Det systematiske review - den systematiske oversigtsartikel. Andreas Lundh Det Nordiske Cochrane Center al@cochrane.dk

Transkript

1 Det systematiske review - den systematiske oversigtsartikel 1 Andreas Lundh Det Nordiske Cochrane Center al@cochrane.dk

2 Definition Systematisk oversigtsartikel = systematisk review

3 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.

4 Narrative vs. systematic Cook DJ et al. Ann Intern Med 1997.

5 Evidens hierarkiet

6 Hvad er en systematisk oversigtsartikel?

7 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?

8 Hvad er forskellen mellem en meta-analyse analyse og en systematiske oversigtsartikler?

9 Systematisk oversigtsartikel - kort Systematisk litteraturgennemgang der følger en præ-specificeret protokol

10 Systematisk oversigtsartikel - lang En oversigtsartikel med et klart tydeligt spørgsm rgsmål, der bruger systematiske og eksplicitte metoder til at identificere, udvælge lge, kritisk vurdere relevante undersøgelser og til at indsamle og analysere data fra inkludere studier. Statistiske metoder (meta-analyse) analyse) kan bruges til at analysere og opsummere resultaterne fra de inkludere studier. (Oversættelse fra Cochrane Handbook)

11 Meta-analyse analyse Statistisk metode til kvantitativ opsummering Kombinerer resultater fra flere uafhængige studier til ét t overordnet effektestimat

12 Systematisk oversigtsartikel Meta-analyse analyse systematisk oversigtsartikel meta-analyse

13 Systematiske oversigtsartikel - formål minimere bias øge statistisk styrke (meta-analyse) analyse) eksplorere forskelle i resultater mellem studier (bias, patientpopulation, behandlingsregime m.m.)

14 Systematiske oversigtsartikel - trin 1. Formulere klinisk spørgsm rgsmål 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

15 Klinisk spørgsm rgsmål Brug PICO metode (population, intervention, control, outcome) Eks. P I C O Pt er m. post-operative operative smerter Preop.. Gabapentin + standard smertebeh. Standard smertebeh. Smerter, analgetika forbrug, bivirk.

16 Identifikation af studier Formål: at identificere ALLE studier (undgå bias, øge styrke) påp ALLE sprog - Database søgning s (MEDLINE, EMBASE, CENTRAL etc.) - referencelister, håndsh ndsøgning af tidsskrifter, andre oversigtsartikler, kontakte eksperter, guidelines - identificere upublicerede studier (trial( registre, medicinal firmaer, forskere, abstracts fra konferencer etc.) (nb. minimere publikations bias)

17 Studie inklusion Objektive inklusions/eksklusionskriterier der kan reproduceres med samme resultater (sv.t( sv.t.. PICO i klinisk spørgsm rgsmål) 2 personer (en fra speciale og en uden for) inkluderer studier uafhængigt

18 Inklusionskriterier Seib et al. Can J Anesth 2006

19 Eksempel påp flow chart Stothard et al. JAMA 2009

20 Data ekstraktion Data fra studier (antal patienter, hændelser, h tid etc.) ekstraheres og indføres i standardiserede data-ark ark Udføres af 2 personer uafhængigt

21 Vurdere bias/intern validitet I For hvert studie vurderes risiko for bias - var randomiserings sekvensen tilfældig? ldig? - var allokeringen til grupper skjult? - var patienterne blindet? - var behandlere og plejepersonale blindet? - var effektmåls evaluatorer blindet? - var drop-out out og manglende data acceptabel? - var der ingen selektiv rapportering? - anden bias (eks. publikations bias)?

22 Vurdere bias/intern validitet II (Cochrane Handbook)

23 Analyse af studier Meta-analyse analyse hvis muligt, ellers deskriptiv analyse (nb. meta-analyse analyse kræver min. 2 studier!)

24 Forest plot Herkner el at. CDSR 2010

25 Sensitivitets analyse Herkner et al. CDSR 2010

26 Eksplorere heterogenecitet van Dalen et al. CDSR 2010

27 Konklusion På baggrund af resultater og undersøgelse af risiko for bias konkluderes i forhold til studiets kliniske spørgsm rgsmål

28 Publikationsbias? Li et al. CDSR 2009

29 Ingen mistanke om publikationsbias

30 Mistanke om publikationsbias

31 Meta-analyser 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

32 Anvendelse af systematiske oversigtsartikler Ved udarbejdelse af nationale guidelines og vurdering af sundhedsinterventioner Ved udarbejdelse af lokale instrukser Forud for iværks rksættelse af randomiserede kliniske forsøg Overblik over litteraturen om en given intervention

33 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 reviews kritisk! Clinical Evidence (BMJ): Mere brugervenligt, men koster penge (gratis påp RH)

34 metodik vs rapportering Rapport God Dårlig God Kan bruges Metodik Dårlig Kan ikke bruges Kan bruges? Kan ikke bruges Vi har brug for GODE studier, men ofte kan vi ikke skelne skidt fra kanel grundet dårlig rapportering

35 Hvad er en god systematisk oversigtsartikel? Metodik - hvad blev der gjort? (for læsere) l Assessment tools: Rapportering - hvad skal vi skrive vi gjorde? (for forfattere) Guidelines OQAQ Oxman AD et al. J Clin Epidemiol AMSTAR Shea BJ et al. J Clin Epidemiol QUOROM Moher et al. Lancet PRISMA Moher et al. PLoS Med 2009.

36 AMSTAR Assessment of Multiple SysTemAtic Reviews

37 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

38 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.

39 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

40 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

41 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

42 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 d beskrivelse af søgningsstrategi

43 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

44 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 s trial registre m.m.

45 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

46 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.

47 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

48 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

49 7. Was the scientific quality of the included studies assessed and documented? A A priori methods of assessment should be provided (e.g.,., for effectiveness studies if the author(s) chose to include only randomized,, double-blind, blind, placebo-controlled 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

50 7. Was the scientific quality of the included studies assessed and documented? A A priori methods of assessment should be provided (e.g.,., for effectiveness studies if the author(s) chose to include only randomized,, double-blind, blind, placebo-controlled 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

51 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

52 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 I results Ingen sammenkobling med resultaterne, ingen beskrivelse af score for de enkelte studier.

53 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,, I 2 ). 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

54 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,, I 2 ). 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?). ( No ) Population: hysterektomi, mastektomi, kolecystektomi m.m. Intervention: Forskellig dosis + anden analgetika Random effects er valgt, hvilket er rimeligt. Intet om ITT, Drop-outs outs,, Tabel 1+2 pool er data fra forskellige tidspunkter fra de samme studier Det er problematisk

55 10. Was the likelihood of publication bias assessed? An assessment of publication bias should include a combination of graphical aids (e.g( e.g.,., funnel plot, other available tests) and/or statistical tests (e.g( e.g.,., Egger regression test). Yes No Can't answer Not applicable

56 10. Was the likelihood of publication bias assessed? An assessment of publication bias should include a combination of graphical aids (e.g( e.g.,., funnel plot, other available tests) and/or statistical tests (e.g( e.g.,., Egger regression test). No Intet beskrevet i artiklen.

57 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

58 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

59 Samlet -AMSTAR 1. Was an a a priori design provided? Yes 2. Was there duplicate study selection and data extraction? Yes 3. Was a comprehensive literature search performed? Can t t tell 4. Was the status of publication (i.e., grey literature) Yes used as an inclusion criterion? 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 (Yes) studies assessed and documented? 8. Was the scientific quality of the included studies No used appropriately in formulating conclusions? 9. Were the methods used to combine (No) the findings of studies appropriate? 10. Was the likelihood of publication bias assessed? No 11. Were potential conflicts of interest included? No

60 Konklusion Hvad er resultatet? Kan vi stole påp resultatet? (bias) Hvad betyder resultatet for klinisk praksis? (generaliserbarhed)