Critical Appraisal of Journal Articles about Oral Ivermectin versus Malathion Lotion for Difficult-to-Treat Head Lice

Are the results valid?

Therap Yes,
A total of 812 patients from 376 households were randoml assi!ned to receive either ivermectin or malathion. "Abstract# $esult# pa!e %&'()

Was the assignment of patients to treatment randomized?

We ondu ted a multicenter# cluster-randomi*ed# double-blind# double-dumm # controlled trial omparing oral i!erme tin "at a dose of #$$ %g per &ilogram of 'od( weight) with $.*+ malathion lotion, ea h gi!en on da(s 1 and 8, for patients with li!e li e not eradi ated '( topi al inse ti ide used 2 to 6 wee&s 'efore enrollment. "Abstract# Methods# pa!e %&'()

Yes, Were all the patients who entered the trial a ounted for and attri'uted at its on lusion?
A total of 376 households, omprising 812 patients, were enrolled in the stud(. ,he i!erme tin group onsisted of 3-8 patients in 18* households. the malathion group onsisted of #1# patients in 1-1 households. /n da( 1* "the time at whi h the primar( end point was assessed), 3* of the 812 patients "#.3+) had 'een lost to follow0up, and *3 of the 812 patients "6.*+) did not omplete the stud(. "$esult# +tud ,articpants and Treatment# pa!e %&&()

Yes, Were patient1s lini ians and stud( personnel &ept 2'lind2 to treatment re ei!ed?
,o ensure that treatment remained 'linded, a dou'le0dumm( te hni3ue was used. All patients re ei!ed ta'lets, either i!erme tin or a !isuall( identi al pla e'o ta'let "of identi al omposition e4 ept for the i!erme tin, whi h was repla ed '( ellulose), and lotion, either $.*+ malathion or a pla e'o lotion ontaining 1$$+ isopropanol. "+tud Treatments and -lindin!# pa!e %&%()

Yes
,he in lusion riteria were an age of at least 2 (ears, weight of at least 1* &g, and head0li e infestation "defined as the presen e of li!e li e) onfirmed '( stud( staff '( om'ing the dr( hair with a dedi ated fine0toothed om', as pre!iousl( des ri'ed. 5i!e li e seen during this e4amination were ounted, to pro!ide 'aseline data. ,he other in lusion riterion was pre!iousl( failed treatment in either the inde4 patient or a household mem'er, defined as persisten e of head0li e infestation, despite topi al appli ation of a p(rethroid0 'ased or malathion inse ti ide 2 to 6 wee&s 'efore the da( 1 !isit, as reported '( the patient "or parent or guardian) at the da( 1 !isit. "+tud ,atients# pa!e %&%() Yes All patients re ei!ed ta'lets, either i!erme tin or a !isuall( identi al pla e'o ta'let "of identi al omposition e4 ept for the i!erme tin, whi h was repla ed '( ellulose), and lotion, either $.*+ malathion or a pla e'o lotion ontaining 1$$+ isopropanol. "+tud Treatments and -lindin!# pa!e %&%()

Were the groups similar at the start of the trial?

Were the groups treated e3uall( apart from the stud( inter!ention?

.hat are the results?

Therap
Anal(sis of the primar( end point in the intention to0treat population, a ording to the last0o'ser!ation0 arried0forward approa h, showed that on da( 1*, 378 of the 3-7 patients "-*.2+) in the i!erme tin group were free of head li e, as ompared with 3*2 of the #1# patients "8*.$+) in the malathion group 6ow large was the treatment effe t? "absolute difference# /0)1 percenta!e points. -*+ onfiden e inter!al :;<=, A'solute 7is& 7edu tion8 7elati!e 7is& #.6 to 1*.7. >?$.$$1). <n the per0proto ol population, the estimated absolute 7edu tion8 9um'er 9eeded to ,reat difference bet2een the t2o treatment !roups 2as 3)4 percenta!e points "-*+ ;<, 2.8 to 11.8. > @ $.$$2). At the lusters le!el, 171 of the 18* households "-2.#+) in the i!erme tin group were free of head li e, as ompared with 1*1 of the 1-1 households "7-.1+) in the malathion group "absolute difference# /4)5 percenta!e points . -*+ ;<, 6.# to 2$.#). "Outcomes# pa!e &0/() <n the intention0to0treat population, &6)17 of patients receivin! ivermectin 2ere lice-free on da /6# as compared 2ith %6)07 of those receivin! malathion "a'solute differen e, 1$.2 per entage points. &67 confidence 6ow pre ise was the estimate of interval 8CI9, #.6 to 1*.7. ,:0)00/). <n the per0proto ol population# &3)/7 of treatment effe t? ;onfiden e <nter!al patients in the ivermectin !roup 2ere lice-free on da /6# as compared 2ith %&)%7 of those in the malathion !roup "a'solute differen e, 7.3 per entage points. &67 CI, 2.8 to 11.8. , ; 0)001). "Abstract# $esult# pa!e %&'()

.ill the results help me in m patient care?

Therap Yes,
Anal(sis of the primar( end point in the intention to0treat population, a ording to the last0o'ser!ation0 arried0forward approa h, showed that on da( 1*, 378 of the 3-7 patients "-*.2+) in the i!erme tin group were free of head li e, as ompared with 3*2 of the #1# patients "8*.$+) in the malathion group "a'solute differen e, 1$.2 per entage points. -*+ onfiden e inter!al :;<=, #.6 to 1*.7. >?$.$$1). <n the per0proto ol population, the estimated a'solute differen e 'etween the two treatment groups was 7.3 per entage points "-*+ ;<, 2.8 to 11.8. > @ $.$$2). At the lusters le!el, 171 of the 18* households "-2.#+) in the i!erme tin group were free of head li e, as ompared with 1*1 of the 1-1 households "7-.1+) in the malathion group "a'solute differen e, 13.# per entage points. -*+ ;<, 6.# to 2$.#). /n da(s 2 and 8, i!erme tin was also superior to malathion, with a'solute differen es 'etween the two groups of 1$.1 per entage points and 2-.8 per entage points, respe ti!el(, and with effi a ( sustained through da(s 22 and 2- . /n da( 1*, 3- patients "8 in the i!erme tin group and 31 in the malathion group) had persistent infestation and therefore entered the e4tension phase, with a swit h to the other treatment. At da( 2-, 8 of the 8 patients "1$$+) re ei!ing malathion and 3$ of the 31 patients "-6.8+) re ei!ing i!erme tin no longer had head li e. 7egarding treatment preferen e, 78.3+ of the patients preferred ta'lets, 13.$+ preferred lotion, and 8.7+ had no preferen e. "Outcomes# pa!e &0/() ,wo serious lini al ad!erse e!ents were reported. A total of 7 of the 3-8 patients "1.8+) in the i!erme tin group and * of the #1# patients "1.2+) in the malathion group dis ontinued treatment 'e ause of an ad!erse e!ent. onl( three e!ents were Audged to 'e se!ere. ,he fre3uen ies of ad!erse e!ents were generall( similar among the age groups of 2 to * (ears, 6 to 12 (ears, and more than 12 (ears, 'ut in a'solute terms, the (oungest group had the fewest e!ents. "Adverse event# pa!e &0/-&01()

Were all lini all( rele!ant out omes onsidered?

Yes ;an the results 'e applied to m( patients?

Ivermectin ma be a !ood alternative to malathion 2hen topical insecticide resistance is suspected) ,he patients in luded in our large trial were re ruited from the ommunit( in four ountries, as a realisti sample of the general population, in whi h the degree of resistan e and the t(pe of resistan e "i.e., resistan e to a p(rethroid, malathion, or 'oth) ma( !ar( from one pla e to another. "Discussion# pa!e &04(

Are the 'enefits worth the harms and osts?

Yes
,he fre3uen ies of ad!erse e!ents were generall( similar among the age groups of 2 to * (ears, 6 to 12 (ears, and more than 12 (ears, 'ut in a'solute terms, the (oungest group had the fewest e!ents. "Adverse event# pa!e &0/-&01()

<n the general population, appro4imatel( #* million people in more than 3$ ountries ha!e re ei!ed 1*$ million doses of i!erme tin3* with no reported se!ere ad!erse e!ents, although the dose was lower than that used to eradi ate head li e in this stud(. "Discussion# pa!e &05()

Yogyakarta, 19 November 2011 Ko-Asisten, Preceptor,

Irmawati $'c

asy!"#a

#r$ Na%ia! &!"sniyati, 'p$ KK,