Development of clinical practice guidelines ‘is a mess’

The world of clinical practice guidelines is a mess.

Regardless of what medical field you look at — oncology, cardiology, urology — looking at guidelines recommending treatment developed for different countries might give you vertigo, wondering which way is up.

Even something that should be as simple as recommendations for treating uncomplicated high blood pressure can differ greatly, depending on who funded the organization producing the guideline, whether the guideline makers used the best available evidence, and the involvement of financially conflicted authors.

To demonstrate our point, we will focus here on clinical practice guidelines for hypertension, the medical term for high blood pressure. Hypertension is a major contributor to cardiovascular disease globally, and lies at the epicenter of a huge number of diagnoses, medical activity, and drug treatment. Checking patients’ blood pressure and modifying it with drugs are a mainstay of primary care, and the management of hypertension is a vast global concern. Substantial evidence exists that the benefits of drug treatment outweigh the harms when the condition is appropriately managed.

Dozens of countries have created hypertension guidelines. Yet here’s the rub: Evidence-based guidelines vary from country to country and, at the moment, there is not a single definitive, non-conflicted, unbiased, hypertension guideline that lays out the optimal way to diagnose and treat hypertension. That’s hard to believe, but true.

Does a doctor start prescribing medicine to someone whose blood pressure is 130/80, 140/90, or 150/100? Does she initially prescribe one drug, or two? Is there a qualitative difference in which drug she tries first? Answers to these questions depend on which guideline she follows. And that’s a problem.

How a doctor treats high blood pressure shouldn’t matter whether the doctor and patient are living in Canada, Croatia, or Cambodia. It shouldn’t matter if the doctor seeks advice from the American College of Cardiology, the European Society of Hypertension, the World Health Organization, Hypertension Canada, or Malaysia Hypertension. But it does.

One recent study revealed a huge disagreement between recommendations in clinical practice guidelines produced by the American College of Cardiology and the American Heart Association, the European Society of Cardiology and the European Society of Hypertension, and the International Society of Hypertension. These three guidelines disagreed about a number of issues: cut-off blood pressure values for starting treatment; the best drug — or drugs — for starting therapy; the target for blood pressure with treatment; which cardiovascular risk estimation score to use to guide treatment; and more. Like we said, a mess. These differences confuse clinicians, hypertension experts, and the public worldwide.

As a narrower case study, we examined differences in two national hypertension guidelines, comparing Malaysian guidelines against the major one produced in Canada, where we live and work. There were notable differences, especially in the use of systematic reviews and the inclusion of authors with conflicts of interest in the guideline-making team. This resulted in different recommendations between the two.

Many clinicians accept that high quality, rigorous, systematic reviews should be the foundation of evidence-based health care decision-making. Such rigor is found in the thousands of reviews that make up the Cochrane Library, which owe their reliability to common and specific methodologies to limit bias and random error, as well as transparent reporting and editorial processes. (Disclosure: two of us, M.B.E. and J.M.W., are volunteer reviewers for the Cochrane Library.)

We were perplexed to see the Malaysian guideline citing many Cochrane reviews and incorporating that evidence into its recommendations while the Canadian guideline cited only a few. One possible explanation for this and other differences between the two sets of guidelines is the different levels of financial conflicts of interest among the respective guideline writers. Hypertension Canada is funded largely by several drug companies that make antihypertensive drugs, while the Malaysian group declared funding from one drug company and only allowed authors with no competing financial or professional interests to participate in developing its guidelines.

The Canadian group stated that the “development of the guidelines is fully independent and free from external influence,” yet its disclosures show that 33 out of 82 (40%) of the guideline authors have financial ties to drug manufacturers. Drug companies that “sponsor” guidelines do so out of their marketing budgets, so regardless of how public spirited they are, at the end of the day their involvement is shaped by sales and revenues.

This is also seen with other clinical practice guidelines, such as those recommending treatments for diabetes or cholesterol, where many authors involved in drafting guidelines declare numerous financial conflicts with pharmaceutical companies.

Financial conflicts of interest related to pharmaceutical companies have the potential to influence drug recommendations found in guidelines. This bias can often result in significant harm to patients. In the case of hypertension, this harm can be seen in unnecessary anxiety, falls and injury due to low blood pressure, excess spending, and so on.

The world needs a single independent hypertension guideline that would provide unbiased, evidence-based recommendations solely focused on what is best for people with high blood pressure.

When we published our findings, some guideline writers pushed back. They said it’s impossible to find experts without conflicts to work on guideline committees (though Malaysia demonstrates that isn’t true). They said it would be impossible to construct guidelines without the involvement of manufacturers (also not true). They argued that guidelines need to be locally produced and attentive to local conditions (while true to some extent, this obscures the fact that high blood pressure is high blood pressure regardless of race, color, creed, or nationality).

At the end of the day, the kind of treatment offered to people living with high blood pressure shouldn’t depend on what part of the world they happen to be living in.

It is entirely feasible to find independent and methodological and clinical experts and produce guidelines free from governmental or conflicted donor sources. It is past time for evidence experts from around the world to set up a process for producing a single, unbiased, International Hypertension Guideline that would follow strict evidence-based methodology and be updated regularly.

We believe that international cooperation on a variety of treatment guidelines — like those shaping recommendations in cardiology, diabetes, oncology, urology, and more — should also be able to create high quality, single sources of rigorous evidence-based treatment advice.

The current approach, as we’ve demonstrated with hypertension, shows how chaotic and counterproductive current standards for guideline creation are. The world’s people deserve better. We believe that once the world comes to realize how important this is, and how the current approach can be harmful, there will be no going back to the old fractured ways.

Alan Cassels is a pharmaceutical policy researcher at the University of British Columbia’s Therapeutics Initiative and its communications director. Mohamed Ben-Eltriki is a community pharmacist in Vancouver, Canada, and a postdoctoral researcher with the Cochrane Hypertension Review Group and the Therapeutics Initiative. James M. Wright is a clinical pharmacologist at Vancouver Coastal Health, an emeritus professor of anesthesiology, pharmacology, and therapeutics and of medicine at the University of British Columbia, a coordinating editor of the Cochrane Hypertension Review Group, and a member of the oversight committee for the Therapeutics Initiative.