Kan erfaringerne med kontrollerede

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Kan erfaringerne med kontrollerede forsøg på
sundhedsområdet bruges på andre
områder? Årsmøde Dansk Evalueringsselskab 16.
september, 2006 Kjeld Møller Pedersen Syddansk
Universitet
2
Disposition

• Kort historik vedr. kontrollerede/randomiserede
  forsøg
• i sundhedssektoren
• Hvorfor er det kontrollerede forsøg så vigtigt?
• Pragmatiske forsøg også vejen i andre sektorer
• Eksempler
• Evidensbevægelsen

3

• Svar ja naturligvis!
• MEN det kræver
• ønske om at dokumentere effekt
• måske endda en ide om, at man i det godes
• navn enten direkte skader eller spilder penge
• at man forstår de nye(re) former
• for kontrollerede forsøg
• at man ikke forveksler procesevaluering
• med effektevaluering
• en ændret evalueringskultur
• m. øget videnskabelighed

4
Kort historik
5
Det startede med R.A. Fisher
1925
Statistical Methods for Research Workers,
Statistical Methods and Scientific Inference,
andThe Design of Experiments
ROTHAMSTED EXPERIMENTAL STATION,February 1925
Ideen om randomisering
6
Bradford Hill blev pioneren for randomiserede
forsøg i sundhedssektoren
He was the statistician on the Medical Research
Council Streptomycin in Tuberculosis Trials
Committee and their study evaluating the use of
streptomycin in treating tuberculosis, is
generally accepted as the first randomised
clinical trial "Medical Research Council
(1948) Streptomycin in Tuberculosis Trials
Committee. Streptomycin treatment of pulmonary
Tuberculosis. British Medical Journal, 2
769-83.
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1. Førte gradvist til, at det randomiserede
forsøg blev idealt fra 50erne og fremefter
inden for lægevidenskabelige forskning.
2. 1962 The Kefauver-Harris Drug Amendment in
the USA proof of efficacy required for new drug
approval, in addition to proof of safety. med
krav om randomiserede forsøg

• 3. 1965 EF-direktiv om afprøvning af lægemidler
  i kølvandet
• på thalidomid-skandalen
• pille solgt i 50erne og tidlige 60er som
  middel mod bl.a.
• morgensyge hos gravide
• var afprøvet i dyreforsøg men på mennesker
• mindst 15.000 i 40-lande blev født med
  forskellige
• handicap

• 4. I alle lande kræves der dokumentation for
  lægemidlers
• effektivitet før tilladelse til markedsføring
  (fase I, II og III-forsøg)
• Har været afgørende for cementeringen af det
  randomiserede
• forsøg som det ultimative design vedrørende
  effekt

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1971

• Foreslog evidenshierarki
• Senere kendt som Cochrane
• hierarkiet

Two of the most striking changes in word usage
in the last twenty years are the upgrading
of opinion and the downgrading of the word
experiment
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Ideen om det randomiserede forsøg spredte sig i
60erne til samfundsvidenskaberne
10
Efterfølgeren Shadish, Cook Campbell fra
2001
Klassikeren fra 1963

• 84 sider
• Trusler mod
• den interne validitet
• den eksterne validitet

624 sider alt der er sket siden 1963
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• Der er ni kilder til som kan true interne
  validitet
• - Og dermed om en effekt i kausal forstand
• skyldes en given intervention
• selektion
• historie (forløb af tid)
• modning
• gentagne målinger (testning)
• målemetoden
• regression mod midten
• frafald (eksperimentel moralitet)
• interaktion mellem selektion og modning
• forsøgsleder-bias
• Det randomiserede forsøg og varianter deraf
• håndterer de fleste af disse trusler

12
Hvorfor (randomiserede) forsøg
13
Det randomiserede forsøg
Kernen er ønske om så éntydigt som muligt at
etablere kausalitet en årsag-virknings-kæde -
kræver minimering af enhver form for bias
Simpleste form for randomisering

• Interventionsgruppe
• ens standardiseret behandling
• Kontrolgruppe (ikke nødvendigvis
• placebo)

inklusion
potentielle målgruppe
Andre trusler som forsøgspersoners eller
forsøgs lederes kendskab til interventionsregieme
fjernes ved blinding og dobbel blinding
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Fordel eliminerer mange trusler mod den interne
validitet Ulempe bliver let et drivhus og
ikke den køkkenhave det skulle
være - trusler mod den eksterne
validitet (generaliseringsmuli
gheder)
15
Sammenhængende problemstillinger, der kan sætte
spørgsmålstegn ved det rene randomiserede
forsøg
Intern validitet - efficacy
Ekstern validitet - generaliserbarhed
Kvalitativ- kvantitativ evidens
Implementering
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Udviklingen af det pragmtiske forsøg

• Trials of healthcare interventions are often
  described as
• either explanatory or pragmatic.
• Explanatory trials generally measure efficacy
• the benefit a treatment produces under ideal
  conditions,
• often using carefully defined subjects
  in a research clinic.
• Pragmatic trials measure effectiveness
• the benefit the treatment produces in routine
  clinical practice.

OFTE TO faser først efficacy og dernæst
effectiveness
Understanding controlled trials What are
pragmatic trials? BMJ, 1998
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Interventionen er ikke (nødvendigvis)
standardiseret
While the intervention should be described
precisely for both types of trial, in pragmatic
trials this does not mean that the same treatment
is offered to each patient. If, for example, two
physiotherapy approaches are being evaluated for
back pain the protocol may allow for the
physiotherapist to apply different treatments to
different patients it is then the management
protocol which is the subject of the
investigation, not the individual treatments.
18
OG blinding er ikke alfa-og-omega
While pragmatic trials may also be blinded, this
is not always possible. Placebos are not
generally used in pragmatic trials, as they aim
to help clinicians decide between a new treatment
and the best current treatment. Clinician and
patient biases are not necessarily viewed as
detrimental in a pragmatic trial but accepted as
part of physicians' and patients' responses to
treatment and included in the overall
assessment. In pragmatic approaches, therefore,
the treatment response is the total difference
between two treatments, including both treatment
and associated placebo effects, as this will best
reflect the likely clinical response in practice
19
Eksempel effekten på opsøgende hjemmebesøg hos
75-årige af et uddannelsesprogram resultat
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Eksempel effekten på opsøgende hjemmebesøg hos
75-årige af et uddannelsesprogram design

• intervention udannelsesforløb rettet mod
  optimering af
• af hjemmebesøgene,
  tværfaglig tilgang
• design 34 kommuner fra 4 amter, matchet i
  17 par
• lodtrækning inden for hvert par

21
Godt simpelt eksempel
Håndhygiejne og småbørnssygelighed i
daginstitutioner En interventionsundersøgelse
UFL, 1999, no. 31, (august)
22
A randomised multicentre trial of integrated
versus standard treatment for patients with a
first episode of psychotic illness (Kbh. og
Århus, BMJ, 2005
RandomisationThe included patients were
centrally randomised to integrated treatment or
standard treatment. In Copenhagen, randomisation
was carried out through centralised telephone
randomisation at the Copenhagen Trial Unit. The
allocation sequence was computer generated, 11,
in blocks of six, and stratified for each of five
centres. In Aarhus, the researchers contacted a
secretary by telephone when they had finished the
entry assessment of each patient. The secretary
then drew one lot from among five red and five
white lots out of a black box. When the block of
10 was used, the lots were redrawn. Block sizes
were unknown to the investigators.
InterventionsThe trial was pragmatic,
comparing integrated treatment defined by a set
of protocols with treatment as usual.
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Integrated treatmentThis was as assertive
community treatment enhanced by better specific
content via family involvement and social skills
training. Two multidisciplinary teams in
Copenhagen and one in Aarhus were established and
trained to provide integrated treatment.
Caseload reached a level of about 10. Each
patient was offered integrated treatment for a
period of two years. A primary team member was
designated for each patient and was then
responsible for maintaining contact and
coordinating treatment within the team and across
different treatment and support facilities.
Patients were visited in their homes or other
places in their community or at their primary
team member's office according to their
preference. During hospitalisation, treatment
responsibility was transferred to the hospital,
but a team member visited the patient once a
week. The office hours were Monday to Friday, 8
am to 5 pm. All team members had a mobile phone
with an answering function. Outside office hours,
patients could leave a message and be sure that
the team would respond the next morning. A crisis
plan was developed for each patient. If the
patient was reluctant about treatment, the team
stayed in contact with the patient and tried to
motivate the patient to continue treatment.
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Procesevalueringer er ikke effektevalueringer -
Og bliver det aldrig
Evaluering af kommunalt tilbud til
alkoholmisbrugere
Projektbeskrivelse Akuttilbuddet har til formål
at hjælpe misbrugere, som andre aktører ikke er i
stand til at hjælpe, fx fordi misbrugerne ikke er
motiverede til at indgå i et decideret
behandlingsforløb. Tilbuddet har siden 2003 været
benyttet af cirka 200 misbrugere, og det bemandes
af to socialfaglige medarbejdere, der står til
rådighed for personlig eller telefonisk kontakt
ved akut opståede problemer også uden for
almindelig kontortid. Projektmedarbejderne søger
at etablere en personlig relation til misbrugerne
og støtter dem fx i kontakten til behandlere,
læger og sagsbehandlere.
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Procesevalueringer er ikke effektevalueringer -
Og bliver det aldrig
RESULTATER Evalueringen af Horsens Kommunes
Akuttilbud viser, at projektet tjener som et
vigtigt supplement til den behandlingsindsats,
der i dag finder sted i amtsligt regi.
betydning af organisatorisk forankring osv.. Ved
denne type lokale projekter er der sjældent
ressourcer til at gennemføre egentlige
effektevalueringer. Ikke desto mindre kan der
hentes nyttig viden og skabes dokumentation for
et projekts indsats, hvis man evaluerer dets
proces, virkemåde og samarbejdsrelationer.
Evalueringen af Horsens Kommunes Akuttilbud er
baseret på kvalitative interviews med
projektmedarbejdere og samarbejdspartnere samt
analyser af skriftligt materiale
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Evidens-bevægelsen
27
Mindst 368 boghits på evidence-based medicine
på Amazon 17842 hits på Medline (artikler) på
søgeord evidence based medicine
Evidence-based medicine/practice
Evidence based health policy
Artikel-eksempel Meta-analysis chronic disease
self-management programs for older adults. Ann
Intern Med. 2005 Sep 20143(6)427-38.
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Hvad er evidence based medicine?

• The process of systematically finding,
  appraising, and using contemporaneous research
  findings as the basis for clinical decisions.
  Evidence-based medicine asks questions, finds and
  appraises the relevant data, and harnesses that
  information for everyday clinical practice.
• Evidence-based medicine follows four steps
• formulate a clear clinical question from a
  patient's problem
• search the literature for relevant clinical
  articles
• evaluate (critically appraise) the evidence for
  its validity and
• usefulness
• implement useful findings in clinical practice.
  
• The term "evidence based medicine" was coined at
  McMaster Medical School in Canada in the 1980's
  to label this clinical learning strategy, which
  people at the school had been developing for over
  a decade. (From BMJ 19953101122)

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Evidenshierarkiet på sundhedsområdet (følges i
Cochrane studier)
Evidenshierarkiet

• 1. Meta-analyser af randomiserede studier
• Randomiserede studier
• Kontrollerede studier med sammenligningsgruppe(r)
• Før-efter måling, uden sammenligningsgruppe
• Deskriptive analyser/kvalitative analyser m.m.
• Ekspert-vurdering og case-studier/kasuistik

Hovedvægten er på intern validitet (undgå bias),
ikke på ekstern validitet (generalisering)
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Cochrane studier/bibliotek
Welcome to The Cochrane Library 2005, Issue 3 the
best single source of reliable evidence about the
effects of healthcare The Cochrane Library is
designed to provide information and evidence to
support decisions taken in health care and to
inform those receiving care. The Cochrane Library
consists of a regularly updated collection of
evidence-based medicine databases. The databases
and the current numbers of records are
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Pretty much the Cochrane Hierarchy
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• RECOMMENDATIONS
• A combination of
• did it work (efficacy)?
• internal validitity
• will it work?
• among other things
• external validity

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