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The need to register clinical trials in orthodontics
EDITORIAL
The need to register clinical trials in orthodontics David L. Turpin, Editor-in-Chief Seattle, Wash
W
hile attending a meeting of the College of Diplomates of the American Board of Orthodontics, I was impressed with the thirst for additional evidence supporting traditional orthodontic care. Time and time again, I was asked where clinicians could become current with the literature, especially when meta-analyses, systematic reviews, and controlled clinical trials are published to answer clinical questions with some authority. Of great help is a new American Association of Orthodontists’ online resource that is updated monthly by our librarian, Jackie Hittner, with support from the Council on Scientific Affairs. To use this clearinghouse of information, log in to www.AAOmembers. org. Select the “Library and Research” link and then the “Evidence-based Orthodontic Research” link. The Council on Scientific Affairs conducts periodic searches, reviews the search results, and posts all systematic reviews, meta-analyses, practice guidelines, and summary statements that are related to orthodontics. At last count, the site listed over 50 reviews. But what about the researcher planning to start a clinical trial or the person who wants information about trials currently underway? Is there a place where the protocol for a specific clinical trial is listed while the sample is being recruited? The answer is yes, and a quick look at the National Institutes of Health website may be of interest to you. A statement from the International Committee of Medical Journal Editors (http://www.icmje.org/clin_ trialup.htm)1 summarizes why the registration of prospective clinical trials is so important. “A complete registry of trials would be a fitting way to thank the thousands of participants who have placed themselves at risk by volunteering for clinical trials. They deserve to know that the information that accrues from their altruism is part of the public record, where it is available to guide decisions about patient care, and deserve to know that decisions about their care rest on all of the evidence, not just the trials that authors decided to report and that
Am J Orthod Dentofacial Orthop 2006;130:429-30 0889-5406/$32.00 Copyright © 2006 by the American Association of Orthodontists. doi:10.1016/j.ajodo.2006.08.009
journal editors decided to publish.” The time has come for registration to become the standard, and, around the world, governments are beginning to legislate mandatory disclosure of all trials. There are other reasons to register trials. It might prevent redundancy in certain research topics and assist in allowing subsequent investigators to gather data similarly so that pooling or comparison of the results can be more easily accomplished. With the publication of this editorial, the AJO-DO is adopting a policy that requires registration before the findings of a clinical trial are accepted for publication. The database for registration is held by the National Institutes of Health (http://prsinfo.clinicaltrials.gov), and the service is free to investigators. The important point is that a trial should be registered before any patients are recruited. This is usually immediately after approval by the appropriate ethics committee. I went to the site recently, searched on “ORTHODONTICS,” and found protocols for 2 trials. The first is a proposed study of the efficacy of Elmex gel in preventing white-spot lesions by Meir Redlich, Hadassah Medical Organization, Jerusalem, Israel. The second trial aims to distinguish subjects who react in a favorable way to the correction of Class II malocclusion with a functional appliance. Effie Basdra is the principal investigator for this proposed study at Aristotle University of Thessaloniki, Greece. Using the search term, “ORTHODONTIC TREATMENT,” I found 6 proposed studies, ranging from early treatment to the use of mini-screws for anchorage, with all still in the recruiting-patients phase. With this change, authors must thoroughly understand the requirements of registration. The accepted definition of a clinical trial includes, “Any research project that prospectively assigns human subjects to intervention and comparison groups to study the causeand-effect relationship between a medical/dental intervention and a health outcome.” Attendees at a meeting of the World Health Organization registration advisory group identified a minimal registration data set of 20 items (Table) that have served related organizations well. Data entries include information that will be of 429
430 Editorial
Table.
American Journal of Orthodontics and Dentofacial Orthopedics October 2006
Minimal registration data set
Item
Comment
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
The unique trial number will be established by the primary registering entity (the registry). The date of registration will be established by the primary registering entity. May be assigned by sponsors or other interested parties (there may be none). Name of the organization(s) that provided funding for the study. The main entity responsible for performing the research. The secondary entities, if any, responsible for performing the research. Public contact person for the trial, for patients interested in participating. Person to contact for scientific inquiries about the trial. Brief title chosen by the research group (can be omitted if the researchers wish). This title must include the name of the study intervention, the condition being studied, and the outcome (eg, The International Study of Digoxin and Death from Congestive Heart Failure). Has the study at the time of registration received appropriate ethics committee approval (yes/no)? (It is assumed that all registered trials will be approved by an ethics board before commencing.) The medical condition being studied (eg, asthma, myocardial infarction, depression). A description of the study and comparison/control intervention(s). Key patient characteristics that determine criteria eligibility for participation in the study. Database should provide drop-down lists for selection. This would include choices for randomized vs nonrandomized, etc. Estimated enrollment date of the first participant. The total number of subjects the investigators plan to enroll before closing the trial to new participants. Is this information available (yes/no)? (If yes, link to information.) The primary outcome that the study was designed to evaluate. Description should include the time at which the outcome is measured (eg, blood pressure at 12 months). The secondary outcomes specified in the protocol. Description should include time of measurement (eg, creatinine clearance at 6 months).
Unique trial number Trial registration date Secondary IDs Funding source(s) Primary sponsor Secondary sponsor(s) Responsible contact person Research contact person Title of the study Official scientific title
11. Research ethics review 12. 13. 14. 15.
Condition Intervention(s) Inclusion and exclusion Study type
16. 17. 18. 19.
Anticipated trial start date Target sample size Recruitment status Primary outcome
20. Key secondary outcomes
value to patients and health professionals when searched by members of the research community. The registry must be electronically searchable and accessible to the public at no charge. It must be open to all registrants and not for profit. In general, the purpose of a clinical-trial registry is to promote the public good by ensuring that everyone can find key information about every clinical trial in the world whose principal aim is to shape medical and dental decision making.
The editors of the AJO-DO are committed to do whatever we can to help reach this goal. To this end, every trial participant and every investigator should ask, “Is this clinical trial fully registered?” REFERENCE 1. De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. Ann Intern Med 2004;141: 477-8. Epub 2004 Sep 8. [PMID: 15355883]
The need to register clinical trials in orthodontics David L. Turpin, Editor-in-Chief Seattle, Wash
W
hile attending a meeting of the College of Diplomates of the American Board of Orthodontics, I was impressed with the thirst for additional evidence supporting traditional orthodontic care. Time and time again, I was asked where clinicians could become current with the literature, especially when meta-analyses, systematic reviews, and controlled clinical trials are published to answer clinical questions with some authority. Of great help is a new American Association of Orthodontists’ online resource that is updated monthly by our librarian, Jackie Hittner, with support from the Council on Scientific Affairs. To use this clearinghouse of information, log in to www.AAOmembers. org. Select the “Library and Research” link and then the “Evidence-based Orthodontic Research” link. The Council on Scientific Affairs conducts periodic searches, reviews the search results, and posts all systematic reviews, meta-analyses, practice guidelines, and summary statements that are related to orthodontics. At last count, the site listed over 50 reviews. But what about the researcher planning to start a clinical trial or the person who wants information about trials currently underway? Is there a place where the protocol for a specific clinical trial is listed while the sample is being recruited? The answer is yes, and a quick look at the National Institutes of Health website may be of interest to you. A statement from the International Committee of Medical Journal Editors (http://www.icmje.org/clin_ trialup.htm)1 summarizes why the registration of prospective clinical trials is so important. “A complete registry of trials would be a fitting way to thank the thousands of participants who have placed themselves at risk by volunteering for clinical trials. They deserve to know that the information that accrues from their altruism is part of the public record, where it is available to guide decisions about patient care, and deserve to know that decisions about their care rest on all of the evidence, not just the trials that authors decided to report and that
Am J Orthod Dentofacial Orthop 2006;130:429-30 0889-5406/$32.00 Copyright © 2006 by the American Association of Orthodontists. doi:10.1016/j.ajodo.2006.08.009
journal editors decided to publish.” The time has come for registration to become the standard, and, around the world, governments are beginning to legislate mandatory disclosure of all trials. There are other reasons to register trials. It might prevent redundancy in certain research topics and assist in allowing subsequent investigators to gather data similarly so that pooling or comparison of the results can be more easily accomplished. With the publication of this editorial, the AJO-DO is adopting a policy that requires registration before the findings of a clinical trial are accepted for publication. The database for registration is held by the National Institutes of Health (http://prsinfo.clinicaltrials.gov), and the service is free to investigators. The important point is that a trial should be registered before any patients are recruited. This is usually immediately after approval by the appropriate ethics committee. I went to the site recently, searched on “ORTHODONTICS,” and found protocols for 2 trials. The first is a proposed study of the efficacy of Elmex gel in preventing white-spot lesions by Meir Redlich, Hadassah Medical Organization, Jerusalem, Israel. The second trial aims to distinguish subjects who react in a favorable way to the correction of Class II malocclusion with a functional appliance. Effie Basdra is the principal investigator for this proposed study at Aristotle University of Thessaloniki, Greece. Using the search term, “ORTHODONTIC TREATMENT,” I found 6 proposed studies, ranging from early treatment to the use of mini-screws for anchorage, with all still in the recruiting-patients phase. With this change, authors must thoroughly understand the requirements of registration. The accepted definition of a clinical trial includes, “Any research project that prospectively assigns human subjects to intervention and comparison groups to study the causeand-effect relationship between a medical/dental intervention and a health outcome.” Attendees at a meeting of the World Health Organization registration advisory group identified a minimal registration data set of 20 items (Table) that have served related organizations well. Data entries include information that will be of 429
430 Editorial
Table.
American Journal of Orthodontics and Dentofacial Orthopedics October 2006
Minimal registration data set
Item
Comment
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
The unique trial number will be established by the primary registering entity (the registry). The date of registration will be established by the primary registering entity. May be assigned by sponsors or other interested parties (there may be none). Name of the organization(s) that provided funding for the study. The main entity responsible for performing the research. The secondary entities, if any, responsible for performing the research. Public contact person for the trial, for patients interested in participating. Person to contact for scientific inquiries about the trial. Brief title chosen by the research group (can be omitted if the researchers wish). This title must include the name of the study intervention, the condition being studied, and the outcome (eg, The International Study of Digoxin and Death from Congestive Heart Failure). Has the study at the time of registration received appropriate ethics committee approval (yes/no)? (It is assumed that all registered trials will be approved by an ethics board before commencing.) The medical condition being studied (eg, asthma, myocardial infarction, depression). A description of the study and comparison/control intervention(s). Key patient characteristics that determine criteria eligibility for participation in the study. Database should provide drop-down lists for selection. This would include choices for randomized vs nonrandomized, etc. Estimated enrollment date of the first participant. The total number of subjects the investigators plan to enroll before closing the trial to new participants. Is this information available (yes/no)? (If yes, link to information.) The primary outcome that the study was designed to evaluate. Description should include the time at which the outcome is measured (eg, blood pressure at 12 months). The secondary outcomes specified in the protocol. Description should include time of measurement (eg, creatinine clearance at 6 months).
Unique trial number Trial registration date Secondary IDs Funding source(s) Primary sponsor Secondary sponsor(s) Responsible contact person Research contact person Title of the study Official scientific title
11. Research ethics review 12. 13. 14. 15.
Condition Intervention(s) Inclusion and exclusion Study type
16. 17. 18. 19.
Anticipated trial start date Target sample size Recruitment status Primary outcome
20. Key secondary outcomes
value to patients and health professionals when searched by members of the research community. The registry must be electronically searchable and accessible to the public at no charge. It must be open to all registrants and not for profit. In general, the purpose of a clinical-trial registry is to promote the public good by ensuring that everyone can find key information about every clinical trial in the world whose principal aim is to shape medical and dental decision making.
The editors of the AJO-DO are committed to do whatever we can to help reach this goal. To this end, every trial participant and every investigator should ask, “Is this clinical trial fully registered?” REFERENCE 1. De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. Ann Intern Med 2004;141: 477-8. Epub 2004 Sep 8. [PMID: 15355883]