Never did I read a document so impregnated with intelligence and tenderness directed to the medical profession!!! I can say that I am happy to have already talked with Professor Derek R Matthews from Oxford (UK).

1. editorial
Diabetes, Obesity and Metabolism 14 (Suppl. 1): 1–2, 2012.
© 2011 Blackwell Publishing Ltd
Wisdom-based and evidence-based medicine
Evidence seems to be what we need in medicine. Decades ago,
at the time of the Spanish Civil war and Second World War, Regulators
Archie Cochrane, a young physician in a prison camp, worried
that his advice to colleagues about treating tuberculosis might
not be appropriate and feared indeed that some procedures
and medications might be harmful: ‘I knew that there was “Experts” Research
Evidence
and
no real evidence that anything we had to offer had any effect Guidelines
Base
on tuberculosis, and I was afraid that I shortened the lives
of some of my friends by unnecessary intervention’ [1]. So
Decision
began the history of evidence-based medicine, and its laudable
enlargement and formalization—the Cochrane Reviews and
the Cochrane Collaboration—with their careful approach to
grades of evidence. Standing on this firm platform of evidential Physician Patient
practice we are sure in our prescribing, now, that tuberculosis
can, usually, be eliminated by triple therapy, that ACE inhibitors
lower blood pressure and can improve longevity, and that DRM 2011
peptic ulceration is often caused by Helicobacter pylori and
can be treated with a 1-week course of antibiotics. These are
Figure 1. Decision making is a four-sided process: no one domain has
triumphs of research and the accumulation of evidence. primacy. Regulators have effects on research generally, but influence and
However, with time the complexity of medicine increases. are influenced by evidence and by experts.
Faced with diabetes, what are we hoping to treat? If we are
simply trying to improve mortality does this not marginalize
the significance of reducing morbidity? Would our patients medicine which is to do the right thing for the right reason.
prefer to live longer but live with renal failure? Is the prevention No physician is needed when therapy can be read from an
of stroke less important than absolute longevity? At this point in algorithm.
our medical practice we arrive at a dilemma. We have evidence- In these proceedings, we have published articles by four
based medicine pointing in different directions depending on opinion leaders in the field. They address the issue of the role
our choice of what it is that we are trying to treat or prevent, of therapy in general and sulphonylureas in particular from
and so it emerges that clinical practice becomes knowledge- different standpoints and are a perfect illustration of the ways in
based rather than evidence-based. Knowledge is wider than which medical practice moves forward. We need insights into
evidence. Evidence implies that we are facing a situation where the molecular basis of sulphonylurea action [2], into clinical
a decision can be right or wrong. The word ‘evidence’ is most studies of sulphonylureas—and gliclazide in particular [3] and
commonly used in courts of law where a jury is assessing we need experience in synthesizing the totality of evidence
whether something is right or wrong. Is someone innocent [4, 5].
or guilty? Courts do not like the concept of someone being Intersecting with what we know and the trial evidence
are some other crucial considerations. We cannot prescribe
e d i tor i a l
partly guilty! But in medicine our knowledge tells us that agents
or procedures or policies or combinations of drugs work in regardless of cost in the current environment; we cannot ignore
general but not in everyone. The cry goes up that we need more regulators even when we think our opinion is better than theirs;
evidence. But if we were going to use randomized control trials we cannot ignore the pragmatic issues of availability and supply;
to look at permutations and combinations of five agents that finally we cannot ignore the role of the patients themselves in
we know would work to reduce glycaemia in type 2 diabetes, being part of the decision-making process. All the therapeutic
conclusions from randomized controlled trials are based on
then we would need a trial with 120 arms. This is never going
mean or median response—when faced with a single patient
to happen.
even our strongest evidence can fail us. Is this patient ‘typical’ or
So we decide, discuss and prescribe on the basis of our
was the trial of ‘typical patients’? So our guidelines are flawed,
knowledge base. Our deliberations may not be strictly evidence-
not in their generality but in their specificity. Explicit problems
based, but we would hope they might be rational. Figure 1
with guidelines include:
shows how the evidence base that we embrace is not necessarily
the leading influence on a therapeutic decision—indeed were • Guidelines cannot usually be strictly evidence-based,
it to be we would feel that much had been lost from the art of simply because the head-to-head trials of the wide

2. editorial DIABETES, OBESITY AND METABOLISM
range of agents have not been carried out, or drugs hypoglycaemia, social environment (e.g. living alone), age
used in previous trials are now no longer prescribed or or even life expectancy in some circumstances.
available or thought to be appropriate. In the Consensus
We have to begin an open dialogue about patient wishes,
statement Algorithm published in 2009 [5], for example,
fears, circumstances and resources. This is neither evidence-
after the use of metformin the only subset that was
based medicine nor solely knowledge-based medicine. It
labelled as having a ‘well-validated’ evidence base was
requires listening, thought, experience and wisdom. It is
for the use of sulphonylureas—based on the UKPDS.
rationally based medicine which in the best hands is
The guidelines explicitly suggested, however, that what
compassion-based medicine too.
should be used should be ‘sulfonylureas other than
glybenclamide (glyburide) or chlorpropamide’. However,
these agents were exactly the ones that were used in the D. R. Matthews
UKPDS. Professor of Diabetes Medicine, University of Oxford;
• The US and European regulators take a different view NIHR Senior Research Fellow;
about pharmaceutical agents, so there cannot be an agreed Oxford Centre for Diabetes, endocrinology and Metabolism
clinical view that has transatlantic credence, much less a
global one.
• ‘Expert’ committees may have their expertise limited References
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2 doi:10.1111/j.1463-1326.2011.01514.x Volume 14 No. (Suppl. 1) January 2012