Protokol artikler hvorfor, form og hvornår

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1 Protokol artikler hvorfor, form og hvornår Erik Poulsen Institute of Sports Science and Clinical Biomechanics Nordic Institute of Chiropractic and Clinical Biomechanics Department of Orthopaedic Surgery and Traumatology, Odense University Hospital

2 Hvad er en protokol artikel?

3 Alle forskningsprojekter har en protokol Forskningsmidler, VEK, Datatilsynet, arbejdsplan Klar beskrivelse af: Baggrund / rationale Hypotese / formål Metode Statistik Hvem gør hvad Tidshorisont F Godlee. BMC News and Views 2001

4 Hvorfor? Prevention of poor medical research Protokol tilsendt fondsgiver vs. indsendt artikel ændring i styrkeberegning How prevent poor medical research? By publication of protocols for proposed or ongoing research particular for RCTs 2001: 2 protocols published DG Altman. BMJ 1994; I Chalmers & DG Altman, Lancet 1999; F Godlee. BMC News and Views 2001

5 Primary outcomes Comparison of registered and published primary outcomes in RCTs 147/323 adequately registered in 2008 Registration lacking 89/323 45/323 registered after completion 39/323 no clear description of primary outcome 46/147 discrepancies between registered and published S Mathieu et al. JAMA 2009;302:977-84

6 Sample size Comparison between publications and protocols Discrepancies in sample size calculation and analyses reported 70 reported studies from Copenhagen and Frederiksberg 11/62 reported the same sample size calculation AW Chan et al. BMJ 2008;337:a2299

7 Arthroplasty Comparison of arthroplasty trial publications after registration in ClinicalTrials.gov 23% af registrerede RCTs bliver publiceret (23/101) 91/101 omhandler knæ og/eller hofte Ofte ændring af måden data præsenteres på i forhold til beskrivelsen ved registrering Smith et al. J Arthroplasty 2012;27:1283-8

8 Patient education o Inadequate description of educational interventions in ongoing RCTs Pino et al (Epub ahead of print)

9 Patient education o Inadequate description of educational interventions in ongoing RCTs Rheumatology o Misleading abstract conclusions in RCTs in rheumatology 25% have misleading conclusions Especially those with negative results Mathieu et al Joint Bone Spine;79:262-67

10 Physical therapy interventions Many Randomized Trials of Physical Therapy Interventions Are Not Adequately Registered: A Survey of 200 Published Trials 2009, 67/200 registered 5/200 adequate registration Primary outcome and time point of measurement RZ Pinto et al. Phys Ther 2012, Nov 2 (Epub ahead of print)

11 Noninferiority and Equivalence RCTs Important deficiencies regarding: noninferiority margins results not adequately reported conclusions at times misleading Le Henanff et al. JAMA 2006;295:

12 Formål - opsamling Sammenligning med oprindelig plan og publicerede resultater Undgå data dredging Minimér post-hoc ændring af hypoteser design, styrkeberegning og analyseplaner

13 Formål - opsamling Sammenligning med oprindelig plan og publicerede resultater Undgå data dredging fisketur Minimér post-hoc ændring af hypoteser design, styrkeberegning og analyseplaner

14 Formål Interessenter kan følge med i hvilke RCTs er sat i gang Minimér publikations bias En etisk diskussion da kan medføre forkerte behandling baseret på falske resultater

15 CONSORT Systematic reviews on effect of CONSORT Turner et al. Nov 2012, Cochrane Database Syst Rev. Reporting of RCTs remains suboptimal but is improving

16 CONSORT CONsolidated Standards Of Reporting Trials 1996 JAMA, Begg et al. parallel group RCTs 2001 JAMA, Moher et al. revision 2004 BMJ, Campbell et al. cluster RCTs 2007, Int J Surgery, Carney surgery 2007, Homeopathy, Dean et al. - homeopathy 2008, BMJ, Zwarenstein et al. pragmatic trials 2008, Nurs Outlook, Smith et al. nursing literature 2008 Ann Intern Med, Boutron et al. RCTs of non-pharmacologic treatment 2010 JAMA, Reporting of RCTS with statistical nonsignificant results 2010 BMJ most recent update, Schulz et al. Flow-chart and checklists

17 118 randomized 39 (patient education) 43 (patient education plus manual therapy) 36 (minimal control intervention) Allocated 2 bilateral hip pain 5 excl.: 1 bilateral hip pain, 2 polyarthritis, 1 no hip OA, 1 neuropathy Baseline 1 withdrew: no commitment 4 withdrew: 1 wanted operation, 1 no commitment, 1 operated for other reasons, 1 deteriorated after MT 4 withdrew: 3 unhappy with group, 1 wanted operation Primary end-point weeks 1 had hip surgery months 11 had hip surgery 3 had hip surgery 6 had hip surgery months

18 Checklists

19 Registrering Med unik identifikationsnummer undgå overrapportering Reducér underrapportering ISRCTN International Standard Randomized Controlled Trial Number, controlled-trials.com NCT US-NIH - clinicaltrials.gov EU clinical trial register clinicaltrialregister.eu ANZCTR Australien og New Zeeland

20 Form af protokol artiklen

21 Baggrund Design Hypotese(r) + formål Metode Protokol form Single center / multicenter Primær og sekundære effektmål Reproducerbarhed, validering og responsiveness Bivirkninger Statistisk plan Oftest ingen word limits da tidsskrifter kun er online

22 Protokol form Tidskrifter for protokoller BMC Muskuloskel Dis BMC Public Health BMC Fam Pract BMJ Open Trials Brug ovenstående som idé grundlag Søg PubMed: study protocol + emneord

23 Hvornår?

24 Hvornår? Registrering i RCT databaser Før inklusion af patienter Indsendelse af protokol til tidsskrift Så tidligt som muligt

25 Husk! Afvigelser fra protokollen er OK Men de skal nævnes i artiklen med begrundelse

26 Informationskilder D Moher et al J Clin Epidemiol; 63:e1-37 o CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomized trials KF Schulz et al BMJ; 340:c332 CONSORT Statement: updated guidelines for reporting parallel group RCTs

27 Guidelines for reporting EQUATOR network

28 Tak for opmærksomheden