RESEARCH ARTICLE
Randomized clinical ials in o hodon ics a e
a ely egis e ed a p io i and o en published
la e o no a all
Spy idon N. Papageo giou
1
*, Geo gios N. An onoglou
2,3
, Geo ge K. Sa
´ndo
2,4
,
Theodo e Eliades
1
1Clinic o O hodon ics and Pedia ic Den is y, Cen e o Den al Medicine, Uni e si y o Zu ich, Zu ich,
Swi ze land, 2Ins i u e o Den is y, Depa men o O al and Maxillo acial Su ge y, Uni e si y o Oulu, Oulu,
Finland, 3Depa men o Pe iodon ology and Implan Biology, Den al School, A is o le Uni e si y o
Thessaloniki, Thessaloniki, G eece, 4BioMediTech, Ins i u e o Bioscience and Technology, Uni e si y o
Tampe e, Tampe e, Finland
*[email p o ec ed]
Abs ac
A p io i egis a ion o andomized clinical ials is c ucial o he anspa ency and c edibili y
o hei indings. Aim o his s udy was o assess he equency wi h which egis e ed and
comple ed andomized ials in o hodon ics a e published. We sea ched ClinicalT ials.go
and ISRCTN o egis e ed andomized clinical ials in o hodon ics ha had been com-
ple ed up o Janua y 2017 and judged he publica ion s a us and da e o egis e ed ials
using a sys ema ic p o ocol. S a is ical analysis included desc ip i e s a is ics, chi-squa e o
Fishe exac es s, and Kaplan-Meie su i al es ima es. F om he 266 o hodon ic ials eg-
is e ed up o Janua y 2017, 80 ials had been comple ed and included in he p esen s udy.
Among hese 80 included ials, he majo i y (76%) we e egis e ed e ospec i ely, while
only 33 (41%) we e published a he ime. The median ime om comple ion o publica ion
was 20.1 mon hs (in e qua ile ange: 9.1 o 31.6 mon hs), while su i al analysis indica ed
ha less han 10% o he ials we e published a e 5 yea s om hei comple ion. Finally,
22 (28%) o comple ed ials emain unpublished e en a e 5 yea s om hei comple ion.
Publica ion a es o egis e ed andomized ials in o hodon ics emained low, e en 5 yea s
a e hei comple ion da e.
In oduc ion
Randomized clinical ials a e he gold s anda d in compa a i e e ec i eness esea ch, due o
hei explici me hods, in e nal alidi y, and anspa ency. C ucial o his anspa ency is he
p o ision o an a p io i designed p o ocol ha delinea es each ial aspec . This can also be
used o compa e he o iginal ial plan wi h i s subsequen publica ion [1] o asce ain he i-
al’s o iginal scope, as well as minimize he isk o da a d edging. Fu he mo e, a p io i egis a-
ion o clinical ials can sa egua d agains dange s like delayed publica ion o non-publica ion
o ials, selec i e epo ing o ou comes, pe p o ocol a he han in en ion- o- ea analyses,
PLOS ONE | h ps://doi.o g/10.1371/jou nal.pone.0182785 Augus 4, 2017 1 / 13
a1111111111
a1111111111
a1111111111
a1111111111
a1111111111
OPEN ACCESS
Ci a ion: Papageo giou SN, An onoglou GN,
Sa
´ndo GK, Eliades T (2017) Randomized clinical
ials in o hodon ics a e a ely egis e ed a p io i
and o en published la e o no a all. PLoS ONE 12
(8): e0182785. h ps://doi.o g/10.1371/jou nal.
pone.0182785
Edi o : Pe e M. Milg om, Uni e si y o
Washing on, UNITED STATES
Recei ed: May 16, 2017
Accep ed: July 24, 2017
Published: Augus 4, 2017
Copy igh : ©2017 Papageo giou e al. This is an
open access a icle dis ibu ed unde he e ms o
he C ea i e Commons A ibu ion License, which
pe mi s un es ic ed use, dis ibu ion, and
ep oduc ion in any medium, p o ided he o iginal
au ho and sou ce a e c edi ed.
Da a A ailabili y S a emen : All ele an da a a e
wi hin he pape and i s Suppo ing In o ma ion
iles.
Funding: No unding o disclose o his s udy.
Compe ing in e es s: The au ho s ha e decla ed
ha no compe ing in e es s exis .
and ial o e laps among pape s included wi hin sys ema ic e iews [1–4]. Such a p io i egis-
e ed ial p o ocols can be ei he published as s andalone publica ions [5] and/o be egis e ed
in eely accessible online eposi o ies [6].
One such eely accessible online eposi o y is ClinicalT ials.go (h ps://clinical ials.go /),
a ial egis y and esul s da abase main ained by he US Na ional Lib a y o Medicine.
Al hough he e is no o mal equi emen ha all unded ials mus be egis e ed in Clinical-
T ials.go , he In e na ional Commi ee o Medical Jou nal Edi o s (ICMJE) began om 2005
equi ing ial egis a ion as a p e equisi e o publica ion in any o i s membe jou nals [7].
This led o a conside able inc ease o ials being egis e ed, which now each se e al hund eds
o new ials being egis e ed each week [8]. Ano he well-known egis y o clinical ials in
medicine is he In e na ional S anda d Randomised Con olled T ial Numbe (ISRCTN) eg-
is y (h p://www.is c n.com/), which con ains he basic se o da a i ems deemed essen ial o
desc ibe a s udy a incep ion, as pe he equi emen s se ou by he Wo ld Heal h O ganiza-
ion, he In e na ional Clinical T ials Regis y Pla o m, and he ICMJE guidelines. These wo
egis ies ep esen he wo majo ecipien s o ial egis a ions wo ldwide [8], while all ial
eco ds in hese da abases a e eely accessible and ha e been assigned a unique ial iden i ie ,
he eby enabling linking ial egis a ions o hei subsequen publica ions.
Howe e , exis ing esea ch shows ha he esul s o s udies a e o en no sha ed publicly in
a imely way and ha be ween 25% and 50% o clinical ials emain unpublished e en se e al
yea s a e comple ion [9–11]. The e a e many possible easons behind he delayed o non-
publica ion o esul s om clinical ials, including lack o incen i e o dissemina e nega i e
indings, ime cons ain s, limi ed esou ces, changing esea ch in e es s, o e en ailu e o
ha e an a icle accep ed by a jou nal. Impo an ly, ime-lags in he dissemina ion o esul s
may ha e ad e se consequences o he p ac ice o e idence based medicine and o public
heal h [12]. The non-publica ion o ial esul s also iola es an e hical obliga ion ha ial
in es iga o s ha e owa ds ial pa icipan s [13]. E en i ials do e en ually ge published
yea s la e , i may be oo la e, and he esul s may ha e less ele ance because o he apid
changes in he landscape o e idence.
Al hough se e al s udies ha e es ima ed he p opo ion o incomple e o selec i e epo ing
in a ious medical special ies [14–17], no such assessmen s exis in o hodon ics. A p e ious
s udy [18] p o ided an o e iew o egis e ed ials in o hodon ics up o 2014, bu was limi ed
o desc ip i e analysis o hei egis a ions and did no assess which we e e en ually pub-
lished. Aim o he p esen s udy was o assess he publica ion a e o egis e ed o hodon ic
andomized clinical ials and o assess cha ac e is ics ela ed o hei publica ion iming.
Ma e ials and me hods
S udy sample
The p o ocol o he p esen s udy was d a ed p io o s udy ini ia ion, bu was no egis e ed
in PROSPERO, as i did no mee PROSPERO’s p e equisi e o ha ing clinical connec ion o
he ials’ esul s. Fo his s udy wo au ho s (SNP and GNA) sea ched independen ly wo
online egis ies o andomized ials, ClinicalT ials.go and ISRCTN, up o Janua y 2017. As
we in ended o assess he publica ion a e o hese ials, only egis a ions o ials ma ked in
he egis ies as comple ed we e included. Regis a ions o non- andomized o non-o hodon-
ic ials we e excluded, while any egis a ions pe aining o he same ial we e g ouped
oge he .
The same wo au ho s (SNP and GNA) subsequen ly sea ched independen ly in Janua y
2017 o any publica ions o igina ing om he comple ed egis e ed ials using a p e ious
comp ehensi e loca ing p o ocol [19]. Ini ially, he publica ion ield o he ial p o ocol
Regis a ion and publica ion o ials in o hodon ics
PLOS ONE | h ps://doi.o g/10.1371/jou nal.pone.0182785 Augus 4, 2017 2 / 13
egis a ion was sea ched o any linked e e ences. Secondly, he unique ial iden i ie
assigned wi hin each egis a ion was used o sea ch he web h ough Google (h ps://www.
google.com), Google Schola (h ps://schola .google.com/), and MEDLINE ia Pubmed
(h ps://www.ncbi.nlm.nih.go /pubmed/). Finally, i no co esponding publica ions could be
aced, he names o all in es iga o s lis ed in he ial p o ocol as p incipal in es iga o o o h-
e wise we e used o sea ches in MEDLINE, combining hem wi h he keywo d o hodon
(Table A in S1 File). Manually-iden i ied publica ions we e judged as o igina ing om a spe-
ci ic ial egis a ion, i ei he (i) he unique egis a ion iden i ie was epo ed wi hin he
ial publica ion o (ii) he used au ho names o e lapped be ween p o ocol and publica ion,
he ial was andomized and on he same subjec as he p o ocol, and pa ien en ollmen in
he publica ion ma ched he ial p o ocol desc ip ion. Only publica ions om scien i ic jou -
nals we e included, while ial publica ions in he o m o heses/disse a ions we e excluded,
as hey ollow conside ably di e en publica ion pa hways and a e no subjec o he same pee
e iew p ocedu es as jou nal pape s. The ial’s Pubmed Unique Iden i ie (PMID) (o manual
unique iden i ie s in case ha didn’ exis ) was assigned o each iden i ied ial publica ion o
iden i ica ion pu poses.
Da a ex ac ion
The same wo au ho s (SNP and GNA) independen ly ex ac ed da a on he le el o ial egis-
a ion and ial publica ion, using p e-de ined and calib a ed ex ac ion o ms. Ex ac ed da a
om he ial’s egis a ion included egis y, egis a ion numbe , clinal se ing (uni e si y
clinic, hospi al, o p i a e p ac ice), geog aphic in o ma ion (coun y and con inen ), ial
s a - and end-da e, sponso (in e nal, go e nmen , comme cial, o o he ), egis a ion’s im-
ing ( egis e ed be o e o a e ial ini ia ion [20]), ial na u e (single-cen e o mul icen e ),
ou come ype (pa ien - epo ed o in es iga o -assessed), age o eligible pa ien s (child en,
adul s, o mixed), and ial size (a bi a ily ca ego ized as o <100 pa ien s pe ial a m
based on empi ical da a [21]). Ex ac ed da a om he ial’s publica ion included, PMID, pub-
lica ion da e, numbe o iden i ied publica ions om he same ial, jou nal name, jou nal
publica ion ype (wi h o wi hou elec onic publica ion ahead o p in ), and ial indings
(judged om he abs ac as posi i e, no posi i e, o unclea ). In o ma ion abou he a ilia-
ion and geog aphical loca ion o a ial was based on he pe son lis ed as p incipal in es iga o
o each ial o he esponsible pa y, i no p incipal in es iga o was lis ed. We measu ed he
ime om ial comple ion o publica ion by calcula ing he du a ion o ime (in mon hs). The
ial comple ion da e was de e mined om he ial’s egis a ion, while he ea lies da e a ial
eme ged in MEDLINE was adop ed as i s publica ion da e. Fo wo ials ha we e no lis ed
in MEDLINE publica ion da e was he i s day o he jou nal publica ion issue’s mon h. I a
ial publica ion pe ained o p elimina y esul s o a ial and no he inal esul s o he ial’s
p ima y ou come, he ial was coded as unpublished. Fo all ials wi hou any iden i ied pub-
lica ions we calcula ed he ollow-up ime as he du a ion in mon hs be ween ial comple ion
and end da e o ou s udy (Janua y 12, 2017).
S a is ical analysis
We conduc ed a desc ip i e analysis calcula ing equencies o bina y ou comes o medians,
In e qua ile Ranges (IQRs), and anges o con inuous ou comes, due o skewness o he
la e . Simple di e ences in he ial publica ion a e and comple ion- o-publica ion ime
acco ding o he a ious desc ip i e cha ac e is ics we e in es iga ed wi h chi-squa e /Fishe
exac and K uskal-Wallis es s, espec i ely. Fo he analyses, geog aphic egions (con inen )
we e me ged oge he , i less han 10 ials o a oid da a hinning. In addi ion, we e alua ed
Regis a ion and publica ion o ials in o hodon ics
PLOS ONE | h ps://doi.o g/10.1371/jou nal.pone.0182785 Augus 4, 2017 3 / 13
publica ion a e o included egis e ed ials using Kaplan-Meie analysis a e checking o
assump ions and assessed in luencing ac o s wi h g aphical inspec ion and log- ank es s.
Fo he su i al analyses he comple ion- o-publica ion ime o published ials (o he com-
ple ion- o-Janua y 2017 ime o unpublished ials) we e used as ollow-up pe iods, while all
ials ha emained unpublished we e censo ed. All analyses o da a (S1 Da ase ) we e pe -
o med in S a a e sion SE 14 (S a aCo p LP, College S a ion, TX) wi h a le el o signi icance
se a 5%.
Resul s
We iden i ied a o al o 266 egis e ed ials in o hodon ic, 130 o which we e comple ed in
Janua y 2017, and we e assessed o eligibili y in he p esen s udy (Fig 1; Table B in S1 File).
Finally, a o al o 50 egis e ed ials we e judged as ineligible, lea ing 80 egis e ed ials ha
we e inally included in his s udy. These pe ained o 80 andomized ials, he majo i y
(59%) o which o igina ed om Eu ope and speci ically om he Uni ed Kingdom (44%).
They we e ini ia ed be ween 1997–2015 and we e comple ed be ween 2003–2016 (Table 1).
F om he iden i ied ials, hal o hem (50%) had no ex e nal inancial suppo , while only
he mino i y (8%) included mul iple ial si es (Table 2). The median numbe o planned
pa ien s o be en olled in he ial was 50 pa ien s (IQR: 30–90 pa ien s; Table 3), while only
23% o he ials had a la ge sample size (100 pa ien s). In e es ingly, only 24% o ial p o o-
cols we e egis e ed p ospec i ely and he as majo i y o ials (76%) we e egis e ed a e
ial ini ia ion.
As a as publica ion a e o he egis e ed ials is conce ned, only 33 (41%) o he 80 iden i-
ied comple ed ials including a leas 3839 pa ien s had been published in jou nals a he ime
his s udy was comple ed, wi h 10% o ials being published in mul iple pape s (Table 2). The
majo i y o egis e ed ials we e published in special y jou nals and in jou nals ha p o ided
elec onic publica ion ahead o p in op ion (64% and 55% espec i ely). Finally, abou equal
pa s o he 33 published ials epo ed posi i e and non-posi i e indings (42% and 45%,
espec i ely), while esul s we e inconclusi e in he emaining 4 ials (12%). No associa ion
be ween publica ion a e and cha ac e is ics o he egis e ed ials could be ound (Table 3).
The single excep ion was he geog aphic loca ion o he ial, wi h egis e ed ials om No h
Ame ica and A ica being published less o en han ials om o he con inen s. Howe e ,
he emaining 47 (59%) egis e ed and comple ed ials, including a leas 2355 andomized
pa ien s, emained unpublished a he ime o he p esen s udy.
Among he 33 comple ed ials ha we e e en ually published, 10 (30%), 18 (55%), 27
(82%), 29 (88%), and 30 (91%) o hem we e published wi hin 12, 24, 36, 48, and 60 mon hs
a e ial comple ion, espec i ely (Table 2). The median ime om comple ion o publica ion
was 20.1 mon hs wi h an IQR o 9.1–31.6 mon hs) (Table 4). Conside able di e ences in he
comple ion- o-publica ion ime we e ound acco ding o egis y, sponso ype, pa ien age,
and jou nal (Table C in S1 File), wi h ials om ClinicalT ials.go , in e nally sponso ed, wi h
adul o mixed pa ien popula ions, and ials submi ed in non-special y jou nals we e pub-
lished as e han he es .
The Kaplan-Meie es ima es o he publica ion a e o he 80 included ials indica ed ha
mos o hem we e published du ing he i s 24 o 48 mon hs a e comple ion (Figu e A in S2
File). On he o he side, abou 60 mon hs ( i e yea s) a e comple ion no conside able publi-
ca ion ac i i y was seen. Di e ences in he su i al cu es can be seen in Figu es B-M in S2
File. T ials egis e ed in ClinicalT ials.go seemed o be published as e and mo e o en han
ials egis e ed in ISRCTN (Figu e B in S2 File), while conside able di e ences in he publica-
ion a e we e seen ac oss con inen s (Figu e E in S2 File). Addi ionally, ials wi h adul
Regis a ion and publica ion o ials in o hodon ics
PLOS ONE | h ps://doi.o g/10.1371/jou nal.pone.0182785 Augus 4, 2017 4 / 13
pa ien s o ials wi h unspeci ied pa ien popula ions seemed o be published less o mo e
slowly han ials on child en (Figu e I in S2 File). Finally, among he 33 published ials, ials
in non-special y jou nals seemed o ge published as e han ial publica ions in special y
jou nals (Figu e K in S2 File).
As he majo i y (30 ou o 33 ials; 91%) o comple ed and published ials we e published
wi hin 5 yea s om hei comple ion (Table 2), a ee-pe iod o 5 yea s om comple ion was
allowed o all 80 iden i ied and comple ed ials. Howe e , abou one hi d (n = 22; 28%) o
comple ed ials s ill emained unpublished, e en hough 5 yea s had elapsed om ial com-
ple ion, wi h small chances o he ial inally ge ing published.
Fig 1. Flowdiag am o he s udy selec ion.
h ps://doi.o g/10.1371/jou nal.pone.0182785.g001
Regis a ion and publica ion o ials in o hodon ics
PLOS ONE | h ps://doi.o g/10.1371/jou nal.pone.0182785 Augus 4, 2017 5 / 13

Discussion
Summa y o e idence
The p esen s udy assessed he publica ion a e as well as he comple ion- o-publica ion ime
o all andomized ials in o hodon ics ha had been egis e ed in ClinicalT ials.go and
ISRCTN and had been iled as ‘comple ed’ up o Janua y 2017.
The esul s indica ed ha a he ime o comple ion o he p esen s udy (Janua y 2017)
59% o all egis e ed and comple ed ials had no been published, which co esponded o a
leas 2355 included pa ien s (some ials did no epo he planned pa ien sample). This
ag ees wi h simila s udies on he biomedical li e a u e ha epo non-publica ion a es o
29% [15], 34% [16], 50% [17], and 54% [14].
As a as ime o publica ion is conce ned, he esul s indica ed ha he median comple-
ion- o-publica ion ime was 20.1 mon hs (1.6 yea s). This also is simila o he indings o p e-
ious in es iga ions, which epo a median comple ion- o-publica ion ime o 28.8 mon hs
(2.4 yea s) [22]. Addi ionally, su i al analysis indica ed ha mos o he ials we e published
Table 1. Demog aphics o he included egis e ed ial p o ocols.
N
a
N %
Regis e ClinicalT ials.go 80 45 56%
ISRCTN 35 44%
Coun y Aus ia 80 1 1%
Belgium 1 1%
B azil 5 6%
Canada 2 3%
China 1 1%
Colombia 1 1%
Egyp 1 1%
F ance 2 3%
Ge many 4 5%
Hong Kong 1 1%
India 3 4%
I an 1 1%
I aly 2 3%
Kuwai 1 1%
Sweden 1 1%
Sy ia 4 5%
Uni ed Kingdom 35 44%
Uin ed S a es o Ame ica 12 15%
No epo ed 2 3%
Se ing Uni e si y 80 63 79%
P i a e 1 1%
Hospi al 16 20%
Con inen Eu ope 80 47 59%
Asia 11 14%
No h Ame ica 14 18%
Sou h Ame ica & A ica 8 10%
ISRCTN = In e na ional S anda d Randomised Con olled T ial Numbe ; N
a
= eligible ials ials included in
he assessmen o his ac o ; N = ials in each ac o ca ego y.
h ps://doi.o g/10.1371/jou nal.pone.0182785. 001
Regis a ion and publica ion o ials in o hodon ics
PLOS ONE | h ps://doi.o g/10.1371/jou nal.pone.0182785 Augus 4, 2017 6 / 13
Table 2. Cha ac e is ics o he included egis e ed ial p o ocols (bina y a iables).
Fac o Ca ego y N
a
N %
Sponso In e nal 80 40 50%
Go e nmen 21 26%
Comme cial 10 13%
O he 9 11%
Regis a ion P ospec i e 80 19 24%
Re ospec i e 61 76%
Ou come Pa ien - epo ed 79 6 8%
In es iga o -asse ed 73 92%
La ge ial (100 pa ien s pe ial a m) Yes 71 5 7%
No 66 93%
Mul icen e ial Yes 80 6 8%
No 74 93%
Eligible pa ien s Child en 80 29 36%
Adul s 8 10%
Mixed 29 36%
No speci ied 14 18%
T ial published Yes 80 33 41%
No 47 59%
Publica ion a e a e ial comple ion Wi hin 12 mon hs 33 10 30%
Wi hin 24 mon hs 18 55%
Wi hin 36 mon hs 27 82%
Wi hin 48 mon hs 29 88%
Wi hin 60 mon hs 30 91%
Publica ions om egis e ed ial p o ocol None 80 47 59%
One 25 31%
Two 5 6%
Th ee 3 4%
T ials emaining unpublished a e 5 yea s Yes 80 22 28%
No 58 72%
Jou nal Am J O hod Den o acial O hop 33 8 24%
Angle O hod 1 3%
B J O al Maxillo ac Su g 1 3%
Ca ies Res 1 3%
Eu J O hod 6 18%
In J Paedia Den 1 3%
J Am Den Assoc 1 3%
J Clin Diagn Res 1 3%
J Con emp Den P ac 1 3%
J Den Res 3 9%
J Indian O hod Soc 1 3%
J O hod 5 15%
J Pha m Biomed Sci 1 3%
Pho omed Lase Su g 1 3%
Sci Rep 1 3%
Jou nal ype Special y (o hodon ic) 33 21 64%
Non-special y 12 36%
Jou nal wi h E-publica ion ahead o p in Yes 33 18 55%
(Con inued)
Regis a ion and publica ion o ials in o hodon ics
PLOS ONE | h ps://doi.o g/10.1371/jou nal.pone.0182785 Augus 4, 2017 7 / 13
wi hin he i s 24–48 mon hs (2–4 yea s) a e he ial’s comple ion. A e abou 60 mon hs
(5 yea s) he ial publica ion a e was minimal, wi h only 3 ials (9% o all published ials)
being published his ime poin . This is simila o he esul s o Chapman e al. [16] ha indi-
ca ed ha he majo i y o published ials (73%) ge s published wi hin 48 mon hs a e ial
comple ion. This seems o also ag ee wi h Li as e al. [23] epo ing ha only hal o s udy
abs ac s p esen ed in o hodon ic cong esses ( he e o e pe aining o comple ed s udies)
Table 2. (Con inued)
Fac o Ca ego y N
a
N %
No 15 45%
T ial esul s Posi i e 33 15 42%
No posi i e 14 45%
Unclea 4 12%
N
a
= eligible ials ials included in he assessmen o his ac o ; N = ials in each ac o ca ego y.
h ps://doi.o g/10.1371/jou nal.pone.0182785. 002
Table 3. C oss- abula ion o subsequen ial publica ion and p o ocol cha ac e is ics.
Fac o Ca ego y Published
N (%)
Unpublished
N (%)
P*
Regis y ClinicalT ials.go 20 (44%) 25 (56%) 0.51
ISRCTN 13 (37%) 22 (63%)
Sponso In e nal 14 (35%) 26 (65%) 0.30
Go e nmen 10 (48%) 11 (52%)
Comme cial 3 (30%) 7 (70%)
O he 6 (67%) 3 (33%)
A ilia ion Uni e si y 26 (41%) 37 (59%) 1.00
P i a e p ac ice 0 (0%) 1 (100%)
Hospi al 7 (78%) 9 (22%)
Con inen Eu ope 20 (43%) 27 (57%) 0.30
Asia 8 (73%) 3 (27%)
N. Ame ica 2 (14%) 12 (86%)
S. Ame ica & A ica 3 (38%) 5 (62%)
Regis a ion P ospec i ely 26 (43%) 35 (57%) 0.66
Re ospec i ely 7 (37%) 12 (63%)
Ou come Pa ien - epo ed 31 (42%) 42 (58%) 1.00
Doc o -assessed 2 (33%) 4 (67%)
Mul icen e ial Yes 2 (33%) 4 (67%) 1.00
No 31 (42%) 42 (58%)
Pa ien s Child en 14 (48%) 15 (52%) 0.07
Adul s 2 (25%) 6 (75%)
Mixed 15 (52%) 14 (48%)
No speci ied 2 (14%) 12 (86%)
La ge ial Yes 4 (80%) 1 (20%) 0.17
No 28 (42%) 38 (58%)
ISRCTN = In e na ional S anda d Randomised Con olled T ial Numbe .
* om chi-squa e (o Fishe ’s exac es , when mo e han 20% o he cells ha e expec ed equency less han i e o a leas one is null)
h ps://doi.o g/10.1371/jou nal.pone.0182785. 003
Regis a ion and publica ion o ials in o hodon ics
PLOS ONE | h ps://doi.o g/10.1371/jou nal.pone.0182785 Augus 4, 2017 8 / 13
each ull publica ion, wi h a median p esen a ion- o-publica ion ime o 16 mon hs (1.3
yea s).
Se e al egis y-, ial-, o pa ien - ela ed cha ac e is ics seemed o a ec he publica ion
a e o included egis e ed ials, as seen h ough he Kaplan-Meie su i al es ima es and he
log- ank es s (Table D in S1 File; Figu es B-M in S2 File). Fo one, conside able di e ences
we e obse ed be ween ials egis e ed in ClinicalT ials.go and hose egis e ed in ISRCTN,
wi h ials egis e ed in he la e being published less o en and la e . This migh indica e ha
a ue di e ence exis s in he publica ion o comple ed ials, bu i migh also be associa ed
wi h he conside able geog aphic di e ences in he con en o he wo egis ies, as ISRCTN
included ials p ima ily om he Uni ed Kingdom, while ClinicalT ials.go had a wide con-
ibu ion spec um (Figu e N in S2 File).
Coun ing only unpublished ials wi h a ollow-up pe iod o mo e han 5 yea s a e ial
comple ion o allow o a ee pe iod o be published, indica ed ha 28% (n = 22) o iden i ied
ials s ill emained unpublished. This is o impo ance as, based on p esen esul s, he chance
o hose ials being e en ually published is small. This ep esen s a was e o esou ces as well
as a gap in he exis ing esea ch e idence in o hodon ics ha can ha e a di ec impac on sys-
ema ic e iews o clinical ials and subsequen ly on clinical decision making. Fo example,
se e al ials on new appliances o no el adjunc p ocedu es aimed o expedi e o hodon ic
ea men emain o he p esen unpublished (Table E in S1 File), which means ha exis ing
sys ema ic e iews on his subjec [24–27] migh no e lec he ac ual e idence base.
The e a e se e al s eps ha could be implemen ed owa d imp o emen o ial egis a ion
and ial publica ion p ac ices. Agencies unding clinical ials could implemen s ic e su -
eillance sys ems o ial publica ion a e and u ge esea che s o publish he esul s o hei
ials, no ma e how posi i e o nega i e hese migh seem. Au ho s a e encou aged o egis e
ials p io o ial ini ia ion. In he p esen s udy, he majo i y (76%) o andomized ials
we e egis e ed e ospec i ely, some hing ha has also been seen in o he ields o medicine
[20], bu does nei he co espond o he no ion o a p io i ial egis a ion no does i sa e-
gua d agains selec i e epo ing. Edi o s o o hodon ic jou nals should a oid judging ial
submissions om he a ac i eness o hei indings and should pu sue publica ion o ials
wi h nega i e esul s. Fu he mo e, edi o s can indi ec ly p omo e ial egis a ion by using i
as a p e equisi e o a ial o be conside ed o publica ion in he jou nals hey manage. The
ICMJE changed policy in 2005 o adop his [7], which esul ed in an inc ease o ial egis a-
ion [8]. This equi emen was la e inco po a ed in o he ICMJE’s “uni o m equi emen s o
manusc ip s submi ed o biomedical jou nals,” along wi h he upda ed CONSORT 2010 s a e-
men o he epo ing o andomized con olled ials [28]. E en hough a la ge pa o medi-
cal jou nals equi es ials o be egis e ed [29], he landscape in o hodon ics s ill emains
bleak: al hough hal (5 ou o 10) o o hodon ic jou nals men ion egis a ion o andomized
clinical ials a hei ‘Ins uc ions o au ho s’ websi es, only one (Jou nal o O hodon ics)
wo ds his explici ly as a equi emen o publica ion.
Table 4. Cha ac e is ics o he included egis e ed ial p o ocols (con inuous a iables).
Ou come Ex ac ed om N
a
Mean (SD) Median (IQR) Range
Repo ed sample size (pa ien s) P o ocol 71 87.2 (138.4) 50.0 (30.0–90.0) 8.0–1000.0
T ial du a ion (mon hs) P o ocol 80 29.5 (22.4) 24.3 (15.2–36.5) 0.9–124.8
Comple ion- o-publica ion (mon hs) P o ocol / publica ion 33 24.5 (18.0) 20.1 (9.1–31.6) 1.8–65.0
Mean ollow-up o ial p o ocol o he p esen s udy (mon hs) P o ocol / publica ion 80 47.7 (45.8) 28.4 (13.0–64.7) 1.8–166.6
SD = s anda d de ia ion; IQR = in e qua ile ange (Q1-Q3).
h ps://doi.o g/10.1371/jou nal.pone.0182785. 004
Regis a ion and publica ion o ials in o hodon ics
PLOS ONE | h ps://doi.o g/10.1371/jou nal.pone.0182785 Augus 4, 2017 9 / 13