquiring streamlined consent given the current regulatory environment (which has not adapted to modern technology or comparative effectiveness research), poor physician motivation to sacrifice ever-precious time and effort to research as part of “usual care”, poor perception of research amongst patients, and a research hierarchy that does not engender inclusiveness (particularly with those non-academic providers who will be asked to contribute to this effort).
It is clear that new ideas and disruptive innovations will be necessary to make this learning health-care system a reality. However, once realized, it is possible that this reality could generate the volume of randomized evidence now necessary in the current era of cardiology guidelines. Of course, it would be folly to presume that we can perform randomized clinical trials for every single clinical scenario. No matter how much we think we can know, it is also unlikely we will ever have generate enough evidence such that there is no room left for different interpretations of this evidence. Disagreement will continue, indeed science depends on it. Such is the nature of inherently subjective human interpretations of data. Thus, randomization is not the panacea for our incomplete understanding of scientific truth, and we need to be careful not to become too inflexible to other (non-randomized) sources of data.
Personally, I think our current fixation on “hard facts” (evidence) from randomized clinical trials at times borders on utilitarian. I am reminded of Mr. Gradgrind, the headmaster from Charles Dickens’ Hard Times. In a famous passage, a visiting official asks Gradgrind’s students:
“Suppose you were going to carpet a room. Would you use a carpet having a representation of flowers upon it?”
The character Sissy Jupe replies, ingenuously, that she would because, “If you please, sir, I am very fond of flowers.”
“And is that why you would put tables and chairs upon them, and have people walking over them with heavy boots?” the official retorts.
“It wouldn’t hurt them, sir. They wouldn’t crush and wither, if you please, sir. They would be the pictures of what was very pretty and pleasant, and I would fancy -“
“Ay, ay, ay! But you mustn’t fancy,” cried the gentleman, quite elated by coming so happily to his point. “That’s it! You are never to fancy.”
“You are not, Cecilia Jupe,” Thomas Gradgrind solemnly repeated, “to do anything of that kind.”
“Fact, fact, fact!” said the gentleman. And “Fact, fact, fact!” repeated Thomas Gradgrind.
In conclusion, I hope that in 2014 we will not be consumed by the need for randomized “facts”, that the full breadth of evidence-based medicine will continue to be valued, and that guidelines can be seen as scientifically sound “advice.” And like all good advice, guidelines should be passed on and utilized wherever possible, as Mr. Wilde advises above. However, it is worth reminding ourselves that guidelines are not absolute rules. Thus, if the fully informed physician feels this “advice” does not apply to (or is of no use for) a specific patient, then they should continue to feel free to use clinical reasoning (inclusive of observational evidence, but with appropriate caution) to manage their patient.