The treatment paradox
BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39454.622824.94 (Published 10 January 2008) Cite this as: BMJ 2008;336:100All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
The true benefit of statins is actually much less than Des Spence
outlines. This is mainly because the use of the term NNT is inappropriate,
as the 'T' suggests treatment/cure. Statins do not treat/cure death, they
only delay it.
For how long is that death delayed? There is not enough room in a
rapid response to do the maths. However, if you model the Kaplan Meier
survival curves, it is considerably less than one year. However, for the
sake of arguement, let us assume that you do gain one entire extra year of
life for every 700 years of taking a statin. Then, clearly, if you treat
for 700 years you will create one added life year.
Using this (over-optimistic) figure this means that if you treated
someone for 30 years you can expect to provide them with 30/700 added
years of life. This is 15.64 days, or, a shade over two weeks.
In short, if a fifty year old man asked you how much longer he could
expect to live if he took a statin for thiry years you can inform him
'just over two weeks - max.'
Competing interests:
I wrote the book 'The Great Cholesterol Con.'
Competing interests: No competing interests
I think that Des Spence is right when writing that the majority of
patients taking statins get no health benefit.
In the case of statins the benefit is not to get a cerebrovascular
accident or a myocardial infarction (fatal or not) i.e. the usual
endpoints in statin clinical trials. This benefit cannot diffuse.
Therefore for every NNT+1 patients taking statins for a number of
years, only one gets this benefit. The rest get practically nothing.
Competing interests:
None declared
Competing interests: No competing interests
In his article, Spence states "...an individual patient, despite many
years of investment in taking statins, gets virtually nil health benefit."
Not necessarily. Clinical trials cannot determine if the benefit is
confined to a few individuals, or distributed amongst many. Statins might
prevent (or delay) cardiovascular death in a handful of those who take
them, or they might slightly reduce the risk in everyone who takes them.
To use an analogy, wearing thermal underwear in winter might prevent
death due to hypothermia in only a few, but the benefit of keeping warm
would be felt by many.
No conflict of interest is declared, as I do not take statins or wear
thermal underwear.
Competing interests:
None declared
Competing interests: No competing interests
How right Des Spence is - the marginal individual benefits of much
modern medicine appeal only to Population-doctors, and left the individual
patient behind years ago, when we started treating 'mild hypertension' (
with an NNT of 800).
With such an NNT, and a life expectancy of 20 years .. how many of us
will be eating 'Pills in the sky, in the sweet buy-and-bye' (to paraphrase
the American workingman's hymn) ?
May I again propose this new statistic, PILL-IN-THE-SKY, representing
the total cost of treatment taken by those who will not benefit, to rank
alongside Numbers-needed-totreat and Numbers-needed-to-harm ?
Competing interests:
cost vs. benefit
Competing interests: No competing interests
Seth Jenkinson and I have got an article on a similar theme to this
piece in this month's
(http://student.bmj.com/issues/08/01/education/026.php) student BMJ.
(Interpreting the Evidence Jan 2008)
For us the key point is that any trial generates four summary
numbers. These are relative risk reduction, absolute risk reduction,
number needed to treat and personal probability of benefit.
Each number is useful, and gives some information, but no one number
gives us the whole truth about the information. Using one figure on its
own, particularly the relative risk reduction above all others, is very
risky.
Each figure takes a different viewpoint on the evidence. The relative
risk reduction is a public health (area wide) prediction.
The absolute risk reduction puts the starting risk back into the
frame.
The number needed to treat measures the workload needed to achieve
the relative risk reduction. It's the beginning of health economics.
The personal probability of benefit answers the patient's question,
"what's in this for me?"
All the figures are contained in every clinical trial, and they each
give very different perspectives on the risks and benefits of treatment. I
would ask that all be reported in each clinical trial, and then an overall
assessment of benefit can be made, with clarity about which perspective is
being used.
http://student.bmj.com/issues/08/01/education/026.php
Competing interests:
None declared
Competing interests: No competing interests
Statistics, limiting factors, and the Future
There is not an absolute standard which can be used to assess the
performance of a drug or medical technology. Clinical trials are only as
good as is reasonably practicable. The number of variables which can
affect the outcomes of clinical studies is far too great for such studies
to claim to be absolute and beyond dispute. The statistics used to
evaluate a drug’s performance can be presented in a multitude of ways. It
is for these reasons that pharmaceutical companies select the clinical
studies which most appropriately support their aims which is to gain
marketing authorisation for a drug. Clinical trials do not have the
primary aim of proving the safety of a drug. They are part of the process
with which a pharmaceutical company has to comply to get their products
approved for use. This is an important distinction the implications of
which should be considered when noting the numbers of drugs which have
been withdrawn from use after having been authorized for use by regulators
i.e. after approval when side-effects arise. Perhaps, as seems likely,
there is no such thing as a safe drug i.e. that, due to the complex nature
of the body's physiological systems 6, any drug acting upon a biochemical
sequence will inevitably affect the stability of all other systems, organs
and biochemical sequences.
Western medicine is increasingly based upon an evidence-based
approach however any form of clinical trial or scientific evaluation is
based upon the prevailing state of knowledge and hence is open to abuse.
It is quite surprising when filtering medical research papers to
understand the limitations of the medical profession e.g. (1) 80% of what
is practiced by a doctor is not evidence-based 1, (2) a doctor's ability
to make a medical diagnosis ranges between 20-80% depending upon the
condition 2,3 the reporting journal, the quality of the doctor, the time
of the consultation, etc (3) circa 90% of drugs are ineffective in circa
50% of the population 4, (4) as little as 1-2 % of clinical trial
applicants are subsequently enrolled in clinical trials 5 (5) c15% of
drugs are prescribed for applications for which they are not approved, and
(6) there is not a widely accepted theory for the origins of the current
plethora of illnesses affecting life in western societies. These issues
and many more illustrate that there are very significant knowledge-
deficits pertaining to the current level understanding of the body's
function and hence the ability to diagnose and treat a wide range of
medical conditions.
Complementary medicine is based upon a wide range of phenomena which
conventional medicine has chosen to overlook. It is based upon the dynamic
inter-relationship between our sensory input and our biochemistry, our
mind and our body, our psychology and our physiology. In the same way that
medical researchers have understood how the body reacts to x-rays,
positron-emission, ultrasound, and have used such phenomena with
diagnostic and therapeutic effect similarly the understanding of other
phenomenae will lead to the development of new medical technologies 7 with
diagnostic and therapeutic capabilities. Any attempts to prohibit the use
of complementary or alternative medicines or technologies are effectively
seeking to stifle research into their principles.
New knowledge in areas traditional considered to be the realm of
psychology or complementary medicine leads to new medical findings which
has diagnostic and therapeutic implications. The Russian researcher Dr
I.G.Grakov has developed a cognitive-based technology which is able to
mathematically model the consequences of cognition and hence to provide a
health report of a seemingly unimaginable level of sophistication e.g. to
diagnose (1) the psychological profile(2) the level of stability of the
physiological systems (3) the level of stability of each organ (4) the
precise medical conditions affecting each of c30 organs in the body and
(5) the morphology of each organ (claimed to be up to 25% more accurate
than conventional diagnostic techniques). Furthermore this principle,
applied in reverse, leads to a light-based therapy which appears able to
treat the psychosomatic components of illness (claimed efficacy 93%). This
technology is now used in the Russian Health Services where each day circa
3,000 GPs, psychologists, neurologists, radiologists, etc; send patient
reports for processing by the remote computer server.
Homeopathy is another phenomena where the principles have not yet
been fully understood 9 (at least by western researchers) and hence is
subject to criticism by medical sceptics yet the Russian company MATERIA
MEDICA 8 has established a 'homeopathic technology' which isolates the
antibodies which have been are produced in the body arising from the use
of homeopathic remedies. These 'polyclonal antibodies' are subsequently
manufactured using proprietary technology and are currently being used in
pharmaceutical products which are being sold on the Russian market.
Moreover these antibodies are being produced for Materia Medica by a
contract manufacturer in the UK! Furthermore the study of these polyclonal
antibodies is now an area of research for pharmaceutical companies
including GSK, Serologicals and PPL Therapeutics. Perhaps the academic
debate has now being overtaken by events!
Such information appears to support the claims for and hence the
continued use of homeopathy but may also highlight the limitations of
practitioners - practitioners are human and humans make mistakes. It also
appears to reduce the use of homeopathy and of homeopathic antibodies to
the same one-size-fits-all approach adopted by the pharmaceutical
industry.
There are lies, damned lies and statistics. Believe what you wish to
believe. Does the current level of debate assist technological progress?
Graham Ewing, Montague Healthcare
References
1. comments attributed to Dr Graham Archard, Royal College of General
Practitioners speaking at The Science and Art of Healing Conference held
at the Royal College of Physicians, London, September 2007
2. articles featured in the Lancet, Mayo Clinic and in The. British
Medical Journal 18th March, 2000.
3. www.wrongdiagnosis.com/intro/common.htm; National Patient Safety
Foundation, phone survey 1997
4. comments attributed to Professor Allan Roses, Vice-President of
Pharmacogenetics, GSK, speaking at a medical symposium in London, December
2003. http://www.ahrp.org/infomail/03/12/08.php;
http://www.bmj.com/cgi/eletters/330/7502/1262
5. comments attributed to Dr Irving Kirsch, University of Hull
speaking at The Science and Art of Healing Conference held at the Royal
College of Physicians, London, September 2007
6. Merck Manual pages 3-5
7. Virtual Scanning - a new generation of healthcare - beyond
biomedicine? ISBN no 978-0-9556213-0-7. Authors Elena Ewing (Dr) and
Graham Ewing B.Sc
8. http://www.angelbio.com/news.asp?id=123;
http://www.materiamed.com/info.php?rid=112
9. Benefits and risks of homeopathy (Comment), Lancet 370, 9600 (Nov 17),
1672-3 by Goldacre.B
Competing interests:
co-author of the book ‘Virtual Scanning – a new generation of healthcare – beyond biomedicine?’.
Competing interests: No competing interests