by Milton Packer MD
October 17, 2018
During a recent conference, I listened to the speaker opine on a controversial topic. His talk started and ended with slides that copied the text of guidelines issued by several national organizations and societies. When the guideline slides appeared, he dutifully read out their recommendations with reverence.
When the conference ended, I asked the speaker why he had placed so much emphasis on the guidelines. (Below is a paraphrase of our discussion.)
Him: Well, they’re the guidelines! They represent the right and wrong way to do things.
Me: I know you must think so. You cited them verbatim, chapter and verse. You took what they said literally.
Him: Of course, I did. The guidelines are the authoritative word!
Me: Really? Do you know who wrote them? Do you remember what evidence they cited? Are you aware of the evidence that they ignored? Do you know who reviewed the document? Do you have any idea whether the reviewers’ opinions were taken seriously?
The speaker understood my points, but he was not going to concede easily. So he went with his best counter: What else is there?
My response: Well, you could examine the literature yourself, analyze the relevant studies in detail, and formulate your own opinion.
His final reply: I can’t do that. I do not know how to do that. And even if I knew how, I do not have the time to do it. I need to rely on the guidelines. It is all that I have.
Yes, he was right. It was all that he had. He revered the guidelines as some revere biblical scripture. The guidelines represented his only path to the truth.
But guideline documents do not deserve to be worshipped.
I have been a member of many guidelines committees. And I can confidently say that it is a messy process. With due homage to John Godfrey Saxe, sausage-making looks pristine by comparison.
Typically, each committee member is asked to write one section of the document. And at the end, the entire committee is supposed to critically review everyone else’s work. But sometimes it doesn’t work that way.
Few have the time to examine the entire document carefully; most are happy to believe that their colleagues have carried out their tasks satisfactorily. When the committee meets face-to-face, the primary goal is to move the document to the finish line. Given the time pressures, it is often easier to accept the approach of a fellow committee member than to challenge it. One or two determined members can have an outsized influence on the committee’s deliberations.
When the committee has exhausted its efforts, the sponsoring organization can hope that misstatements might be captured and corrected when (or if) the documents are sent out for review. But the authoring committee is not obliged to accept any of the recommendations or criticisms of the reviewers.
National organizations try to minimize conflicts of interest when choosing the members of guidelines committees. But they screen for financial conflicts, not intellectual ones. Without doubt, prior personal involvements can be influential.
Take, for example, the 2017 hypertension guidelines from the American Heart Association and the American College of Cardiology (AHA/ACC). That document changed the criteria for the diagnosis of high blood pressure, thereby (as many have noted) placing an enormous burden on the U.S. population and primary care physicians. The recommendations of the document were heavily influenced by the results of one highly controversial trial, the SPRINT study. Interestingly, several key members of the hypertension guidelines committee had played an important role in that trial.
If the SPRINT trial had been sponsored by a pharmaceutical company, would the participation of SPRINT trialists as primary authors on the guideline committee have been allowed?
The hypertension guidelines subsequently issued by primary care organizations and cardiology organizations in Europe did not endorse the principal recommendations of the ACC/AHA document. From my own perspective, the guidance provided by the ACC/AHA with respect to the management of blood pressure in patients with heart failure made no sense and were not evidence-based. Yet, they still stand to this day.
It gets worse. Last year, the AHA and the American Stroke Association jointly issued a guideline regarding the treatment of stroke. Shortly after its issuance, large sections of the document were retracted. Amazingly, this action was taken against the express wishes of the guidelines committee. In 2014, an ACC/AHA guideline on valvular regurgitation adopted an ill-advised classification system, and then, reversed course 3 years later.
Most guidelines committees use a system that ranks evidence in a nonsensical manner. According to the current approach, a meta-analysis of two small poorly done trials is deemed to provide a higher level of evidence than a single large-scale definitive trial. And a single large-scale definitive trial is assigned the same rank as nonrandomized observational studies. It is a silly approach to the ranking of evidence. Better approaches exist, but they are used by very few.
Many aspects of the guidelines simply reflect the fashion of the times. As I have previously noted, over a period of 10 years, the use of digoxin in heart failure was downgraded twice — without any new data from randomized trials to justify the change in recommendation.
Last week, John Ioannidis (Stanford University) took the discussion about guidelines to an extreme.
In his mistaken belief that guidelines were somehow sacred, he suggested that they best be developed by expert methodologists who have no knowledge about the clinical issues involved.
Oh please! I consider myself to be a meticulous methodologist, but do not ask me to develop guidelines for the treatment of gout or prostate cancer. First and foremost, guidelines are clinical documents. Methodologists who forget that suffer from incurable hubris.
Here is my solution to our current quagmire. We need to understand what the guidelines really are. Guidelines represent the opinions of its authors. Nothing more and nothing less. Their text is worth reading, but the document should not be the focus of worship. Guidelines are not biblical scripture.
But then again, biblical scripture has its own history of flexibility.
Unbeknownst to many, the messages delivered in the Bible have changed considerably over the years. The early Christians made choices as to what “books” would be included or left out of the New Testament. Early translations of the Bible into English emerged as part of the Reformation, but King James I did not like them, so he commissioned an entirely new translation, which adhered to his political imperatives. The Puritans were horrified, and they took their own (earlier) version of the Bible to the American colonies.
You do not need the help of a formal organization to achieve spiritual fulfillment or intellectual enlightenment. And you do not need “official” guidelines to tell you how to analyze scientific evidence or practice medicine. If you choose to follow someone else’s opinion, you may get what you pay for.
Packer recently consulted for Actavis, Akcea, Amgen, AstraZeneca, Boehringer Ingelheim, Cardiorentis, Daiichi Sankyo, Gilead, Novo Nordisk, Pfizer, Sanofi, Synthetic Biologics, and Takeda. He chairs the EMPEROR Executive Committee for trials of empagliflozin for the treatment of heart failure. He was previously the co-PI of the PARADIGM-HF trial and serves on the Steering Committee of the PARAGON-HF trial, but has no financial relationship with Novartis.