The road to health care.

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The road to health care
Balancing benefits and harms of interventions is essential
“There are some patients that we cannot help; there are
none whom we cannot harm.”
Attributed to Arthur L Bloomfield
B
about 3400 a year.1Elsewhere in the world the rates are
up to six times higher.2Now compare that with the
extrapolated figure for the United Kingdom of more
than twice that number of deaths each year from
adverse drug reactions, estimated from the results of a
prospective study published in this theme issue of the
BMJ.3Now try to estimate the benefit to harm balance
of a road trip and the benefit to harm balance of a drug
that you have recently used.
But drugs are far from being the only inter-
ventions we use in health care; even when drugs are
prescribed they are often only part of an overall plan
of care. Other interventions include lifestyle changes,
surgery, physiotherapy, radiotherapy, rest, and a
panoply of other interventions that may be recom-
mended by medical and paramedical staff, relatives
and friends,practitioners of complementary and alter-
native medicine, and the latest issue of Cosmopolitan
magazine.
Even with drug treatments we often lack the neces-
sary information to estimate the balance between ben-
efits and harms. Randomised trials are primarily
concerned with addressing uncertainties about poten-
tial benefits and seldom focus on safety issues. More-
over, even when information about safety is collected,
the data may be sparse, may not be collected systemati-
cally, and may not be comparable from study to study.
This makes the benefit to harm balance difficult to
assess.
Consider how much more challenging it is to assess
the benefit to harm balance for non-drug interven-
tions. Often such interventions are implemented with-
out reliable evidence of their beneficial effects,let alone
their harmful ones. For example, most evaluations of
different prostheses in total hip replacement are
uncontrolled, and a systematic review found that the
primary evidence was too weak to draw valid
conclusions.4Cryotherapy is widely used to treat warts,
but evidence of its efficacy and safety rests on a hand-
ful of randomised controlled trials and is reportedly
both limited and contradictory.5Wax softeners are
used by the gallon, but we don’t know about their rela-
tive effectiveness, let alone their safety.6Children with
efore you next get into your car or walk out into
the street, reflect that the number of deaths
from road crashes in the United Kingdom is
bronchiolitis are segregated in many hospitals to
reduce the risk of nosocomial infection, but we do not
know if this is effective.7And we are still unable to
answer with certainty the age old question of which
position women should adopt when delivering their
babies.8
In some cases not only is there no evidence of ben-
efit, but we may remain oblivious to the possibility of
harm. How many times have you heard someone say
that even if an untested treatment is not going to do
any good it is unlikely to be harmful? But there are sev-
eral examples of interventions that were confidently
expected to be both beneficial and completely safe,
expectations that were not fulfilled. For example, high
concentrations of oxygen for premature babies, which
caused retrolental fibroplasia9; bed rest for low back
pain,which candelay
resuscitating critically ill patients with hypovolaemia,
burns, or hypoalbuminaemia, which probably worsens
outcomes11; and class I antiarrhythmic drugs, which
unexpectedly increased mortality after myocardial
infarction.12We banned relatives from accompanying
women during delivery in many hospitals,only to learn
decades later that this is far from ideal in most cases,13
and we have implemented some guidelines on how to
approach deliberate self harm without realising that
they were often wasteful of resources if not actually
harmful.14
In all areas of health care—in preventive medicine
in both individuals and the population, in screening
and diagnosis, in therapeutic interventions (whether
drugsareusedornot),
treatment—we need information about all the effects,
both beneficial and harmful, of the relevant inter-
ventions, effective ways of gathering that information,
proper reporting and effective indexing in databases,
and analysis and integration of all this information.
And we need people from different disciplines to
work together to obtain it. Armed in this way,
healthcare professionals should be able to offer their
patients a more balanced view of therapeutic benefits
and harms and more realistic explanations of what
treatments have to offer, generating more active and
trusting relationships; and governments and health-
care authorities should be able to make better
decisions about choosing strategies to improve public
health.
People trust healthcare professionals to make
balanceddecisionsonhealthcare
individual and community levels. We are expected to
recovery10; albuminfor
andinmonitoring
issuesatthe
Saturday 3 July 2004
BMJ
BMJ 2004;329:1–2
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harness reliable evidence, competent expertise, and
sensible judgments to inform our decisions, but
evidence may be biased or unavailable, and many
decisions rely on pious hopes that things will turn out
well. Some of the problems and the ways forward are
discussed in this theme issue. Have a nice trip.
Luis Gabriel Cuervo clinical editor BMJ Knowledge
BMA House, London WC1H 9JR
(lgcuervo@bmjgroup.com)
Jeffrey K Aronson reader in clinical pharmacology
University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE
(jeffrey.aronson@clinpharm.ox.ac.uk)
Competing interests: LGC has been reimbursed by BMJ Knowl-
edge, WHO, and MediLegis for participating in meetings and
conferences related to evidence based medicine; he is a
contributor to the Cochrane Collaboration, and an employee of
BMJ Knowledge, a division of BMJ Publishing Group dedicated
to evidence based publications.
1Harrabin R, Coote A, Allen, J. Health in the news.Risk,reporting and media
influence. London: King’s Fund, 2003.
Nantulya VM, Reich MR. The neglected epidemic: road traffic injuries in
developing countries. BMJ 2002;324:1139-41.
Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, et al.
Adverse drug reactions as a cause of admission to hospital. BMJ
2004;329:15-9.
Scott D, Smith C, Lohmander S, Chard J. Osteoarthritis. Clin Evid
2004;(11):1560-88.
Bigby M,Gibbs S,Harvey I,Sterling J.Warts.Clin Evid 2004;(11):2209-23.
Browning G. Wax in ear. Clin Evid 2004;(11):735-42.
Lozano JM. Bronchiolitis. Clin Evid 2004;(11):360-74.
Gupta JK, Hofmeyr GJ. Position for women during second stage of
labour. Cochrane Database Syst Rev 2004;(1):CD002006.
Silverman WA. Retrolental fibrodisplasia. Retinopathy of prematurity. New
York: Grune and Straton, 1980.
10 Van Tulder M, Koes B. Low back pain and sciatica: acute. Clin Evid
2004;(11):1500-15.
11 Alderson P,Bunn F,Lefebvre C,Li WP,Li L,Roberts I,et al.Human albu-
min solution for resuscitation and volume expansion in critically ill
patients. Cochrane Database Syst Rev 2002;(2):CD001208.
12 Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary
report: effect of encainide and flecainide on mortality in a randomized
trial of arrhythmia suppression after myocardial infarction. N Engl J Med
1989;321:406-12.
13 Hodnett ED, Gates S, Hofmeyr GJ, Sakala C. Continuous support for
women during childbirth.Cochrane Database Syst Rev 2003;(3):CD003766.
14 Klevens J, Sadowski L. Domestic violence towards women. Clin Evid
2004;(11):2358-69.
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Benefits and harms of drug treatments
Observational studies and randomised trials should learn from each other
H
apart. The movement that is subsumed under the
banner of evidence based medicine, with its sister
movements such as the Cochrane Collaboration or
the BMJ’s Clinical Evidence, aims to evaluate whether
the benefits of treatments that had been hoped for
actually exist. This relies almost exclusively on
randomised controlled trials, in particular in the study
of drug interventions. In a world apart is the field of
pharmacoepidemiology, devoting itself mainly to
detection and systematic studies of the adverse effects
of the very same treatments. Adverse drug effects are
often unanticipated and are predominantly investi-
gated by observational studies—for example, by using
large databases that link routine prescriptions with the
occurrence of unexpected disease.
The protagonists of these fields barely know each
other: they publish in different journals, write and read
different books, and work in different departments.
They are even suspicious of each other’s methods.
Adepts of evidence based medicine doubt whether
anything reasonable can follow from observational
research;they give the impression that they believe that
methods of observational research lag far behind.
Pharmacoepidemiologists have hitherto made little
use of systematic reviews of randomised trials in their
much broader job of assessing causation of harm from
a variety of pharmacological, clinical, and observa-
tional data.
Yet intellectually, both sides can and should coexist
and learn from each other.1
effects of treatment will always need randomised trials
as its yardstick. At the other end of the research
spectrum of all fields of observational research,
owever international medical science has
become, communicating electronically at the
speed of light, some fields are still worlds
w1Assessment of small
research into adverse effects of drugs offers the best
chances of being as unbiased as if randomised.2 3Each
medical question should be approached by using the
appropriate research tools4—this effectively precludes
the idea of a single grading of levels of evidence for all
types of research questions.2
Individual randomised controlled trials often do
not suffice to detect adverse effects, especially if the
effects are rare and late.5
randomised trials have offered little solace so far, even
for early and relatively common adverse effects, as
adverse events had not been systematically described
in similar ways in the individual trials and therefore
could not be compared directly for the purpose of a
systematic review.6In addition, most systematic reviews
shun observational research. Although there are
exceptions,w3-w5even established adverse effects are
often not assessed in systematic reviews, presumably
because no randomised evidence exists. However, a
balance of benefits and harms is the only reasonable
way to evaluate interventions.
Randomised trials are good at sorting out what
works and what doesn’t. Even if they show a benefit,
they often do not give sufficient insight into harms. A
properly balanced review should include a systematic
evaluation of adverse effects by the best methods of
observational pharmacoepidemiology. For their part,
pharmacoepidemiologists
exclusive preoccupation with one side of the question
and one type of methods: they should explore collabo-
ration with people who conduct systematic reviews or
randomised trials. Hidden nuggets might be found by
scraping the randomised barrel, as happened in a
w2Systematic reviews of
shouldabandontheir
Additional references w1-w6 are on bmj.com
Editorials
BMJ 2004;329:2–3
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