Methodology Checklist 2: Controlled Trials Trials SIGN Study identification identification (Include author, title, year of publication, publication, journal title, pages) pages )
Guideline topic:
Key Question No:
Reviewer: Reviewer:
Before completing Before completing this checklist consider: !" #s the the pa paper a randomised controlled trial or a controlled clinical trial$ trial$ #f in dou%t check t he study design algorithm availa%le availa%le from S#GN and make sure you have the correct checklist" #f it is a controlled clinical trial &uestions trial &uestions !"' !" and !" are not relevant and the study cannot %e rated higher than !* '" #s the paper paper relevant relevant to key &uestion$ +nalyse using using ,#-. (,atient or ,opulation #ntervention -omparison -omparison .utcome)" #/ N. R010-2 (give reason %elow)" #/ 30S complete the checklist" Reason for re4ection: !" ,aper not relevant to key &uestion
'" .ther reason (please specify):
SECTION 1: INTERNA INTERNAL L VALIDITY In a well conducted RCT study… !"!
Does this study do it?
2he study addresses an appropriate and clearly focused &uestion "i
3es
-an5t say !"'
2he assignment of su%4ects to treatment groups is randomised"ii
3es
+n ade&uate concealment concealment method method is used"iii
3es
!"7 !"9 !"9
!"
Su%4ec Su%4ects ts and and inve investi stiga gator tors s are are kept kept 6%l 6%lind ind55 a%ou a%outt trea treatme tment nt iv allocation"
3es
2he 2he only only dif diffe fere renc nce e %etw %etwee een n grou groups ps is is the the treat treatme ment nt und under er vi investigation"
!"=
+ll the su%4ec su%4ects ts are are analy analysed sed in the group groups s to which which they they were were randomly allocated (often referred to as intention to treat analysis)" ix
No
No
3es
No
-an5t say
3es
No
-an5t say
+ll releva relevant nt outcom outcomes es are measur measured ed in a stan standa dard rd valid valid and vii relia%le way"
No
-an5t say 8 3es
!";
!"!?
3es
-an5t say
2he treatm treatment ent and and contr control ol groups groups are simila similarr at the start start of of the the v trial"
No
-an5t say !"
-an5t say !"
No
No
-an5t say
>oes not apply
3es
-an5t say
No >oes not apply
/ile name : -hecklist ' A -ontrolled 2rials ,roduced %y: -arolyn Sleith
Bersion '"? ,age ! of
';C?7C'?!' Review date: None
SECTION : OVERALL ASSESS!ENT O" T#E ST$DY '"!
Dow well was the study done to minimise %ias$ Code as follows: xi
Digh &uality (**) +ccepta%le (*) Enaccepta%le A re4ect ?
'"'
2aking into account clinical considerations your evaluation of the methodology used and the statistical power of the study are you certain that the overall effect is due to the study intervention$
'"
+re the results of this study directly applica%le to the patient group targeted %y this guideline$
'"
Notes% Summarise the authors5 conclusions" +dd any comments on your own assessment of the study and the e@tent to which it answers your &uestion and mention any areas of uncertainty raised a%ove"
/ile name : -hecklist ' A -ontrolled 2rials ,roduced %y: -arolyn Sleith
Bersion '"? ,age ' of
';C?7C'?!' Review date: None
i
Enless a clear and well defined &uestion is specified it will %e difficult to assess how well the study has met its o%4ectives or how relevant it is to the &uestion you are trying to answer on the %asis of its conclusions" ii
Random allocation of patients to receive one or other of the treatments under investigation or to receive either treatment or place%o is fundamental to this type of study" iii
+llocation concealment refers to the process used to ensure that researchers are unaware which group patients are %eing allocated to at the time they enter the study" Research has shown that where allocation concealment is inade&uate investigators can overestimate the effect of interventions %y up to ?F" iv
linding refers to the process where%y people are kept unaware of which treatment an individual patient has %een receiving when they are assessing the outcome for that patient" #t can %e carried out up to three levels" Single %linding is where patients are unaware of which treatment they are receiving" #n dou%le %lind studies neither the clinician nor the patient knows which treatment is %eing given" #n very rare cases studies may %e triple %linded where neither patients clinicians nor those conducting the analysis are aware of which patients received which treatment" 2he higher the level of %linding the lower the risk of %ias in the study" v
,atients selected for inclusion in a trial must %e as similar as possi%le" 2he study should report any significant differences in the composition of the study groups in relation to gender mi@ age stage of disease (if appropriate) social %ackground ethnic origin or coHmor%id conditions" 2hese factors may %e covered %y inclusion and e@clusion criteria rather than %eing reported directly" /ailure to address this &uestion or the use of inappropriate groups should lead to the study %eing downgraded" vi
#f some patients received additional treatment even if of a minor nature or consisting of advice and counselling rather than a physical intervention this treatment is a potential confounding factor that may invalidate the results" If &ro'(s )ere not treated e*'all+, t-e st'd+ s-o'ld .e re/ected 'nless no ot-er e0idence is a0aila.le% #f the study is used as evidence it should %e treated with caution" vii
2he primary outcome measures used should %e clearly stated in the study" If t-e o'tcome meas'res are not stated, or t-e st'd+ .ases its main concl'sions on secondar+ o'tcomes, t-e st'd+ s-o'ld .e re/ected%
2he num%er of patients that drop out of a study should give concern if the num%er is very high" -onventionally a '?F drop out rate is regarded as accepta%le %ut this may vary" Some regard should %e paid to why patients dropped out as well as how many" #t should %e noted that the drop out rate may %e e@pected to %e higher in studies conducted over a long period of time" + higher drop out rate will normally lead to downgrading rather than re4ection of a study" i@
#n practice it is rarely the case that all patients allocated to the intervention group receive the intervention throughout the trial or that all those in the comparison group do not" ,atients may refuse treatment or contraHindications arise that lead them to %e switched to the other group" #f the compara%ility of groups through randomisation is to %e maintained however patient outcomes must %e analysed according to the group to which they were originally allocated irrespective of the treatment they actually received" (2his is known as intention to treat analysis") #f it is clear that analysis was not on an intention to treat %asis the study may %e re4ected" #f there is little other evidence availa%le the study may %e included %ut should %e evaluated as if it were a nonHrandomised cohort study" @
#n multiHsite studies confidence in the results should %e increased if it can %e shown that similar results were o%tained at the different participating centres" @i
Rate the overall methodological &uality of the study using the following as a guide: #i&- *'alit+ (**): Ia4ority of criteria met" Jittle or no risk of %ias" Results unlikely to %e changed %y further research" Acce(ta.le (*): Iost criteria met" Some flaws in the study with an associated risk of %ias -onclusions may change in the light of further studies" Lo) *'alit+ (?): 0ither most criteria not met or significant flaws relating to key aspects of study design" -onclusions likely to change in the light of further studies"
