Varför och hur gör vi systematiska kunskapssammanställningar

Bengt Järvholm

Göteborg 19 september 2012

Varför?

• Vill ha kunskap (= svar på fråga) • Vill ha upprepbarhet – hög transparens • Vill ha låg bias

• Fråga ”expert(er)” • Själv leta i litteraturen

– Primärstudier – Kunskapssammanställningar

• Systematiska • Icke-systematiska

Systematiska litteraturöversikter

Behandling

• Cochrane – RCT

– Observationsstudier

– ….

• Verkan resp biverkan

Kausalitet

• ”Hill”

• IARC

• Fysik/kemi/geografi/astronomi, historia,….

”Läkemedelsstudie”

• Experimentell del

– Kemi/cell/djurförsök

• Fas I studier

• Fas II studier

• Fas III studier

• Fas IV studier (postmarket studier)

Guidlines (vårdprogram)

• Systematiska litteraturgenomgångar • Kostnad • Etik • … • Handlingsprogram utifrån existerande kunskap och

värderingar Clinical Practice Guideline • Systematically developed statements to assist

practitioner and patient decisions about appropriate health care for specific clinical circumstances. NRC

• http://qualitymeasures.ahrq.gov/about/glossary.aspx

Cochrane

• Regelverk - ”upprepbar”

– Liknande resultat oavsett vem som gör studien

• Tolkning ingår

– Tolkare bör ha kunskap om området

– problematisering

Cochrane Reviews are systematic reviews of primary research in human health care and health policy, and are internationally recognised as the highest standard in evidence-based health care. They investigate the effects of interventions for prevention, treatment and rehabilitation. They also assess the accuracy of a diagnostic test for a given condition in a specific patient group and setting. They are published online in The Cochrane Library. Each systematic review addresses a clearly formulated question; for example: Can antibiotics help in alleviating the symptoms of a sore throat? All the existing primary research on a topic that meets certain criteria is searched for and collated, and then assessed using stringent guidelines, to establish whether or not there is conclusive evidence about a specific treatment. The reviews are updated regularly, ensuring that treatment decisions can be based on the most up-to-date and reliable evidence.

Cochrane.org (111110)

A Cochrane Review is a scientific investigation in itself, with a pre-planned methods section and an assembly of original studies (predominantly randomised controlled trials and clinical controlled trials, but also sometimes, non-randomised observational studies) as their ‘subjects’. The results of these multiple primary investigations are synthesized by using strategies that limit bias and random error. These strategies include a comprehensive search of all potentially relevant studies and the use of explicit, reproducible criteria in the selection of studies for review. Primary research designs and study characteristics are appraised, data synthesized, and results interpreted.

A systematic review is a review of a clearly formulated question that uses systematic and explicit methods to identify, select, and critically appraise relevant research, and to collect and analyse data from the studies that are included in the review. Statistical methods (meta-analysis) may or may not be used to analyse and summarise the results of the included studies. Meta-analysis refers to the use of statistical techniques in a systematic review to integrate the results of included studies.

PRISMA statement (www.prisma-statement.org http://www.bmj.com/content/339/bmj.b2535.full?view=long&pmid=19622551

Greenhalgh, BMJ, 1997;315:672 http://www.bmj.com/content/315/7109/672

• Explicit methods limit bias in identifying and rejecting studies • Conclusions are more reliable and accurate because of methods used • Large amounts of information can be assimilated quickly by healthcare

providers, researchers, and policymakers • Delay between research discoveries and implementation of effective

diagnostic and therapeutic strategies may be reduced • Results of different studies can be formally compared to establish

generalisability of findings and consistency (lack of heterogeneity) of results • Reasons for heterogeneity (inconsistency in results across studies) can be

identified and new hypotheses generated about particular subgroups • Quantitative systematic reviews (meta-analyses) increase the precision of the

overall result

Fördelar med systematiska översikter

Greenhalgh, BMJ, 1997;315:672 http://www.bmj.com/content/315/7109/672

How to read a paper: Papers that summarise other papers (systematic

reviews and meta-analyses)

Greenhalgh, BMJ, 1997;315:672 http://www.bmj.com/content/315/7109/672

The clinical question • “Do anticoagulants prevent strokes in patients with atrial fibrillation?”

should be refined as an objective: • “To assess the effectiveness and safety of warfarin-type anticoagulant

therapy in secondary prevention (that is, following a previous stroke or transient ischaemic attack) in patients with non-rheumatic atrial fibrillation: comparison with placebo.”

Frågan måste vara preciserad

Greenhalgh, BMJ, 1997;315:672 http://www.bmj.com/content/315/7109/672

• Methodological quality—the extent to which the design and conduct are likely to have prevented systematic errors (bias)

• Precision—a measure of the likelihood of random errors (usually depicted as the width of the confidence interval around the result)

• External validity—the extent to which the results are generalisable or applicable to a particular target population

Värdering av primärstudier

Ranking av studier (intervention)

• RCT

• Kohort/case referent

• Övriga

– Tvärsnittsstudier

– Fallrapporter

Värdering av studier

• Kräver specialkompetens inom fältet

– Bedöma kvalitet

– Särskilt svårt att bedöma ”intervention”/exponering vid ”icke-läkemedel”

• Lätt att medvetet göra en ”negativ studie” utan att fuska

• Svårt att göra en ”positiv studie” utan att fuska

• Dålig genomgång – man vet ingenting

Begränsningar

• Kontextberoende

– Return to work (RTW)

• Lagstiftning, tidpunkt, patientgrupp, ekonomisk konjunktur ….

– Studien genomförd på medelålders män

• Gäller resultaten för äldre multisjuka kvinnor

• Vi vet ingenting om någonting

– Slutsats för den ”okunnige”/kritiske

Randomisering

• Undviker selektion bias

• Påverkar inte kontrast mellan intervention/kontroll

– [jfr exponerad/oexponerad]

• Dieselavgaser

Järvholm & Reuterwall OEM 2012

Arbete o Hälsa 2012:46

Metaanalys

Systematiska översikter över systematiska översikter

Kvalitet systematiska översikter

• Sign • R-amstar (11 criteria, graded 1-4)

– (1) A priori design • Clear and focused question • Description of inclusion criteria • Study protocol published/registered in advance

– Duplicate review (2 persons reading everything) – … – (7) was the quality of included studies assessed and

documented – … – (11) conflict of interest

R- amstar: 7. Was the scientific quality of the included studies

assessed and documented?

• A priori methods are provided

• The scientific quality of the included studies appears to be meaningful

• Discussion/recognition/awareness of level of evidence is present

• Quality of evidence is rated/ranked based on characterized instruments

Systematiska översikter två synsätt

Vetenskapligt

• Kompetens om frågeställningen central

• Diskuterande

• Internationell publicering

Administrativt

• Kompetens om proceduren central

• Publicering i egen regi, nationellt språk

• policynära

Källor för systematiska kunskapssammanställningar

• Cochrane • Cambell • Tidskrifter med goda refereesystem

• Perosh

• Lägre kvalitet a priori

– A o H – SBU – …

Kausalitet

• Filosofiskt problem

– Astronomi

– Fysik

– Statsvetenskap

– Ekonomi

– Medicin

• ”Hill” (kritik av p-värdet)

• IARC (mekanistiska studier + epidemiologiska studier + värdering/röstning)

Kausalitet

Olika kriterier om

– Prevention

– Arbetsskada

– Skadestånd

– Straffa

Ex. MS – exponering för organiska lösningsmedel

http://www.lu.se/o.o.i.s?id=12588&postid=1715782

Användbara länkar (utöver de som finns i texten)

• Cochranes bibliotek över översikter http://www.cochrane.org/cochrane-reviews

• Cambell collaboration (fr a sammanställningar inom socialvetenskaper): http://www.campbellcollaboration.org/library.php

• PEROSH (sammanslutning av arbetsmiljöinstitut i Europa, länken är till deras sammanställningar av systemiska kunskapssammanställningar): http://www.perosh.eu/p/clearinghouse

• Amstar – kvalitetssystem: Open Dent J. 2010 Jul 16;4:84-91. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948145/

• SIGN – kvalitetskriterier: http://www.sign.ac.uk/methodology/checklists.html

• SBU: SBU.se • Sammanställningar inom Arbete och Hälsa:

https://gupea.ub.gu.se/simple-search?query=arbete+och+h%C3%A4lsa&submit=S%C3%B6k (leder till hemsidan där man sedan kan söka vidare)