1. No category

Det systematiske review
- den systematiske
oversigtsartikel
1
Andreas Lundh
Det Nordiske
Cochrane Center
al@cochrane.dk
Definition
Systematisk oversigtsartikel = systematisk review
Hvorfor oversigtsartikler?
Alene MEDLINE har over
19 millioner artikler i over
5000 tidsskrifter
En læge skal læse 17
artikler/dag for at være
fagligt opdateret
Haynes RB et al. ACP Journal Club 1992.
Narrative vs. systematic
Cook DJ et al. Ann Intern Med 1997.
Evidens hierarkiet
Hvad er en systematisk
oversigtsartikel?
Hvad er en systematisk
oversigtsartikel?
garbage in – garbage out?
a mixing of apples and oranges?
piling of manure and hoping it will smell like roses?
Hvad er forskellen mellem en meta-analyse
og en systematiske oversigtsartikler?
Systematisk oversigtsartikel - kort
Systematisk litteraturgennemgang der
følger en præ-specificeret protokol
Systematisk oversigtsartikel - lang
En oversigtsartikel med et klart tydeligt spørgsmål,
der bruger systematiske og eksplicitte metoder til
at identificere, udvælge, kritisk vurdere
relevante undersøgelser og til at indsamle og
analysere data fra inkludere studier. Statistiske
metoder (meta-analyse) kan bruges til at analysere
og opsummere resultaterne fra de inkludere
studier.
(Oversættelse fra Cochrane Handbook)
Meta-analyse
Statistisk metode til kvantitativ opsummering
Kombinerer resultater fra flere uafhængige
studier til ét overordnet effektestimat
Systematisk oversigtsartikel
Meta-analyse
systematisk oversigtsartikel
meta-analyse
Systematiske oversigtsartikel formål
minimere bias
øge statistisk styrke (meta-analyse)
eksplorere forskelle i resultater mellem studier
(bias, patientpopulation, behandlingsregime
m.m.)
Systematiske oversigtsartikel - trin
1. Formulere klinisk spørgsmål
2. Identificere studier
3. Inkludere/ekskludere studier
4. Data ekstraktion fra studier
5. Kritisk vurdere bias/intern validitet i studier
6. Analyse af studier
7. Konklusion
Klinisk spørgsmål
Brug PICO metode (population, intervention,
control, outcome)
Eks.
P
I
C
O
Pt’er m. post-operative smerter
Preop. Gabapentin + standard smertebeh.
Standard smertebeh.
Smerter, analgetika forbrug, bivirk.
Identifikation af studier
Formål: at identificere ALLE studier (undgå bias,
øge styrke) på ALLE sprog
- Database søgning (MEDLINE, EMBASE,
CENTRAL etc.)
- referencelister, håndsøgning af tidsskrifter, andre
oversigtsartikler, kontakte eksperter, guidelines
- identificere upublicerede studier (trial registre,
medicinal firmaer, forskere, abstracts fra konferencer
etc.) (nb. minimere publikations bias)
Studie inklusion
Objektive inklusions/eksklusionskriterier der kan
reproduceres med samme resultater (sv.t. PICO i
klinisk spørgsmål)
2 personer (en fra speciale og en uden for)
inkluderer studier uafhængigt
Inklusionskriterier
Seib et al. Can J Anesth 2006
Eksempel på flow chart
Stothard et al. JAMA 2009
Data ekstraktion
Data fra studier (antal patienter, hændelser,
tid etc.) ekstraheres og indføres i standardiserede
data-ark
Udføres af 2 personer uafhængigt
Vurdere bias/intern validitet I
For hvert studie vurderes risiko for bias
- var randomiserings sekvensen tilfældig?
- var allokeringen til grupper skjult?
- var patienterne blindet?
- var behandlere og plejepersonale blindet?
- var effektmåls evaluatorer blindet?
- var drop-out og manglende data acceptabel?
- var der ingen selektiv rapportering?
- anden bias (eks. publikations bias)?
Vurdere bias/intern validitet II
(Cochrane Handbook)
Analyse af studier
Meta-analyse hvis muligt, ellers deskriptiv analyse
(nb. meta-analyse kræver min. 2 studier!)
Forest plot
Herkner el at. CDSR 2010
Sensitivitets analyse
Herkner et al. CDSR 2010
Eksplorere heterogenecitet
van Dalen et al. CDSR 2010
Konklusion
På baggrund af resultater og undersøgelse
af risiko for bias konkluderes i forhold til
studiets kliniske spørgsmål
Publikationsbias?
Li et al. CDSR 2009
Ingen mistanke om publikationsbias
Mistanke om publikationsbias
Meta-analyser
Faldgruber & muligheder
Ensartet effekt mellem de
enkelte studier - forskelle
kan forklares med
statistisk variation
Publikationsbias kan
skævvride resultatet
Tvivlsom metodologisk
kvalitet af studier kan
give et vildledende
resultat
Grafisk og statistisk
påviselig heterogenicitet
kan generere forklarende
hypoteser
- og rejse mistanke om
publikations- og andre
typer bias
Anvendelse af systematiske
oversigtsartikler
Ved udarbejdelse af nationale guidelines og
vurdering af sundhedsinterventioner
Ved udarbejdelse af lokale instrukser
Forud for iværksættelse af randomiserede
kliniske forsøg
Overblik over litteraturen om en given
intervention
Anvendelse i klinisk praksis
Vanskelig: Kræver tid
Resultaterne er ikke altid præsenteret
brugervenligt eller hurtigt tilgængeligt
Ikke alle reviews holder samme standard, og det
er vigtigt at vurdere Cochrane-reviews kritisk!
Clinical Evidence (BMJ): Mere brugervenligt,
men koster penge (gratis på RH)
metodik vs rapportering
Rapport
God
Metodik
God
Dårlig
Kan bruges Kan ikke bruges
Dårlig Kan bruges? Kan ikke bruges
Vi har brug for GODE studier, men ofte kan vi
ikke skelne skidt fra kanel grundet dårlig
rapportering
Hvad er en god systematisk
oversigtsartikel?
Metodik
Rapportering
- hvad blev der gjort?
(for læsere)
- hvad skal vi skrive vi gjorde?
(for forfattere)
Assessment tools:
Guidelines
OQAQ
QUOROM
Oxman AD et al. J Clin Epidemiol 1991.
Moher et al. Lancet 1999.
AMSTAR
PRISMA
Shea BJ et al. J Clin Epidemiol 2009.
Moher et al. PLoS Med 2009.
AMSTAR
Assessment of Multiple SysTemAtic Reviews
1. Was an 'a priori' design provided?
The research question and inclusion criteria should be
established before the conduct of the review.
□ Yes
□ No
□ Can't answer
□ Not applicable
1. Was an 'a priori' design provided?
The research question and inclusion criteria should be
established before the conduct of the review.
⌧ Yes
Ingen beskrivelse af protokol, men under study selection
formentligt sandt.
2. Was there duplicate study
selection and data extraction?
There should be at least two independent data extractors
and a consensus procedure for disagreements should be in
place.
□ Yes
□ No
□ Can't answer
□ Not applicable
2. Was there duplicate study
selection and data extraction?
There should be at least two independent data extractors
and a consensus procedure for disagreements should be in
place.
⌧ Yes
Under study selection
Under data extraction
3. Was a comprehensive
literature search performed?
At least two electronic sources should be searched. The report must
include years and databases used (e.g., Central, EMBASE, and
MEDLINE). Key words and/or MESH terms must be stated, and where
feasible, the search strategy should be provided. All searches
should be supplemented by consulting current contents, reviews,
textbooks, specialized registers, or experts in the particular field of
study, and by reviewing the references in the studies found.
□ Yes
□ No
□ Can't answer
□ Not applicable
3. Was a comprehensive
literature search performed?
At least two electronic sources should be searched. The report must
include years and databases used (e.g., Central, EMBASE, and
MEDLINE). Key words and/or MESH terms must be stated, and where
feasible, the search strategy should be provided. All searches
should be supplemented by consulting current contents, reviews,
textbooks, specialized registers, or experts in the particular field of
study, and by reviewing the references in the studies found.
⌧ Can't answer
Muligvis, dårlig
beskrivelse af
søgningsstrategi
4. Was the status of publication (i.e., grey
literature) used as an inclusion criterion?
The authors should state that they searched for reports
regardless of their publication type. The authors should
state whether or not they excluded any reports (from the
Systematic review), based on their publication status,
language etc.
□ Yes
□ No
□ Can't answer
□ Not applicable
4. Was the status of publication (i.e., grey
literature) used as an inclusion criterion?
The authors should state that they searched for reports
regardless of their publication type. The authors should
state whether or not they excluded any reports (from the
Systematic review), based on their publication status,
language etc.
⌧ Yes
Under study identification
Dog ikke søgt trial registre m.m.
5. Was a list of studies
(included and excluded) provided?
A list of included and excluded studies should be provided.
□ Yes
□ No
□ Can't answer
□ Not applicable
5. Was a list of studies
(included and excluded) provided?
A list of included and excluded studies should be provided.
⌧ No
Kun inkluderede studier i tabel, ingen flow chart el. lign.
beskrivelse af ekskluderede studier.
6. Were the characteristics of the
included studies provided?
In an aggregated form, such as a table, data from the
original studies should be provided on the participants,
interventions, and outcomes. The ranges of characteristics
in all the studies analyzed, e.g., age, race, sex, relevant
socioeconomic data, disease status, duration, severity, or
other diseases should be reported.
□ Yes
□ No
□ Can't answer
□ Not applicable
6. Were the characteristics of the
included studies provided?
In an aggregated form, such as a table, data from the
original studies should be provided on the participants,
interventions, and outcomes. The ranges of characteristics
in all the studies analyzed, e.g., age, race, sex, relevant
socioeconomic data, disease status, duration, severity, or
other diseases should be reported.
(⌧ Yes)
Kan diskuteres da
mange karakteristika
er udeladt
7. Was the scientific quality of the included
studies assessed and documented?
‘‘A priori’’ methods of assessment should be provided (e.g.,
for effectiveness studies if the author(s) chose to include
only randomized, double-blind, placebo-controlled studies,
or allocation concealment as inclusion criteria); for other
types of studies, alternative items will be relevant.
□ Yes
□ No
□ Can't answer
□ Not applicable
7. Was the scientific quality of the included
studies assessed and documented?
‘‘A priori’’ methods of assessment should be provided (e.g.,
for effectiveness studies if the author(s) chose to include
only randomized, double-blind, placebo-controlled studies,
or allocation concealment as inclusion criteria); for other
types of studies, alternative items will be relevant.
(⌧ Yes)
Kan diskuteres, idet
Jadad scale er problematisk
8. Was the scientific quality of the
included studies used appropriately in
formulating conclusions?
The results of the methodological rigor and scientific quality
should be considered in the analysis and the conclusions of
the review, and explicitly stated in formulating
recommendations.
□ Yes
□ No
□ Can't answer
□ Not applicable
8. Was the scientific quality of the
included studies used appropriately in
formulating conclusions?
The results of the methodological rigor and scientific quality
should be considered in the analysis and the conclusions of
the review, and explicitly stated in formulating
recommendations.
⌧ No
Ingen sammenkobling
med resultaterne, ingen
beskrivelse af score for
de enkelte studier.
I results
9. Were the methods used to combine the
findings of studies appropriate?
For the pooled results, a test should be done to ensure the studies
were combinable, to assess their homogeneity (i.e., Chi-squared test
for homogeneity, I2). If heterogeneity exists,a random effects model
should be used and/or the clinical appropriateness of combining should
be taken into consideration (i.e., is it sensible to combine?).
□ Yes
□ No
□ Can't answer
□ Not applicable
9. Were the methods used to combine the
findings of studies appropriate?
For the pooled results, a test should be done to ensure the studies
were combinable, to assess their homogeneity (i.e., Chi-squared test
for homogeneity, I2). If heterogeneity exists,a random effects model
should be used and/or the clinical appropriateness of combining should
be taken into consideration (i.e., is it sensible to combine?).
Population: hysterektomi, mastektomi, kolecystektomi m.m.
(⌧ No ) Intervention: Forskellig dosis + anden analgetika
Random effects er valgt, hvilket er rimeligt.
Intet om ITT, Drop-outs, Tabel 1+2 pool’er data fra forskellige
tidspunkter fra de samme studier
Det er problematisk
10. Was the likelihood of publication
bias assessed?
An assessment of publication bias should include a
combination of graphical aids (e.g., funnel plot, other
available tests) and/or statistical tests (e.g., Egger
regression test).
□ Yes
□ No
□ Can't answer
□ Not applicable
10. Was the likelihood of publication
bias assessed?
An assessment of publication bias should include a
combination of graphical aids (e.g., funnel plot, other
available tests) and/or statistical tests (e.g., Egger
regression test).
⌧ No
Intet beskrevet i artiklen.
11. Was the conflict of interest included?
Potential sources of support should be clearly
acknowledged in both the systematic review and the
included studies.
□ Yes
□ No
□ Can't answer
□ Not applicable
11. Was the conflict of interest included?
Potential sources of support should be clearly
acknowledged in both the systematic review and the
included studies.
⌧ No
Intet i artiklen om hverken studierne el. den systematiske
oversigtsartikel
Samlet -AMSTAR
1. Was an ‘‘a priori’’ design provided?
Yes
2. Was there duplicate study selection and data extraction?
Yes
3. Was a comprehensive literature search performed?
Can’t tell
4. Was the status of publication (i.e., grey literature)
used as an inclusion criterion?
Yes
5. Was a list of studies (included and excluded) provided?
No
6. Were the characteristics of the included studies provided?
(Yes)
7. Was the scientific quality of the included
studies assessed and documented?
(Yes)
8. Was the scientific quality of the included studies
used appropriately in formulating conclusions?
No
9. Were the methods used to combine
the findings of studies appropriate?
(No)
10. Was the likelihood of publication bias assessed?
No
11. Were potential conflicts of interest included?
No
Konklusion
Hvad er resultatet?
Kan vi stole på resultatet?
(bias)
Hvad betyder resultatet for klinisk praksis?
(generaliserbarhed)