Andy Grieve, Executive Director

1
Statistics and Its Place in the Evolution of
Medicine as an Evidence-Based Science

• Andy Grieve, Executive Director
• Statistical Research Consulting Centre
• Pfizer Global RD, Sandwich

2
Outline

• Statistical Evidence is Everywhere
• What is meant by Evidence-Based
• Quantification in 18th Century British Medicine
• The Méthode Numérique of Louis (19th Century
  France)
• Radickes Method (19th Century Germany)
• Karl Pearson and Typhoid Fever (Early 20th
  Century Britain)
• Comparisons to Modern Evidence-based Medicine

3
Statistics are Everywhere

• .. statistics .. is a mechanism for trying to
  understand and explain what is going on in
  society using measurement. It can be used in
  every social aspect of society, every aspect of
  the physical sciences, in any area of study. It
  is the means of elucidating, rather than
  obfuscating, what is really going on around us.
• Charles Clarke, Secretary of State for Education,
  on opening RSS 2004, Manchester, 7 September

4
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.

5
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.
• Charities use statistics to relieve us of our
  money.

6
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.
• Charities use statistics to relieve us of our
  money.
• Politicians use statistics to persuade us that
  they understand society's ills and that they
  deserve our support to solve them.

7
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.
• Charities use statistics to relieve us of our
  money.
• Politicians use statistics to persuade us that
  they understand society's ills and that they
  deserve our support to solve them.
• Newspapers, television and radio use statistics
  to spice up their reports to make them more
  dramatic, more convincing, more compelling.

8
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.
• Charities use statistics to relieve us of our
  money.
• Politicians use statistics to persuade us that
  thy understand society's ills and that they
  deserve our support to solve them.
• Newspapers, television and radio use statistics
  to spice up their reports to make them more
  dramatic, more convincing, more compelling.

• Companies use statistics to advertise their
  products.

2 Out of 3 Dentists Surveyed Prefer
Crest Ivory Soap is 99.9 Pure Pall Mall
gives you More Puffs than the other Major Brands
(Based on Avg. Puffs per Cigarette)
9
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.
• Charities use statistics to relieve us of our
  money.
• Politicians use statistics to persuade us that
  thy understand society's ills and that they
  deserve our support to solve them.
• Newspapers, television and radio use statistics
  to spice up their reports to make them more
  dramatic, more convincing, more compelling.

• Companies use statistics to advertise their
  products.
• Scientists use statistics to document their
  findings and support their conclusions.

10
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.
• Charities use statistics to relieve us of our
  money.
• Politicians use statistics to persuade us that
  thy understand society's ills and that they
  deserve our support to solve them.
• Newspapers, television and radio use statistics
  to spice up their reports to make them more
  dramatic, more convincing, more compelling.

• Companies use statistics to advertise their
  products.
• Scientists use statistics to document their
  findings and support their conclusions.
• Statistics are used in all forms of sport

11
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.
• Charities use statistics to relieve us of our
  money.
• Politicians use statistics to persuade us that
  thy understand society's ills and that they
  deserve our support to solve them.
• Newspapers, television and radio use statistics
  to spice up their reports to make them more
  dramatic, more convincing, more compelling.

• Companies use statistics to advertise their
  products.
• Scientists use statistics to document their
  findings and support their conclusions.
• Statistics are used in all forms of sport
• Those with whom we agree use statistics to
  reassure us that we're on the right side

12
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.
• Charities use statistics to relieve us of our
  money.
• Politicians use statistics to persuade us that
  thy understand society's ills and that they
  deserve our support to solve them.
• Newspapers, television and radio use statistics
  to spice up their reports to make them more
  dramatic, more convincing, more compelling.

• Companies use statistics to advertise their
  products.
• Scientists use statistics to document their
  findings and support their conclusions.
• Statistics are used in all forms of sport
• Those with whom we agree use statistics to
  reassure us that we're on the right side,
• While our opponents use statistics to try and
  convince us that we are wrong.

13
Statistics are Everywhere.

• Social reformers use them to convince us that
  social problems are serious and deserve our
  attention and concern.
• Charities use statistics to relieve us of our
  money.
• Politicians use statistics to persuade us that
  thy understand society's ills and that they
  deserve our support to solve them.
• Newspapers, television and radio use statistics
  to spice up their reports to make them more
  dramatic, more convincing, more compelling.

• Companies use statistics to advertise their
  products.
• Scientists use statistics to document their
  findings and support their conclusions.
• Statistics are used in all forms of sport
• Those with whom we agree use statistics to
  reassure us that we're on the right side,
• While our opponents use statistics to try and
  convince us that we are wrong.
• Statistics are one of the standard types of
  evidence used by people in our society.

14
Evidence-Based Society

• Professor Adrian Smith Royal Statistical
  Society Presidential Address 1996 - Mad Cows and
  Ecstasy Chance and Choice in an Evidence-Based
  Society
• , in which informed quantitative reasoning is
  the dominant modality in public debate, as well
  as in the decision-making processes of
  government, business and individuals
• As well as "evidence based medicine ..
  management", I sometimes enter discussions of
  " evidence based" chemistry, metallurgy,
  cosmology, geology, sociology ... and more

15
Evidence-Based Medicine

• 1992 Journal of the American Medical Association
  published a manifesto
• A new paradigm for medical practice is
  emerging. Evidence-based medicine de-emphasises
  intuition, unsystematic clinical experience and
  patho-physiological rationale as sufficient
  grounds for clinical decision-making and stresses
  the examination of the evidence from clinical
  research

16
3 Classic Cultures to Determine Medical Evidence

• systemic-pathophysiological

• modern laboratory science, the Hippocratic,
  galenic systems as well as more modern movements
  such as homeopathy (Hahnemann) and anthroposphy
  (Steiner)

Dominant since antiquity

• individual cases / medical judgement

• individual-clinical

• Collection of empirical evidence

• statistico-analytic

• Hippocrates 1st aphorism experiment and
  experience treacherous
• A doctor did not test, he or she knew
• Perform all these duties calmly and adroitly,
  concealing most things from the patientGive
  necessary orders with cheerfulness and serenity,
  turning his attention away from what is being
  done to him sometimes reprove sharply and
  emphatically.revealing nothing of the patient's
  future of present condition

• The introduction of the empirical approach in
  medicine was largely an 18th century British
  initiative its most famous proponent James
  Lind

17
James Lind and the treatment of scurvy
18
James Linds Experiment (1747)

• Scurvy killed more sailors than military action
• Experiment performed on navy ship
• On the 20th May 1747 Lind took 12 patients as
  similar as I could have them. They all in general
  had putrid gums, the spots and lassitude, with
  weakness of their knees.
• 2 each to one of 6 treatments all of which were
  justified by dogma or ordinary experience
• Standard diet
• water gruel sweetened with sugar in the morning
  fresh mutton broth often times for dinner at
  other times puddings, boiled biscuit with sugar
  etc. and for supper barley, raisins, rice and
  currants, sago and wine, or the like.
• A diet almost guaranteed to cause scurvy !!!

19
James Linds Experiment (1747)

• Two a quart of cyder a day
• Two otherstwenty five gutts of elixir vitriol
  three times a day upon an empty stomach, using a
  gargle strongly acidulated with it for their
  mouths
• Two others.two spoonfuls of vinegar three times
  a day upon an empty stomach, having their gruels
  and their other food well acidulated with it, as
  also the gargle for the mouth
• Two of the worst patients, with the tendons in
  the ham rigid (a symptom none the rest had) were
  put under a course of sea water. Of this they
  drank half a pint every day and sometimes more or
  less as it operated by way of gentle physic
• Two others had each two oranges and one lemon
  given them every day. These they eat with
  greediness at different times upon an empty
  stomach. They continued but six days under this
  course, having consumed the quantity that could
  be spared
• The two remaining .bigness of a nutmeg three
  times a day of an electuray recommended by an
  hospital surgeon made of garlic, mustard seed,
  rad. raphan., balsam of Peru and gum myrrh, using
  for common drink barley water well acidulated
  with tamarinds, by a decoction of which, with the
  addition of cremor tartar, they were gently
  purged three or four times during the course

20
James Linds Experiment (1747)

• The consequence was that the most sudden and
  visible good effects were perceived from the use
  of the oranges and lemons one of those who had
  taken them being at the end of six days fit four
  duty. The spots were not indeed at that time
  quite off his body, nor his gums sound but
  without any other medicine than a gargarism or
  elixir of vitriol he became quite healthy before
  we came into Plymouth, which was on the 16th
  June. The other was the best recovered of any in
  his condition, and being now deemed pretty well
  was appointed nurse to the rest of the sick
• The next best treatment was cider as had been
  shown previously in a large comparative trial.
• The other treatments had no positive effect !

21
James Linds Experiment (1747)

• Lind believed in empiricism because
• He understood the role of imagination and
  suggestion in healing
• An important lesson in physic is here to be
  learnt, viz. The wonderful and powerful influence
  of the passions of the mind upon the state and
  disorders of the body. This is often overlooked
  in the cure of diseases
• Postulated that all observations from a series of
  unselected cases rather than the habit of
  publishing individual successful cases only
  should yield the evidence for therapeutic
  recommendations
• He was identifying selection bias, observer
  bias, publication bias

22
18th Century Britain

• Lind was not alone
• He was one of a relatively large number of
  medical graduates (particularly from Edinburgh
  University)
• They were characterised by
• being outside the medical establishment
• using quantitative measurement to challenge dogma
  based on theory
• non-conformists, Unitarians
• Formed medical societies which tended to be
  regional
• One influential, regional, group formed in
  Warrington as an epicentre of Manchester,
  Liverpool and Chester

23
The Warrington Group
Conducted controlled experiments in the treatment
of rheumatism
Argued for recording of serial data successes
failures to avoid false conclusions if he
trusted to memory alone
Observations on Amputations (1779) operated in
25 cases, such as promiscuously occurred at the
Liverpool Infirmary, without the loss of a single
patient
Thomas Percival 1764
John Haygarth 1765
Corresponded with Richard Price about using bills
of mortality as a data bank useful for clinical
research.
Investigation of cold water bathing for fever. He
collected body temperatures to measure
effectiveness
Quantitative evaluation of his practice of
cleanliness and ventilation in Manchester as
prophylaxis against puerperal sepsis
24
18th Century Britain

• The methods they used were termed medical
  arithmetic unsophisticated
• In therapeutics the arithmetic observationists
  tests would involve mathematically the formation
  of sums, the calculation of averages (I.e.
  arithmetic means), and at highest, that of ratios
  (e.g.. Success-to-failure ratios (Tröhler ,
  1978)

25
Monograph Published by Royal College of
Physicians of Edinburgh Based on his 1978 UCL PhD
26
Basis of Argumentation in Medical Periodicals
(1733-1829)
0.7
0.6
0.5
0.4
Percent of Articles
0.3
Journal
0.2
0.1
0
One case
Two cases
gt Two cases
Other Articles
Type of Article
Source Ulrich Tröhler PhD Thesis, UCL, 1978
27
Other examples in Tröhler of Medical Arithmetic

• The removal of bladder stones without killing
  patients
• Adopting a folk remedy for Dropsy
• The treatment of rheumatism
• Improving survival after amputation
• Treating Syphilis with mercury
• Treating fever with Peruvian bark (quinine)

28
Bladder Stones Lithotomy

• Bladder stones much more common in 18th century
• Diet, urinary infections, elderly men hypertrophy
  of the prostate
• Celsus in the 1st century
• Stone pulled down per rectum into the perineum.
  Once localised under the skin, in the previously
  dilated part of the urethra a cut was made
  directly to the stone.
• The early lithotomists were itinerant, largely
  self-trained
• Pain extremely severe worth the risk of an
  operation
• High mortality
• Successful lithotomists used simple statistics
  to maintain their reputations and stay in
  business.
• Friar Jacques, in Paris, William Cheselden in
  London
• Developed methods for cutting directly into the
  bladder
• Speed, convenience, greater success rate

29
Bladder Stones Lithotomy

• William Cheselden Anatomy (1740)
• Keen to show the truthfulness of his data
• I cannot take the liberty to mention the names
  of private patients, therefore I will give a
  detail of those only which I cut in the hospital,
  where the first 25 recovered, to the truth of
  everyone of which I had above 20 witnesses, and I
  do believe these patients are all living at this
  time
• Comparison (tabulation) of mortality rates by age

• Investigations of the influence of gender, weight
  of stone
• Investigations of time to death and recovery

30
Digitalis and Dropsy

• William Withering Account of the Foxglove
  (1785)
• He was recommended the foxglove to treat dropsy
  (oedema) by an old countrywoman
• He undertook a prospective study lasting 15
  years before he was prepared to publish 163
  patients (156 from private practise)
• It would have been an easy task to have given
  select cases, whose successful treatment would
  have spoken strongly in favour of the medicine,
  and perhaps been flattering to my own reputation.
  But Truth and Science would condemn the
  procedure, I have therefore mentioned every case
  . Proper or improper, successful or otherwise
• Quality of data Withering only used his own
  data because it might be misleading if the other
  publications did not give all the relevant
  details, failures as well as successes.

31
The Treatment of Rheumatism

• John Haygarth The Imagination as a Cause and as
  a Cure of Disorders of the Body (1800)
• Trial of Perkins Metallic Tractors
• These were metallic rods supposed to cure
  rheumatism by electrical/magnetic influence

• It was fashionable Institute of Perkinism in
  London
• Haygarths Experiment in two parts
• Wooden imitation tractors used (without their
  knowledge) on 5 patients 1/5 were relieved.
• The next day genuine tractors resulted in 1/5
  patients being relieved
• Single-blind, placebo controlled ??

32
The Statistics of Amputation

• Edward Alanson Practical Observations on
  Amputations (1779)
• Alanson developed an improved amputation
  technique since using his new method he had
  operated on thirty-five cases, .without the
  loss of a single patient
• Prior to the this new method Alanson had been
  present at 46 amputations of whom 10 patients had
  died
• Historic control data ?
• He had never refused to operate upon any case
  that has presented, where a single person in
  consultation has thought such an operation
  advisable
• Selection bias ?

33
France Beginning of the 19th century

• 3 different visions of the physician
• The artist
• Professor Risueno dAmador promoted the vision
  of the physician as an artist,relying on medical
  tact and his intuition about the individual
  patient
• The statistician
• Pierre-Charles-Alexandre Louis had little
  respect for tact and wanted to see the evidence
• The determinist
• Claude Bernard a physiologist reject both the
  artist and statistician views. Science was
  certainty.

A great surgeon performs operations for kidney
stone by a single method later he makes a
statistical summary of deaths and recoveries, and
he concluded from these statistics that the
mortality law for this operation is two out of
five. Well, I say that this ratio means literally
nothing scientifically and gives us no certainty
in performing the next operation
34
PCA Louis and the Méthode Numérique
35
PCA Louis and the Méthode Numérique

• Medical doctor graduated 1813
• Most famous work (1823) on blood-letting and
  pneumonia
• Introduced the idea of the Méthode Numérique
  for deciding whether treatments were effective
• Méthode Numérique comparison of means

36
Data from Louis (1835) - Effect of Blood letting
in surviving patients with pneumonia Duration
of disease (d days), number of bleeds (n),
Related to Time of First Bleed (days)
37

Data from Louis (1835) - Effect of Blood letting
in surviving patients with pneumonia Duration
of disease (d days), number of bleeds (n),
Related to Time of First Bleed (days)
50
40
Duration of Disease (Days)
30
20
10
0
1
2
3
4
5
6
7
8
9
Time of First Bleed (Days)
38
Data from Louis (1835) - Effect of Blood letting
in surviving patients with pneumonia Duration
of disease (d days), number of bleeds (n),
Related to Time of First Bleed (days)

• Professor Peter Armitage Royal Statistical
  Society Presidential Address 1983 Trials and
  Errors The Emergence of Clinical Statistics
• Analysed the data
• 1. Overall no difference between the 9 groups
• 2. Contrast 1-4 versus 5-9 not significant
  (p0.038)
• 3. Contrast 1-2 versus 3-9 significant
  (p0.006)
• Such modern analyses depend on understanding the
  variability of the data

39
Gustav Radicke and Understanding
Variation(Henrik Støvring, The Statistician ,
1999)
40
Radickes Proposals (1858)

• Considered different types of means
• arithmetic, geometric, harmonic and quadratic
  mean
• Chose the arithmetic mean
• as the probable value of a variable quantity
  determined under mean conditions
• Relevance to nearly all medical applications
• Even under stable conditions the biological
  responses of an individual vary
• Measurement error, biological variation
• Effect of salt on the excretion of urine

41
Radickes Proposals (1858)

• Remember Louis only looked at means
• Radicke pointed out the need to consider
  variability
• Three methods
• Suppose we have values xij (i1, , n j1, ..
  , 2)
• Absolute variation
• a Maximum xij - mj m1 - m2 gt 2a
• Fluctuation of Successive Means
• a Maximum difference between cumulative
  means(mean of the first i observations) and mj
  then follow 1.
• Mean Error (Quadratic Mean)
• Standard deviation within each group sj m1 -
  m2 gt 2(s1 s2 )

42
Data from Kaupp (1855)Total Urinary Excretion -
Volume

• Kaupp experimented on himself for 92 days
• observed a rigorous diet (same menu measured to
  the gram)
• constant life-style (the life of an ordinary
  student)
• Seven different doses of salt for 12 days (15
  versus 12)
• Measured daily temperature
• Missing data on 5 days measurement error and on
  one occasion he consumed 8 glasses of
  non-dietary beer !!

43
Data from Kaupp (1855)Total Urinary Excretion
Volume (cc)
33.6 g
28.7 g
19.0 g
14.2 g
9.3 g
1.5 g
23.9 g
Dose Of Salt
3000
2800
2600
2400
Volume
2200
2000
1800
1600
0
20
40
60
80
100
Time
Missing data simulated by Støvring from a Normal
density with m and s2 estimated from the
complete data
44
Data from Kaupp (1855)Total Urinary Excretion
Urea (gm)
33.6 g
28.7 g
19.0 g
14.2 g
9.3 g
1.5 g
23.9 g
Dose Of Salt
Missing data simulated by Støvring from a Normal
density with m and s2 estimated from the
complete data
45
Data from Kaupp (1855)Total Urinary Excretion
Volume ACF
46
Data from Kaupp (1855)Total Urinary Excretion
Vol/Temperature

• Accounting for temperature
• Modern approach is to use analysis of covariance
• Kaupps proposals were attempts to estimate
  linear relationship by grouping

47
Data from Kaupp (1855)Total Urinary Excretion
Vol/Temperature

• Accounting for temperature
• Modern approach is to use analysis of covariance
• Kaupps proposals were attempts to estimate
  linear relationship by grouping (linearity
  questioned by Radicke)

• Adjusting urinary excretion data for different
  temperatures before applying previous procedure
• Conclusion no evidence of influence of salt
  and/or temperature
• Not supported by modern analysis

48
Karl Pearson Almoth Wrightand typhoid
inoculation
49
Almoth Wright Typhoid Inoculation

• 1892 made Professor of Pathology at the
  Royal Army Medical College in Netley
• Developed prophylactic immunization against
  typhoid
• Tested it on himself, friends and students
• 1904 published A Short Treatise on Anti-Typhoid
  Inoculation
• cogency of statistical evidence
• existence of a control group
• exact recording of all data
• Generally more advisable for the physician to
  accept the general conclusions implied by the
  statistics rather than to worry excessively about
  the theoretical underpinnings

50
Karl Pearson Typhoid Inoculation

• Pearson approached by War Office
• Could he establish whether Wrights
• results were significant ?
• Pearson suggested a prospective clinical trial
• Not taken up
• But he did analyse the available data
• Pearson published his work in the BMJ in Nov. 1904

Karl Pearson
51
Inoculation Against Typhoid Karl Pearson (BMJ,
1904)
Indian Army 1901
Indian Army 1900
7th Hussars
City Imperial Volunteers
5th Battalion Manchester Regiment
Methuens Column
Garrison Ladysmith
Army Regiments / Hospitals
Staff 2nd Sec. Scot. Red Cross Hosp
Staff No. 9 General Hosp
Staff No. 8 General Hosp
Staff Imp. Yeo Hosp Pretoria (2)
Staff Imp. Yeo Hosp Pretoria (1)
Staff Imp. Yeo Hosp Deelfontein
Staff Portland Hosp.
0.001
0.01
0.1
1
10
100
Odds Ratios and 95 Confidence Interval (log
scale)
52
Pearson BMJ, 1904

• Estimated correlation between immunity and
  inoculation (tetrachoric correlation fitting a
  bivariate normal density to a 22 table)
• Theory published in Phil. Trans. Roy. Soc. 1900
• Bayesian Integrated over parameter space
• Approximate asymptotic s.e.
• He thought of the data that would convince him of
  the efficacy of the vaccine.
• Before working out the data, the impression
  formed in my mind was that if the correlations
  turned out to be fairly consistent and greater
  than 0.4, we might consider the case for
  inoculation proven if irregular and less than
  0.2 unproven that is, it must be a very small
  value, possibly more than balanced by concomitant
  ills while, if lying between 0.2 and 0.4,
  further cautious investigation by experimental
  inoculation seemed desirable
• He based numerical values on the known
  effective smallpox vaccine.
• Strong evidence 0.2 corresponds to an OR of
  0.5 (2) and 0.4 to an OR of 0.2 (5)

53
Pearsons Enteric Fever DataBy Grouping Log
Odds ratios Pearsons approach
?
?
?
Indian Army
?
?
?
Hospital Staffs
?
Arithmetic Mean
0.01
0.1
10
1
Odds Ratios and 95 Confidence Interval (log
scale)
54
BMJ 1904

• He concluded the results although statistically
  significant, they were irregular and the
  lowness of the values suggested environmental
  factors were influential.
• Advocated suspension of the operation as a
  routine method and further study

55
Pearsons Enteric Fever DataBy Grouping Log
Odds ratios Modern approach
?
?
?
Indian Army
?
?
?
Single Regiments
?
?
?
Methuens Column
Ladysmith Garrison
?
?
?
?
?
?
Random Effect Model
Hospital Staffs
?
?
?
Fixed Effect Model
?
?
?
0.1
10
0.01
1
Odds Ratios and 95 Confidence Interval (log
scale)
56
Wright versus Pearson

• Editors of BMJ agreed with Pearson vs. Wright
• They regretted that a newspaper of such
  influence as the Times had come out in favour of
  Wrights position in an attempt to
• force on the War Office and on the army a
  method which, on the testimony of its author,
  requires the labour of years to perfect, and the
  use of which involves possibilities of serious
  mischief
• Wright
• Pearsons mathematical principles were unerring
  and beyond my intellectual ken
• The advisory board were hiding behind Professor
  Pearsons petticoats in their attempt to keep
  anti-typhoid inoculation from being introduced.
• Pearson
• There was a crying need for a more exact
  treatment of statistics in medical science

57
Modern Evidence-Based Medicine
58
Evidence-Based Medicine

• Evidence-based medicine is the conscientious,
  explicit, and judicious use of current best
  evidence in making decisions about the care of
  individual patients. The practice of
  evidence-based means integrating individual
  clinical experience with the best available
  external clinical evidence from systematic
  research . Without current best evidence,
  practice risks becoming rapidly out of date, to
  the detriment of patients
• Sackett et al (1996), British Medical Journal

59
Evidence-Based Medicine

• Requires
• Identification of Evidence
• Establishment of the Quality of the evidence
• Individual cases
• Non-controlled studies
• case-control studies (retrospective)
• randomised controlled studies
• double-blind, randomised controlled studies
• Synthesis of the Evidence
• Meta-Analysis

60
Book Review Nature 392, 671 - 672 (16 April 1998)

• A new kind of alchemy is abroad in the world.
  Arcane, esoteric and mesmerizing, it promises not
  to turn base metal into gold, nor to provide an
  elixir of youth, but to transmute statistical
  sows' ears into scientific silk purses.
  Meta-analysis, the systematic synthesis of
  otherwise inconclusive research findings into
  hard results, has, in the space of barely two
  decades, come from a standing start to challenge
  the blind clinical trial as the principal arbiter
  of truth and the touchstone of knowledge across a
  range of biomedical and social sciences

61
Parallels Between 18th /19th Centuries
20th/Early 21st Centuries Tröhler (2001)

• Requires
• Intense discussions about how to assemble
  reliable evidence about the effects of health
  care (league tables ?)
• An emphasis on going beyond the treatment of the
  individual (clinical guidelines ?)
• Commercialism (economic analysis)
• Allocation of scarce resources (cost of citrus
  fruit)
• Considerable medical innovation and a demand for
  comparison to standard treatment
• Empirical testing of medical interventions

62
Conclusion

• Critical statistical evaluation of medical
  interventions
• medical arithmetic 18th century Britain
• Méthode Numérique 19th century France
• Evidence-based Medicine late 20th century
• Introduction depends on the appropriate climate
• Public understanding depends on increased
  education