The Treatment Effects Of Invisalign Orthodontic Aligners

1724 JADA, Vol. 136 http://jada.ada.org December 2005

P R A C T I C A L S C I E N C E

The mission of Practical Science is to spotlight scientific knowledge about the issues and challenges facingtoday’s practicing dentists.

Background. Theauthors conducted a systematic review of theliterature to determinethe treatment effects ofthe Invisalign orthodonticsystem (Align Technology),Santa Clara, Calif.).Types of Studies Reviewed. Theauthors reviewed clinical trials that assessedInvisalign’s treatment effects in nongrowingpatients. They did not consider trialsinvolving surgical or other simultaneous fixedor removable orthodontic treatment interventions. Results. The authors searched electronicdatabases (PubMed, MEDLINE, MEDLINEIn-Process & Other Non-Indexed Citations,Evidence Based Medicine Reviews, EMBASEExcerpta Medica, Thomsen’s ISI Web of Sci-ence and LILACS) with the help of a seniorhealth sciences librarian. They used“Invisalign” as the sole search term, and 22 documents appeared in the combinedsearch. Thereafter, they used “clinical trials,”“humans” and “Invisalign treatment effects”as abstract selection criteria. Only two pub-lished articles met these inclusion criteria,though after reading the actual articles, theauthors determined that they did not ade-quately evaluate Invisalign treatment effects.Both articles identified methodological issues. Clinical Implications. The inadequatelydesigned studies the authors found repre-sented only a lower level of evidence (level II).Therefore, the authors found that no strongconclusions could be made regarding thetreatment effects of Invisalign appliances.Future prospective randomized clinical trialsare required to support, with sound scientificevidence, the claims about Invisalign’s treat-ment effects. Clinicians will have to rely ontheir Invisalign clinical experience, the opin-ions of experts and the limited published evi-dence when using Invisalign appliances.Key Words. Invisalign; treatment out-comes; orthodontics.

The treatment effects of Invisalignorthodontic alignersA systematic review

MANUEL O. LAGRAVERE, D.D.S., M.Sc.; CARLOSFLORES-MIR, D.D.S., M.Sc., Cert. Ortho., Ph.D.

An orthodontic treatment method based onthe usage of removable, clear semielasticpolyurethane aligners known as Invisalign(Align Technology, Santa Clara, Calif.) hasbeen available since 1997.1 These aligners

are made from a thin, transparent plastic that fits overthe buccal, lingual/palatal and occlusal surfaces of theteeth. They conventionally are worn for a minimum of

20 hours per day and are changedsequentially every two weeks.2

Invisalign has been indicated by itsmanufacturer to be used in adults andadolescents who have fully erupted per-manent dentitions.3 Although thereseems to be a general agreement that itis not indicated for all types of patientsreceiving orthodontic treatment,4 con-troversy exists about the extension ofthe aligners’ treatment indications.Some indicate that they should be usedin orthodontic cases without skeletaldisharmonies with mild crowding,2

whereas others have suggested that Invisalign may besuitable for even moderately complex orthodonticcases.5,6

An evidence-based health care practice aims to pro-vide the best possible treatment based on sound evi-dence.7 It is clear that scientific evidence alone shouldnot automatically dictate the selection of the treatmentoption. It is a combination of values (clinical, personal

A B S T R A C T

The authorsfound that no

strong conclusions

could be maderegarding the

treatmenteffects ofInvisalign

appliances.

JA D

A

CO

NT

I

NU

I N G E D UC

AT

IO

N

✷✷

ARTICLE

4

`

Copyright ©2005 American Dental Association. All rights reserved.

and social) that the clinician analyzes beforeselecting the procedure, which determines if theintervention benefits are worth the cost.8 There-fore, the application of evidence to clinical prac-tice should be related to professional expertiseand patients’ values and needs. A systematicreview evaluates the literature about a specifictopic that has been prepared using a systematicapproach to minimize biases and random errors.9

We conducted a systematic review to determinethe magnitude of the reported treatment effects ofInvisalign based on all available published scien-tific literature that met predetermined minimumcriteria for study design. This information wouldhelp determine which Invisalign treatment indi-cations are supported by the evidence.

METHODS

We conducted a computerized search usingPubMed (1966 to the second week of April 2005),MEDLINE (from 1966 to the first week of April2005), MEDLINE In-Process & Other Non-Indexed Citations (from the first week of April2005 to April 15, 2005), Evidence Based Medicine(EBM) Reviews Database (Cochrane Database ofSystematic Reviews, American College of Physi-cians Journal Club, Database of Abstracts ofReviews of Effects and Cochrane Central Registerof Controlled Trials) (to the first quarter of 2005),EMBASE Excerpta Medica (from 1988 to the firstweek of April 2005), Thomsen’s ISI Web of Sci-ence (1945 to the second week of April 2005) andLILACS (from 1982 to April 2005) databases. Wemade this literature search using “Invisalign” asthe only term, as counseled by a senior librarianspecializing in health sciences databases. Weapplied no language restrictions.

We determined the eligibility of the selectedstudies by reading the abstracts identified by thedatabase searches. To select potentially appro-priate articles from the published abstracts, weused human and clinical trials using Invisalign asa treatment option. We completed this initialselection process independently on the basis ofthe abstract information, then settled any dis-crepancies through discussion. We selected andcollected all the articles that appeared to meetthe initial inclusion criteria based on theirabstracts.

In cases in which specific data were necessaryfor the discussion and was not specified in theabstract, we made efforts to contact the authorsto obtain the required extra information. Before

JADA, Vol. 136 http://jada.ada.org December 2005 1725


making a final decision, we also obtained articlesfor which the abstract did not present enough rel-evant information to enable us to make a sounddecision.

We arrived independently at our final conclu-sions about the appropriateness of the selectedarticles to meet our objective, reading the com-plete articles and then comparing and settlingdiscrepancies by discussion. In addition, we hand-searched the reference lists of the selected articlesfor additional relevant publications that the data-base searches may have missed. In cases in whichspecific data were necessary for the discussionand were not specified in the article, we madeefforts to contact the authors to obtain those data.

RESULTS

We identified 22 abstracts after adding up thedatabase results. From the total abstracts identi-fied, MEDLINE and PubMed obtained thegreatest diversity of abstracts, with 21 each(Table 1). From the other databases, EBMReviews was the only one to present an abstractnot included in either MEDLINE or PubMed.

Of the 22 abstracts, one10 was a case reportthat also was included in the sample used in alater study by Vlaskalic and Boyd.6 Two otherstudies11,12 of Invisalign were published; one waspublished as an abstract12 and the other was astudy based on that abstract.11 Finally, we deter-mined that only two studies6,11 satisfied the inclu-sion criteria (clinical trials in humans and evalu-ation of Invisalign treatment effects) (Table 2,page 1727). The figure (page 1728) is the flow diagram of the literature search.

Study 1. Vlaskalic and Boyd’s study6 reportedresults obtained on 38 patients (initial intended-to-treat sample of 40; dropout rate of 5 percent).The study’s inclusion criteria were as follows:fully erupted permanent dentition not includingthird molars, dental health without immediateneed for restorations, availability for eveningappointments and a desire to comply with ortho-dontic treatment. The subjects’ age range was 14to 52 years, and some of them had been treatedpreviously with fixed appliances. A $200 incentivewas offered to subjects, as well as a warranty thatthey would undergo a full fixed orthodontic treat-ment if they were not pleased with the results ofthe Invisalign treatment.

Patients with a Class I occlusion with mildcrowding or spacing required an average of 20months’ treatment time. Nine of 10 patients (90




percent) completed their treatment. Severalaligners made from different materials and of dif-ferent thicknesses were used, and several newimpressions were required in the process. At least10 days were required for every aligner, and over-correction of tooth positions was necessary. Theonly reported side effect was posterior open bitecreation, though no specific incidence rates werereported.6

For subjects with a Class I occlusion, with mod-erate crowding, posterior crossbite and linguallyimpacted mandibular premolars, or subjects witha Class III occlusion, with mild to moderatecrowding and anterior crossbite, an average of 27months of treatment time was required. Only 10patients of the 15 in this group (66.7 percent)completed their treatment. These types of casesrequired the addition of specific composite attach-ments to correct rotations, to extrude or rotateteeth and to obtain bodily movements. Theauthors suggested making an impression of thedentition before the removal of any tooth for thevirtual set up.6

For subjects with Class I and Class II division1 occlusion with severe crowding or class II divi-sion 2 occlusion with moderate crowding, anaverage of 32 months of treatment time wasrequired. Only eight patients of the 13 in thesegroups (61.5 percent) completed their treatment.

These types of casesrequired long verticalattachments to main-tain adequate root con-trol in extraction caseswith overcorrection inthe virtual setup.6

As part of a survey,100 percent of the sub-jects claimed that theywould use Invisalignover fixed appliancesand that oral hygienewas easy to maintain.Caries occurred in 5percent of the totalsample.6

Study 2. The studyby Bollen and col-leagues11 was a clinicaltrial evaluating theeffect of activation timeand material stiffnessin the ability to com-

plete use of a first set of prescribed aligners. Atotal of 51 subjects (mean age 34 years, range 19to 55 years; 36 women and 15 men) were assignedrandomly to a hard or soft appliance and a one-week or two-week activation time. Criteria forsubjects’ inclusion in the study were as follows:age older than 18 years, availability to attend theappointments and ability to pay for the services.Baseline characteristics were similar among thefour groups. Only 15 subjects completed the fullset of aligners (a dropout rate of 71 percent). Rea-sons the researchers offered as to why subjects didnot complete the treatment were poor fit as judgedby project orthodontists (23), refusal to proceed tothe next appliance (three) or recommendation byAlign Technology orthodontists to restart theprocess (10). The proportion of subjects who com-pleted the treatment was similar in the fourgroups. The researchers found that the two-weekinterval was more likely to lead to completion ofthe treatment but that the stiffness of the alignerswas not. They also found that more complex caseswere less likely to be completed than were simplercases, and subjects with premolar extractions hadthe largest rate of failure to complete treatment.All of the patients required a second set ofaligners or fixed appliances to complete their ini-tial treatment goals.

Summary. After reviewing both articles, we

TABLE 1

SEARCH RESULTS FROM DIFFERENT INTERNET-ACCESSIBLE DATABASES.

DATABASE

PubMed

MEDLINE

MEDLINE In-Process & Other Non-Indexed Citations

EMBASE (Excerpta Medica)

All Evidence Based MedicineReviews Database (CochraneDatabase of SystematicReviews, American College ofPhysicians Journal Club, Data-base of Abstracts of Reviews of Effects and Cochrane CentralRegister of Controlled Trials)

Thomsen’s ISI Web of Science

LILACS

Invisalign(Align Technology, SantaClara, Calif.)

Invisalign

Invisalign

Invisalign

Invisalign

TS = (Invisalign)

Invisalign

21

21

0

1

2

7

0

0

Not Applicable

0

0

1

0

0

KEY WORD RESULTS ABSTRACTS NOTLISTED ON MEDLINE




determined that neither of them quantified thetreatment effects of Invisalign. Both studies eval-uated completion rates of Invisalign treatmentunder different malocclusion characteristics,material stiffness and interval between aligners.These rates were contradictory, ranging between5 and 71 percent of dropout proportions. Random-ization was used in only one of the studies,11 butboth6,11 were published in peer-reviewed journals.

DISCUSSION

Invisalign was developed to be used as an ortho-dontic treatment alternative for adults with aClass I malocclusion with mild-to-moderatecrowding.5 The company’s Web site3 claims thatInvisalign “has been proven effective” and “can be

used to treat a vast majority of adults and adoles-cents,” giving the impression that most of theorthodontic cases can benefit from this tech-nology. However, Joffe2 defined more specificselection criteria: caution should be taken whendealing with malocclusions that have more than 5millimeters of spacing and crowding, skeletalanteroposterior discrepancies of greater than 2mm, centric relation and occlusion discrepancies,teeth rotations of greater than 20 degrees, ante-rior and posterior open bites, teeth extrusion,teeth tipping of greater than 45 degrees, teethwith short clinical crowns and arches missingmultiple teeth. As can be seen from these refer-ences, there is controversy about the complexityof orthodontic cases that can be treated success-

Beers and colleagues21

Bishop and colleagues14

Bollen and colleagues11

Chenin and colleagues15

Christensen4

Clements and colleagues12

Ellis19

Joffe2

McKenna5

Meier and colleagues1

Miller and colleagues23

Miller and colleagues20

Norris and colleagues13

Owen24

Schuster and colleagues26

Sheridan27

Turpin25

Vlaskalic and Boyd10

Vlaskalic and Boyd6

Wheeler17

Whitehouse18

Wong22

Comment

Case report

Randomized clinical trial

Case report

Comment

Abstract

Letter

Comment

Comment

Prospective survey (patient profiling)

Case report

Validation study

Case report

Case report

In vitro (Invisalign, Align Technology,Santa Clara, Calif, tray experiment)

Comment

Comment

Case report

Clinical trial

Letter

Comment

Comment

N/A*

2 (females, aged 17 and 34 years)

51 (36 females, 15 males; average age 34years)

2 (both women, aged 41 and 42 years)

N/A

N/A

N/A

N/A

N/A

89 (72 percent women aged 20-29 years; 28 percent men aged 30-39 years)

1 (woman, aged 24 years)

N/A

1 (man, aged 39 years)

1

10 patients (trays only)

N/A

N/A

1 (male, aged 35 years)

38 (aged 14-52 years)

N/A

N/A

N/A

TABLE 2

AUTHOR STUDY TYPE NO. IN SAMPLE

* N/A: Not applicable.

STUDY TYPES AND SAMPLES FROM THE ABSTRACTS IDENTIFIED INTHE LITERATURE SEARCH.


fully with Invisalign. Therefore, a systematicreview of the available evidence that may or maynot support the possible dentoalveolar changes ofthis technology seemed warranted. We hoped togive clinicians a better understanding of theadvantages and disadvantages of the technology.

Concerning the available literature, 18 percentof the published material was case reports.10,13-15

In reviewing these, we found that all the subjectswhose cases were reported were diagnosed withmalocclusions not surpassing Joffe’s2 treatmentcriteria and were reported as having been treatedsuccessfully with Invisalign. Only two clinicaltrials have been published. The first trial6 was afeasibility study with 38 patients. It had withmethodological limitations concerning patientselection (nonrandomized and limited sample sizeper group). The researchers also failed to reportprecise malocclusion characteristics with respectto the amount of crowding and other parameters.Nevertheless, they concluded that patients whosepermanent dentition has mild-to-moderate maloc-clusions may benefit from this treatment. Theyalso suggested that prospective, controlled clinicaltrials with adequate sample sizes, increasedrecord base and the use of objective assessmentmethods such as occlusal indexes should be used



to evaluate outcomeswith Invisalign.

The other clinical trialonly reported resultsfrom an initial alignmentphase of treatment withrespect to using differentactivation times andmaterial stiffness.11 Thisgood-quality exploratoryreport followed most ofthe requirements of theConsolidated Standardsof Reporting Trials(CONSORT) statement.16

Although the sample of51 subjects was catego-rized based on theirocclusal characteristics(score on the PeerAssessment Rating[PAR] index), no quantifi-cation of the final treat-ment results after theuse of the initial set ofaligners was reported.

Future reports are expected regarding the magni-tude of the achievement of treatment goals forocclusal change. A two-week activation regimen,no extractions and a low score on the PAR indexwere considered characteristics that increased thechances to complete a course of treatment with aninitial set of aligners. All of these patients under-went a second set of aligners or comprehensiveorthodontic treatment after completing treatmentwith these initial series of aligners.

On the basis of the limitations of the twostudies we evaluated,6,11 we could come to no con-clusions regarding Invisalign treatment effects or,consequently, the system’s treatment indications.Based on these two clinical trials, we can onlyconclude that stiffness of the material does notseem to affect the outcome, a two-week activationperiod seems to be more efficient and complexityof the malocclusion influences the chances to com-plete a set of aligners. Wheeler17 commented thatmany orthodontic products are sent to the marketwithout undergoing sufficient clinical trials,increasing the possibility for practitioners andpatients to be frustrated by the outcomes. Consid-ering this, it is clear that there is a need todevelop well-designed clinical trials of Invisalign’streatment possibilities and limitations. So far, the

Manual search0 papers

Electronic search22 abstracts

Excluded10 papers

(descriptive/letters)

Excluded6 papers

(case reports)

Selection criteria applies to12 papers

Potentially appropriateto be included

6 papers

Excluded1 paper (not clinical trials)

Excluded1 paper (repetition of study)

Potentially appropriateto be included

0 papers

6 papers

3 papers

Finally selected2 papers

Figure. Flow diagram of the literature search.




establishment of most of the indications has beendetermined by the personal experience of the clin-icians using Invisalign. Research on Invisalign isreported to be conducted in diverse locations inthe United States and Europe.2 It is hoped thatthese studies will give us more sound evidenceabout Invisalign’s treatment effects and indications.

A limitation that we can foresee is thatInvisalign appliances used in future studies maynot be the same. Invisalign aligners continue toevolve, including in terms of new material charac-teristics. This would make comparisons betweenfuture studies difficult.

Another important consideration is that mostof the published reports about Invisalign are casereports, which are of interest for clinicians but donot present significant evidence to support treat-ments based on evidence. Also, reports thatappear in non–peer-reviewed journals do notallow for the evaluation of the quantity andquality of the reported data by experts beforebeen exposed to the public.

Because scientific evidence alone should notautomatically dictate the selection of the treat-ment by the health professional, those makinghealth care decisions should consider the valuesof not only the health care professional but alsothe patient. All these factors should be evaluatedto determine whether the intervention benefitsare worth the associated costs.8

CONCLUSIONS

We could make no conclusion from this system-atic review about the indications for, limitationsof and outcomes of use of the Invisalign systembecause we found no study that quantified treat-ment effects or accomplishment of treatmentgoals using it.

Randomized clinical trials that follow theCONSORT statement are needed to evaluate thetreatment effects of Invisalign.

No treatment indications for or limitations ofInvisalign are supported with scientific evidence.Therefore, clinicians will have to rely on theirclinical experience, the opinion of experts and thepresented limited evidence when using Invisalignappliances. ■

Dr. Lagravère is a doctoral student, Orthodontic Graduate Program,Faculty of Medicine and Dentistry, Room 4048, Dentistry/PharmacyCentre, University of Alberta, Edmonton, Alberta, Canada T6G 2N8, e-mail “[email protected]”. Address reprint requests to Dr.Lagravère.

Dr. Flores-Mir is a clinical associate professor and the director, Cran-iofacial and Oral-health Evidence-based Practice Group, OrthodonticGraduate Program, Faculty of Medicine and Dentistry, University ofAlberta, Canada.

The authors offer special thanks to Linda Seale for her assistance inthe database search.

1. Meier B, Wiemer KB, Miethke RR. Invisalign: patient profiling—analysis of a prospective survey. J Orofac Orthop 2003;64(5):352-8.

2. Joffe L. Invisalign: early experiences. J Orthod 2003;30:348-52.3. Align Technology. Invisalign (home page). Available at: “www.

invisalign.com/generalapp/us/en/index.jsp”. Accessed Oct. 28, 2005. 4. Christensen GJ. Orthodontics and the general practitioner. Am J

Orthod Dentofacial Orthop 2002;122:13A. 5. McKenna S. Invisalign: technology or mythology? J Mass Dent Soc

2001;50(2):8-9.6. Vlaskalic V, Boyd RL. Clinical evolution of the Invisalign appli-

ance. J Calif Dent Assoc 2002;30:769-76.7. Dawes M. Evidence-based practice. In: Dawes M, Davies P, Gray

A, Mant J, Seers K, Snowball R, eds. Evidence-based practice: A primerfor health care professionals. London: Churchill Livingstone; 2000:1-8.

8. Guyatt G, Haynes B, Jaeschke R, et al. Introduction: the philos-ophy of evidence-based medicine. In: Guyatt G, Rennie D, eds. Users’guides to the medical literature: A manual for evidence-based practice.Chicago: AMA Press; 2002:3-12.

9. Egger M, Davey Smith G, Altman DG. Systematic reviews inhealth care: Meta-analysis in context. London: BMJ Books; 2001.

10. Vlaskalic V, Boyd R. Orthodontic treatment of a mildly crowdedmalocclusion using the Invisalign System. Aust Orthod J 2001;17(1):41-6.

11. Bollen AM, Huang G, King G, Hujoel P, Ma T. Activation timeand material stiffness of sequential removable orthodontic appliances,part 1: ability to complete treatment. Am J Orthod Dentofacial Orthop2003;124:496-501.

12. Clements KM, Bollen AM, Huang GJ, et al. Randomized trial onfrequency of activation and stiffness of Invisalign appliances (abstract2917). J Dent Res 2003;82(special issue B June):B-374.

13. Norris RA, Brandt DJ, Crawford CH, Fallah M. Restorative andInvisalign: a new approach. J Esthet Restor Dent 2002;14:217-24.

14. Bishop A, Womack WR, Derakhshan M. An esthetic and remov-able orthodontic treatment option for patients: Invisalign. Dent Assist2002;71(5):14-7.

15. Chenin DA, Trosien AH, Fong PF, Miller RA, Lee RS. Orthodontictreatment with a series of removable appliances. JADA 2003;134:1232-9. (Erratum appears in JADA 2003;134:1322.)

16. Moher D, Schulz KF, Altman DG, for the CONSORT (Consoli-dated Standards of Reporting Trials) Group. Revised recommendationsfor improving the quality of reports of parallel group randomized trials2001. Available at: “www.consort-statement.org/Statement/revisedstatement.htm#app”. Accessed Oct. 28, 2005.

17. Wheeler TT. Invisalign material studies. Am J Orthod Dentofa-cial Orthop 2004;125(3):19A.

18. Whitehouse JA. Everyday uses of adult orthodontics. Dent Today2004;23(9):116, 118, 120.

19. Ellis CP. Invisalign and changing relationships. Am J OrthodDentofacial Orthop 2004;126(1):20A-21A.

20. Miller RJ, Kuo E, Choi W. Validation of Align Technology’s TreatIII digital model superimposition tool and its case application. OrthodCraniofac Res 2003;6(supplement 1):143-9.

21. Beers AC, Choi W, Pavlovskaia E. Computer-assisted treatmentplanning and analysis. Orthod Craniofac Res 2003;6(supplement1):117-25.

22. Wong BH. Invisalign A to Z. Am J Orthod Dentofacial Orthop2002;121(5):540-1.

23. Miller RJ, Duong TT, Derakhshan M. Lower incisor extractiontreatment with the Invisalign system. J Clin Orthod 2002;36(2):95-102.

24. Owen AH 3rd. Accelerated Invisalign treatment. J Clin Orthod2001;35:381-5.

25. Turpin DL. Clinical trials needed to answer questions aboutInvisalign. Am J Orthod Dentofacial Orthop 2005;127(2):157-8.

26. Schuster S, Eliades G, Zinelis S, Eliades T, Bradley TG. Struc-tural conformation and leaching from in vitro aged and retrievedInvisalign appliances. Am J Orthod Dentofacial Orthop 2004;126:725-8.

27. Sheridan JJ. What percentage of your patients are being treatedwith Invisalign appliances? J Clin Orthod 2004;38:544-5.


Documents

The Treatment Effects Of Invisalign Orthodontic Aligners