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1 Plan today r r - dns Follow-up dsigns Ann-Mari Nybo Andrsn Dpartmnt of Public Halth øg PhD cours in Epidmioly dato Dias Enhdns 1 1. Nams, introductions 2. Prospctiv studis, principls 1. Cohort studis 2. RCTs 3. Th Danish National Birth Cohort 4. Studis xampls of diffrnt approachs and dsigns r Analytical study dsigns Epidmiolic study dsigns r udn ni strdn, dns Principls Strhts and waknsss Ral lif xampls Dias 3 Intrvntion Cohort Cas-control Corrlation studis Cross-sctional studis Cas-sris

2 Which dsign to us? SHOULD DEPEND ON THE PURPOSE! But also: Tim Ethics Mony Data CRITICAL APPROACH IS CRUCIAL Dias 6 Dsign of cohort studis Many nams.. COHORT STUDY follow-up study prospctiv study loitudinal study

3 Th cohort study Th modl An obsrvational dsign Primary idntification of th study bas Exposd and un-xposd individuals ar followd ovr Incidnc of outcom (halth, disas, bhaviour tc) in diffrnt xposur groups ar compard At last two points of masurmnt Population + O + O Typs of cohort studis Prospctiv vs. Historical cohort Prospctiv cohort Historical cohort Prospctiv cohort Historical cohort Ambi-dirctional cohort Nstd cas-control study in cohort rsachr rsachr

4 Othr cohort dsigns Tak car Ambi-dirctional cohort rsachr Nstd cas-control study in cohort rsachr?? Prospctiv Rtrospctiv Whn ar data collctd rtrospctivly? Always think about th in rlation to th outcom! DO NOT us th concpt rtrospctiv cohort Typs of cohort studis Prospctiv cohort Historical cohort Ambi-dirctional cohort Nstd cas-control study in cohort Cohort Typs of cohort studis Nstd cas-control study in cohort

5 Data sourcs in cohort studis Exposurs Qustionnairs Spcific inmation Potntials bias Rgistris non-spcific oftn no slction, chap minimal bias Famous cohorts Nurss Halth Study Framiham study British Physicians Study Outcoms Slf rports Issus about validity Rgistris ØstrbroGlostrup studis, HCPB EPIC studis (Kost-Kræft-Hlbrd) Danish National Birth Cohort (Bdr Sundhd Mor Barn).g. causs of dath Hospitalizd disass Journal fils Spcific inmations Clinical tst Points of obsrvation Dsign and intrprtations of cohort studis (1) Ar th xposd and th un-xposd group comparabl (othrwis)? How is th xposur dtrmind? objctivly, proxy, prsumd, slf rport Balancd collction of xposur? Epi læsni 6 Dias 19

6 Dsign and intrprtations of cohort studis (2) Dsign and intrprtations of cohort studis (3) How is th follow-up? Is attrition (non-rspons) corrlatd with xposur status? Is follow-up affctd by outcom? Is follow-up appropriat (latncy )? How is outcom dfind? Balancd collction of outcom inmation? Non-participation and rprsntativity : Not vry important intrnal validity, howvr, may b gnralisability (xtrnal validity) Pro t contra Frquncy masurs in cohort studis Advantags Tim rlation btwn xposur and outcom Mor outcom could b invstigatd (important public halth!) Rar xposurs Disadvantags Larg sampls sizs rar outcoms Tim consumi Loss of follow-up KIP = cumulatd incidnc proportion = nw vnts until th t numbr of prsons undr ri IR = incidnc rat = nw vnts cumulatd ri Population O O RR = IR IR = O Obs. O Obs.

7 Association masurs in cohort studis IR = nw vnts cumulatd ri Hazards = probability unit IRR and HR: (=rlativ ris) Ratios btwn xposd and un-xposd Population år øg Intrvntion studis (CLINICAL) TRIAL RCT: randomisd clinical trials An invstigation involvi intntional chanc in som aspcts of th status of th subjcts,.g. introduction of a prvntiv or thraputic rgimn, or dsignd to tst a hypothsizd rlationship JM Last: Dictionary of Epidmioly, Oxd 2001 r Rational intrvntion studis Exampls from prvntion. r udn ni strdn, dns Obsrvational studis ar suscptibl (nonrcnisd or non masurabl) confoundi.g. pts and allrgis in Swdn Evidnc-basd prvntion and tratmnt Un-documntd (and mayb harmful) tratmnts How about prvntion? øg Aspirin against prclampsia Calcium against prclampsia (Lanct 1994;343:619-29) (N El J Md 1997; 337: 69-76) Bta-Carotn and lu cancr (N El J Md 1994; 330: )

8 r Th Intrvntion Study 3 ky lmnts r udn ni strdn, dns Rsmbls th cohort study: invstigat th incidnc of outcom in groups of xposur HOWEVER Th rsarchr is in control of th study population and th xposur Th rsarchr crats an all othr qual situation by randomisation øg Randomisation: comparability of populations Placbo: comparability of tratmnt ffcts indpndnt of tratmnt circumstancs Blindi: comparability of inmation All ky lmnts ar not always fasibl! Randomisation Population Th Modl + O + O øg Dsign and intrprtation of intrvntion studis Is th population rprsntativ th population which th intrvntion is aimd Is th population larg nough to show an ffct: powr calculations basd on frquncis of outcom Follow-up considrations as with cohort studis

9 r r udn ni strdn, dns r r udn ni strdn, dns Som considrations in th analysis of RCTs Loss to follow-up crats important problms Is th outcom classification balancd? How is th complianc to th tratmnt? Intntion-to-trat analysis: Exampl Tuomilhto J, Lindström J, Eriksson JG t al. Prvntion of typ 2 diabts by chas in lifstyl amo subjcts with impaird glucos tolranc. N El J Md 2001;344: Exposur is an individualisd guidanc prram about wight rduction (5%), dit and physical activity. Th subjcts ar obs individuals, agd yars, and with impaird glucus tolranc (OGTT or fasti blood glucos) 6 yars of follow-up Outcom masur is a diagnosis of diabts Randomisd lifstyl Actual lif styl U: What could w think of? øg øg Diabts Intntion-to-trat analysis U = unobsrvd confoundi Advantag Th randomisation is kpt Problm: Misclassification of xposur (undrstimation of association masur) Randomisd Exposur Actual xposur U Outcom Rgrssion towards th man Statistical and biolical phnomnon E.g. tratmnt of patints with hyprtnsion E.g. Tratmnt of womn with multipl miscarriags May xplain som of th placbo ffcts Randomisation solvs th problm

10 r r udn ni strdn, dns Guidlins good practic in dsign and rporti af studis Obsrvational studis: STROBEstatmnt BMJ 2007; 335: RCTs: CONSORTstatmnt Ann Intrn Md 2001; 134: Mta analyss: QUORUMstatmnt Lanct 1999; 354: øg Rfrncs Links and rfrncs Nybo Andrsn A-M, Madsn M, Lawlor D. Birth cohorts: a rssourc lif cours studis. In: Family Mattrs. Oxd Univrsity Prss, 2009 Lawlor DA, Nybo Andrsn A-M, Batty D. Birth cohort studis: past, prsnt and futur. Int J Epidmiol 2009; Aug;38(4): Nybo Andrsn A-M, Oslr M. Kohortundrsøglsr bgyndr [Cohort studis bginnrs]. Ugrift Lægr 2004; 166: