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BMC Medical Research Methodology
Published in: BMC Medical Research Methodology 1/2014

Open Access 01-12-2014 | Research article

Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study

Authors: Violaine Smaïl-Faugeron, Hélène Fron-Chabouis, Frédéric Courson, Pierre Durieux

Published in: BMC Medical Research Methodology | Issue 1/2014

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Abstract

Background

Split-mouth randomized controlled trials (RCTs) are popular in oral health research. Meta-analyses frequently include trials of both split-mouth and parallel-arm designs to derive combined intervention effects. However, carry-over effects may induce bias in split- mouth RCTs. We aimed to assess whether intervention effect estimates differ between split- mouth and parallel-arm RCTs investigating the same questions.

Methods

We performed a meta-epidemiological study. We systematically reviewed meta- analyses including both split-mouth and parallel-arm RCTs with binary or continuous outcomes published up to February 2013. Two independent authors selected studies and extracted data. We used a two-step approach to quantify the differences between split-mouth and parallel-arm RCTs: for each meta-analysis. First, we derived ratios of odds ratios (ROR) for dichotomous data and differences in standardized mean differences (∆SMD) for continuous data; second, we pooled RORs or ∆SMDs across meta-analyses by random-effects meta-analysis models.

Results

We selected 18 systematic reviews, for 15 meta-analyses with binary outcomes (28 split-mouth and 28 parallel-arm RCTs) and 19 meta-analyses with continuous outcomes (28 split-mouth and 28 parallel-arm RCTs). Effect estimates did not differ between split-mouth and parallel-arm RCTs (mean ROR, 0.96, 95% confidence interval 0.52–1.80; mean ∆SMD, 0.08, -0.14–0.30).

Conclusions

Our study did not provide sufficient evidence for a difference in intervention effect estimates derived from split-mouth and parallel-arm RCTs. Authors should consider including split-mouth RCTs in their meta-analyses with suitable and appropriate analysis.
Appendix
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Literature
1.
Antczak-Bouckoms AA, Tulloch JF, Berkey CS: Split-mouth and cross-over designs in dental research. J Clin Periodontol. 1990, 17 (7 Pt 1): 446-453.CrossRefPubMed
2.
Pandis N, Walsh T, Polychronopoulou A, Katsaros C, Eliades T: Split-mouth designs in orthodontics: an overview with applications to orthodontic clinical trials. Eur J Orthod. 2013, 35 (6): 783-789. 10.1093/ejo/cjs108.CrossRefPubMed
3.
Ramfjord SP, Nissle RR, Shick RA, Cooper H: Subgingival curettage versus surgical elimination of periodontal pockets. J Periodontol. 1968, 39 (3): 167-175.CrossRefPubMed
4.
Hujoel PP, DeRouen TA: Validity issues in split-mouth trials. J Clin Periodontol. 1992, 19 (9 Pt 1): 625-627.CrossRefPubMed
5.
Hujoel PP, Loesche WJ: Efficiency of split-mouth designs. J Clin Periodontol. 1990, 17 (10): 722-728. 10.1111/j.1600-051X.1990.tb01060.x.CrossRefPubMed
6.
Donner A, Eliasziw M: Application of matched pair procedures to site-specific data in periodontal research. J Clin Periodontol. 1991, 18 (10): 755-759. 10.1111/j.1600-051X.1991.tb00068.x.CrossRefPubMed
7.
Hujoel PP: Design and analysis issues in split mouth clinical trials. Community Dent Oral Epidemiol. 1998, 26 (2): 85-86. 10.1111/j.1600-0528.1998.tb01932.x.CrossRefPubMed
8.
Vaeth M, Poulsen S: Comments on a commentary: statistical evaluation of split mouth caries trials. Community Dent Oral Epidemiol. 1998, 26 (2): 80-83. 10.1111/j.1600-0528.1998.tb01930.x. discussion 84CrossRefPubMed
9.
Lesaffre E, Philstrom B, Needleman I, Worthington H: The design and analysis of split-mouth studies: what statisticians and clinicians should know. Stat Med. 2009, 28 (28): 3470-3482. 10.1002/sim.3634.CrossRefPubMed
10.
Lee E, Dobbins M, Decorby K, McRae L, Tirilis D, Husson H: An optimal search filter for retrieving systematic reviews and meta-analyses. BMC Med Res Methodol. 2012, 12: 51-10.1186/1471-2288-12-51.CrossRefPubMedPubMedCentral
11.
Savović J, Harris RJ, Wood L, Beynon R, Altman D, Als-Nielsen B, Balk EM, Deeks J, Gluud LL, Gluud C, John PA, Ioannidis JPA, Jűni P, Moher D, Pildal J, Kenneth F, Schulz KF, Sterne JAC: Development of a combined database for meta- epidemiological research. Res Synth Method. 2010, 1 (3–4): 212-225.CrossRef
12.
Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A: Meta- analyses involving cross-over trials: methodological issues. Int J Epidemiol. 2002, 31 (1): 140-149. 10.1093/ije/31.1.140.CrossRefPubMed
13.
Follmann D, Elliott P, Suh I, Cutler J: Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol. 1992, 45 (7): 769-773. 10.1016/0895-4356(92)90054-Q.CrossRefPubMed
14.
Becker M, Balagtas C: Marginal modelling of binary cross-over data. Biometrics. 1993, 49 (4): 997-1009. 10.2307/2532242.CrossRefPubMed
15.
Stedman MR, Curtin F, Elbourne DR, Kesselheim AS, Brookhart MA: Meta-analyses involving cross-over trials: methodological issues. Int J Epidemiol. 2011, 40 (6): 1732-1734. 10.1093/ije/dyp345.CrossRefPubMed
16.
Borenstein M, Cooper H, Hedges L, Valentine J: Effect sizes for continuous data. The Handbook of Research Synthesis and Meta-Analysis. Edited by: Cooper H, Hedges L, Valentine J. 2009, New York: Russel Sage Foundation, 221-235.
17.
Sterne JA, Juni P, Schulz KF, Altman DG, Bartlett C, Egger M: Statistical methods for assessing the influence of study characteristics on treatment effects in ‘meta-epidemiological’ research. Stat Med. 2002, 21 (11): 1513-1524. 10.1002/sim.1184.CrossRefPubMed
18.
Annibali S, Bignozzi I, Cristalli MP, Graziani F, La Monaca G, Polimeni A: Peri- implant marginal bone level: a systematic review and meta-analysis of studies comparing platform switching versus conventionally restored implants. J Clin Periodontol. 2012, 39 (11): 1097-1113. 10.1111/j.1600-051X.2012.01930.x.CrossRefPubMed
19.
Atieh MA: Photodynamic therapy as an adjunctive treatment for chronic periodontitis: a meta-analysis. Lasers Med Sci. 2010, 25 (4): 605-613. 10.1007/s10103-009-0744-6.CrossRefPubMed
20.
Brignardello-Petersen R, Carrasco-Labra A, Araya I, Yanine N, Beyene J, Shah P: Is adjuvant laser therapy effective for preventing pain, swelling, and trismus after surgical removal of impacted mandibular third molars? a systematic review and meta-analysis. J Oral Maxillofac Surg. 2012, 70 (8): 1789-1801. 10.1016/j.joms.2012.01.008.CrossRefPubMed
21.
Cairo F, Pagliaro U, Nieri M: Treatment of gingival recession with coronally advanced flap procedures: a systematic review. J Clin Periodontol. 2008, 35 (8): 136-162.CrossRefPubMed
22.
Carrasco-Labra A, Brignardello-Petersen R, Yanine N, Araya I, Guyatt G: Secondary versus primary closure techniques for the prevention of postoperative complications following removal of impacted mandibular third molars: a systematic review and meta-analysis of randomized controlled trials. J Oral Maxillofac Surg. 2012, 70 (8): e441-457. 10.1016/j.joms.2012.03.017.CrossRefPubMed
23.
Chambrone L, Sukekava F, Araujo MG, Pustiglioni FE, Chambrone LA, Lima LA: Root coverage procedures for the treatment of localised recession-type defects. Cochrane Database Syst Rev. 2009, 2: CD007161
24.
Del Fabbro M, Bortolin M, Taschieri S, Weinstein R: Is platelet concentrate advantageous for the surgical treatment of periodontal diseases? a systematic review and meta-analysis. J Periodontol. 2011, 82 (8): 1100-1111. 10.1902/jop.2010.100605.CrossRefPubMed
25.
Esposito M, Grusovin MG, Achille H, Coulthard P, Worthington HV: Interventions for replacing missing teeth: different times for loading dental implants. Cochrane Database Syst Rev. 2009, 1: CD003878
26.
Esposito M, Grusovin MG, Papanikolaou N, Coulthard P, Worthington HV: Enamel matrix derivative (Emdogain(R)) for periodontal tissue regeneration in intrabony defects. Cochrane Database Syst Rev. 2009, CD003875-4
27.
Esposito M, Maghaireh H, Grusovin MG, Ziounas I, Worthington HV: Interventions for replacing missing teeth: management of soft tissues for dental implants. Cochrane Database Syst Rev. 2012, 2: CD006697
28.
Fleming PS, Johal A, Pandis N: Self-etch primers and conventional acid-etch technique for orthodontic bonding: a systematic review and meta-analysis. Am J Orthod Dentofacial Orthop. 2012, 142 (1): 83-94. 10.1016/j.ajodo.2012.02.023.CrossRefPubMed
29.
Imai P, Yu X, MacDonald D: Comparison of interdental brush to dental floss for reduction of clinical parameters of periodontal disease: a systematic review. Can J Dental Hygiene. 2012, 46 (1): 63-78.
30.
Lodi G, Figini L, Sardella A, Carrassi A, Del Fabbro M, Furness S: Antibiotics to prevent complications following tooth extractions. Cochrane Database Syst Rev. 2012, 11: CD003811-PubMed
31.
Mickenautsch S, Yengopal V: Absence of carious lesions at margins of glass- ionomer cement and amalgam restorations: an update of systematic review evidence. BMC Res Notes. 2011, 4: 58-10.1186/1756-0500-4-58.CrossRefPubMedPubMedCentral
32.
Muller-Bolla M, Lupi-Pegurier L, Tardieu C, Velly AM, Antomarchi C: Retention of resin-based pit and fissure sealants: a systematic review. Community Dent Oral Epidemiol. 2006, 34 (5): 321-336. 10.1111/j.1600-0528.2006.00319.x.CrossRefPubMed
33.
Needleman IG, Worthington HV, Giedrys-Leeper E, Tucker RJ: Guided tissue regeneration for periodontal infra-bony defects. Cochrane Database Syst Rev. 2006, CD001724-2
34.
Ricketts DN, Kidd EA, Innes N, Clarkson J: Complete or ultraconservative removal of decayed tissue in unfilled teeth. Cochrane Database Syst Rev. 2006, CD003808-3
35.
Sgolastra F, Severino M, Gatto R, Monaco A: Effectiveness of diode laser as adjunctive therapy to scaling root planning in the treatment of chronic periodontitis: a meta-analysis. Lasers Med Sci. 2013, 28 (5): 1393-1402. 10.1007/s10103-012-1181-5.CrossRefPubMed
36.
Yong SL, Coulthard P, Wrzosek A: Supplemental perioperative steroids for surgical patients with adrenal insufficiency. Cochrane Database Syst Rev. 2012, 12: CD005367
37.
Lesaffre E, Garcia Zattera MJ, Redmond C, Huber H, Needleman I: Reported methodological quality of split-mouth studies. J Clin Periodontol. 2007, 34 (9): 756-761. 10.1111/j.1600-051X.2007.01118.x.CrossRefPubMed
38.
Savovic J, Jones HE, Altman DG, Harris RJ, Juni P, Pildal J, Als-Nielsen B, Balk EM, Gluud C, Gluud LL, Ioannidis JP, Schultz KF, Beynon R, Welton NJ, Wood L, Moher D, Deeks JJ, Sterne JAC: Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Ann Intern Med. 2012, 157 (6): 429-438. 10.7326/0003-4819-157-6-201209180-00537.CrossRefPubMed
39.
Dechartres A, Boutron I, Trinquart L, Charles P, Ravaud P: Single-center trials show larger treatment effects than multicenter trials: evidence from a meta - epidemiologic study. Ann Intern Med. 2011, 155 (1): 39-51. 10.7326/0003-4819-155-1-201107050-00006.CrossRefPubMed
40.
Goodman S, Dickersin K: Metabias: a challenge for comparative effectiveness research. Ann Intern Med. 2011, 155 (1): 61-62. 10.7326/0003-4819-155-1-201107050-00010.CrossRefPubMed
41.
Lathyris DN, Trikalinos TA, Ioannidis JP: Evidence from crossover trials: empirical evaluation and comparison against parallel arm trials. Int J Epidemiol. 2007, 36 (2): 422-430. 10.1093/ije/dym001.CrossRefPubMed
42.
Chan AW, Altman DG: Epidemiology and reporting of randomised trials published in PubMed journals. Lancet. 2005, 365 (9465): 1159-1162. 10.1016/S0140-6736(05)71879-1.CrossRefPubMed
43.
Hopewell S, Dutton S, Yu LM, Chan AW, Altman DG: The quality of reports of randomised trials in 2000 and 2006: comparative study of articles indexed in PubMed. BMJ. 2010, 340: c723-10.1136/bmj.c723.CrossRefPubMedPubMedCentral
44.
Greene D, Koch RJ, Goode RL: Efficacy of octyl-2-cyanoacrylate tissue glue in blepharoplasty: a prospective controlled study of wound-healing characteristics. Arch Facial Plast Surg. 1999, 1 (4): 292-296. 10.1001/archfaci.1.4.292.CrossRefPubMed
45.
Davey J, Turner RM, Clarke MJ, Higgins JP: Characteristics of meta-analyses and their component studies in the cochrane database of systematic reviews: a cross-sectional, descriptive analysis. BMC Med Res Methodol. 2011, 11: 160-10.1186/1471-2288-11-160.CrossRefPubMedPubMedCentral
Metadata
Title
Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study
Authors
Violaine Smaïl-Faugeron
Hélène Fron-Chabouis
Frédéric Courson
Pierre Durieux
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Medical Research Methodology / Issue 1/2014
Electronic ISSN: 1471-2288
DOI
https://doi.org/10.1186/1471-2288-14-64

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