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Evidence-Based Dentistry and the Absence of Evidence From Randomized Controlled Trials for Common Dental Procedures
COMMENTARY Evidence-Based Dentistry and the Absence of Evidence From Randomized Controlled Trials for Common Dental Procedures By Thomas Dietrich, DMD, MD, MPH
This year, the American Dental Association Foundation will provide $100,000 in funding for systematic literature reviews addressing 4 high-priority clinical questions as identified by an American Dental Association workshop on evidence-based dentistry1: 1. At what frequency is dental prophylaxis effective in preventing periodontitis in individuals with and without known risk factors? 2. Does correcting malocclusion in children and adults reduce the risk of periodontal disease? 3. What are the clinical, biological, psychosocial and/or economic outcomes of treating a pulpally involved (periodontally sound) single tooth through: endodontic care, extraction and implant placement, fixed partial denture and/or extraction without implant placement? 4. What are the longitudinal beneficial and harmful effects of endodontic services compared to extraction and implant placement? It is interesting to note that all these questions are dealing with key long-term outcomes of dental procedures as currently administered on a routine basis in dental practice. This illustrates the tremendous degree of uncertainty among the profession with regard to the risks and benefits of basic dental procedures that have been major elements of dental care for decades. In the era of evidence-based dentistry, what kind of evidence would we want to see for the above dental procedures? I will use the first clinical question as an example; however, many issues discussed below are equally relevant to all other clinical questions. The Evidence-Based Medicine Levels of Evidence2 indicate that the highest achievable level of evidence (level Ia) is represented by a systematic review of randomized controlled trials (RCTs) with homogeneity of effects. In other words, several individual RCTs in different study populations would have to have found very
192 Dental Abstracts
similar results as to what frequency of dental prophylaxis works best to prevent periodontitis. The second highest level of evidence (level Ib) would be achieved by an individual RCT with narrow confidence intervals (ie, an RCT with a large sample size).
“Well-designed observational studies may be a viable, cost-efficient alternative” As RCTs are considered to provide ultimate proof for the efficacy and effectiveness of preventive measures, one can frequently find systematic reviews restricted to RCTs (ie, other nonrandomized study designs are excluded a priori).3-5 Typically, these reviews include very few RCTs, the main implication being a call for high-quality RCTs to be conducted.3-5 The notion that RCTs are needed to prove an effect occasionally leads authors to call for RCTs, even for research questions that cannot be addressed by RCTs.6 For example, one cannot possibly conduct an RCT to evaluate the predictive value of bleeding on probing as indicators for risk of future attachment loss, simply because bleeding on probing cannot be randomized to sites or people.6 Although this is not an issue with any intervention, there are other reasons for which RCTs may not be feasible, including ethical reasons and a missed window of opportunity. A central concept underlying both these issues is the concept of clinical equipoise. Clinical equipoise means a genuine uncertainty on behalf of the expert medical community about the comparative preventive merits of each trial arm. The tenet of clinical equipoise provides a clear moral foundation to the requirement that the health care of subjects not be disadvantaged by research participation. A recent Cochrane review on recall intervals
for the prevention of dental disease, including periodontitis, yielded 1 RCT and concluded that there is insufficient evidence from RCTs for different recall intervals. I would argue that equipoise may be an issue here, as the “expert dental community” may not feel a genuine uncertainty regarding the benefits of more frequent dental prophylaxis. Also, study subjects may be more likely to drop out due to a perception that their periodontal health is being neglected.7 The reason that RCTs rank highest is that, theoretically, they are not susceptible to various biases simply because, with the exception of the study intervention itself, the distribution of all known and unknown characteristics that may affect the outcome under study is identical between the different study groups. Hence, any observed difference in periodontitis risk between study arms can only be attributed to the different frequencies of dental prophylaxis tested. That’s the theory. However, as Yogi Berra stated, “In theory there is no difference between theory and practice. In practice there is.” In practice, RCTs are susceptible to biases, and this is particularly relevant in the context of the important clinical questions discussed here. The 2 major issues here are compliance and dropout (loss to follow-up). In a study on the effects of dental prophylaxis, individuals may be randomized to study groups with different frequencies of dental prophylaxis; however, not all will comply with the regimen to which they were assigned. From experience, practitioners may expect a substantial proportion of noncompliers in such a study. The problem is that noncompliance cannot be randomized, that is, it is selfselected and may be associated with other determinants of periodontitis risk, thereby introducing bias. The assessment of meaningful periodontitis end points requires long-term follow-up, and high drop-out rates may pose an even more significant problem. A recent systematic review of studies on the effect of professional mechanical plaque removal on prevention of periodontitis identified 5 RCTs with a follow-up period of at least 2 years.8 Dropout rates in these studies varied between 8% and 56%. Again, the problem is that dropouts cannot be randomized and may thus introduce bias. In fact, RCTs with more than 20% dropout are considered “low quality” RCTs and assigned an evidence level of IIb.2 Dropouts and compliance
may be particularly problematic in studies on the primary prevention of periodontitis simply because very long follow-up periods are necessary to record a sufficient number of incident periodontitis cases. In conclusion, the conduct of high-quality RCTs may not be a realistic goal for many dental interventions and procedures. Well-designed observational studies may be a viable, cost-efficient alternative. For specific clinical questions, such as the effectiveness of different frequencies of dental prophylaxis for the primary prevention of periodontitis, observational studies such as cohort or case-control studies may be the only realistic option.
References 1. Request for Proposals: Systematic Review to Support EvidenceBased Dentistry and Dental Research. ADA Foundation 2006: http://ada.org/ada/prod/adaf/prog_research_rfp.asp (last accessed: 02/17/06). 2. Levels of Evidence and Grades of Recommendation. OxfordCentre for Evidence Based Medicine 2001: http://www.cebm.net /levels of evidence.asp (last accessed: 02/15/06). 3. Beirne P, Forgie A, Worthington HV, et al: Routine scale and polish for periodontal health in adults. Cochrane Database of Systematic Reviews 4:2005. 4. Beirne P, Forgie A, Clarkson JE, et al: Recall intervals for oral health in primary care patients. Cochrane Database of Systematic Reviews 4:2005. 5. Hujoel PP, Cunha-Cruz J, Loesche WJ, et al: Personal oral hygiene and chronic periodontitis: A systematic review. Periodontol 2000 37:29-34, 2005. 6. Renvert S, Persson GR: A systematic review on the use of residual probing depth, bleeding on probing and furcation status following initial periodontal therapy to predict further attachment and tooth loss. J Clin Periodontol 29:82-89; discussion 9091, 2002. 7. Listgarten MA, Sullivan P, George C, et al: Comparative longitudinal study of 2 methods of scheduling maintenance visits: 4year data. J Clin Periodontol 16:105-115, 1989. 8. Needleman I, Suvan J, Moles DR, et al: A systematic review of professional plaque removal for prevention of periodontal diseases. J Clin Periodontol 32:229-282, 2005.
Thomas Dietrich is Assistant Professor, Department of Health Policy and Health Services Research, Department of Periodontology and Oral Biology, Boston University, Boston, Massachusetts.
Volume 51 • Issue 4 • 2006 193
This year, the American Dental Association Foundation will provide $100,000 in funding for systematic literature reviews addressing 4 high-priority clinical questions as identified by an American Dental Association workshop on evidence-based dentistry1: 1. At what frequency is dental prophylaxis effective in preventing periodontitis in individuals with and without known risk factors? 2. Does correcting malocclusion in children and adults reduce the risk of periodontal disease? 3. What are the clinical, biological, psychosocial and/or economic outcomes of treating a pulpally involved (periodontally sound) single tooth through: endodontic care, extraction and implant placement, fixed partial denture and/or extraction without implant placement? 4. What are the longitudinal beneficial and harmful effects of endodontic services compared to extraction and implant placement? It is interesting to note that all these questions are dealing with key long-term outcomes of dental procedures as currently administered on a routine basis in dental practice. This illustrates the tremendous degree of uncertainty among the profession with regard to the risks and benefits of basic dental procedures that have been major elements of dental care for decades. In the era of evidence-based dentistry, what kind of evidence would we want to see for the above dental procedures? I will use the first clinical question as an example; however, many issues discussed below are equally relevant to all other clinical questions. The Evidence-Based Medicine Levels of Evidence2 indicate that the highest achievable level of evidence (level Ia) is represented by a systematic review of randomized controlled trials (RCTs) with homogeneity of effects. In other words, several individual RCTs in different study populations would have to have found very
192 Dental Abstracts
similar results as to what frequency of dental prophylaxis works best to prevent periodontitis. The second highest level of evidence (level Ib) would be achieved by an individual RCT with narrow confidence intervals (ie, an RCT with a large sample size).
“Well-designed observational studies may be a viable, cost-efficient alternative” As RCTs are considered to provide ultimate proof for the efficacy and effectiveness of preventive measures, one can frequently find systematic reviews restricted to RCTs (ie, other nonrandomized study designs are excluded a priori).3-5 Typically, these reviews include very few RCTs, the main implication being a call for high-quality RCTs to be conducted.3-5 The notion that RCTs are needed to prove an effect occasionally leads authors to call for RCTs, even for research questions that cannot be addressed by RCTs.6 For example, one cannot possibly conduct an RCT to evaluate the predictive value of bleeding on probing as indicators for risk of future attachment loss, simply because bleeding on probing cannot be randomized to sites or people.6 Although this is not an issue with any intervention, there are other reasons for which RCTs may not be feasible, including ethical reasons and a missed window of opportunity. A central concept underlying both these issues is the concept of clinical equipoise. Clinical equipoise means a genuine uncertainty on behalf of the expert medical community about the comparative preventive merits of each trial arm. The tenet of clinical equipoise provides a clear moral foundation to the requirement that the health care of subjects not be disadvantaged by research participation. A recent Cochrane review on recall intervals
for the prevention of dental disease, including periodontitis, yielded 1 RCT and concluded that there is insufficient evidence from RCTs for different recall intervals. I would argue that equipoise may be an issue here, as the “expert dental community” may not feel a genuine uncertainty regarding the benefits of more frequent dental prophylaxis. Also, study subjects may be more likely to drop out due to a perception that their periodontal health is being neglected.7 The reason that RCTs rank highest is that, theoretically, they are not susceptible to various biases simply because, with the exception of the study intervention itself, the distribution of all known and unknown characteristics that may affect the outcome under study is identical between the different study groups. Hence, any observed difference in periodontitis risk between study arms can only be attributed to the different frequencies of dental prophylaxis tested. That’s the theory. However, as Yogi Berra stated, “In theory there is no difference between theory and practice. In practice there is.” In practice, RCTs are susceptible to biases, and this is particularly relevant in the context of the important clinical questions discussed here. The 2 major issues here are compliance and dropout (loss to follow-up). In a study on the effects of dental prophylaxis, individuals may be randomized to study groups with different frequencies of dental prophylaxis; however, not all will comply with the regimen to which they were assigned. From experience, practitioners may expect a substantial proportion of noncompliers in such a study. The problem is that noncompliance cannot be randomized, that is, it is selfselected and may be associated with other determinants of periodontitis risk, thereby introducing bias. The assessment of meaningful periodontitis end points requires long-term follow-up, and high drop-out rates may pose an even more significant problem. A recent systematic review of studies on the effect of professional mechanical plaque removal on prevention of periodontitis identified 5 RCTs with a follow-up period of at least 2 years.8 Dropout rates in these studies varied between 8% and 56%. Again, the problem is that dropouts cannot be randomized and may thus introduce bias. In fact, RCTs with more than 20% dropout are considered “low quality” RCTs and assigned an evidence level of IIb.2 Dropouts and compliance
may be particularly problematic in studies on the primary prevention of periodontitis simply because very long follow-up periods are necessary to record a sufficient number of incident periodontitis cases. In conclusion, the conduct of high-quality RCTs may not be a realistic goal for many dental interventions and procedures. Well-designed observational studies may be a viable, cost-efficient alternative. For specific clinical questions, such as the effectiveness of different frequencies of dental prophylaxis for the primary prevention of periodontitis, observational studies such as cohort or case-control studies may be the only realistic option.
References 1. Request for Proposals: Systematic Review to Support EvidenceBased Dentistry and Dental Research. ADA Foundation 2006: http://ada.org/ada/prod/adaf/prog_research_rfp.asp (last accessed: 02/17/06). 2. Levels of Evidence and Grades of Recommendation. OxfordCentre for Evidence Based Medicine 2001: http://www.cebm.net /levels of evidence.asp (last accessed: 02/15/06). 3. Beirne P, Forgie A, Worthington HV, et al: Routine scale and polish for periodontal health in adults. Cochrane Database of Systematic Reviews 4:2005. 4. Beirne P, Forgie A, Clarkson JE, et al: Recall intervals for oral health in primary care patients. Cochrane Database of Systematic Reviews 4:2005. 5. Hujoel PP, Cunha-Cruz J, Loesche WJ, et al: Personal oral hygiene and chronic periodontitis: A systematic review. Periodontol 2000 37:29-34, 2005. 6. Renvert S, Persson GR: A systematic review on the use of residual probing depth, bleeding on probing and furcation status following initial periodontal therapy to predict further attachment and tooth loss. J Clin Periodontol 29:82-89; discussion 9091, 2002. 7. Listgarten MA, Sullivan P, George C, et al: Comparative longitudinal study of 2 methods of scheduling maintenance visits: 4year data. J Clin Periodontol 16:105-115, 1989. 8. Needleman I, Suvan J, Moles DR, et al: A systematic review of professional plaque removal for prevention of periodontal diseases. J Clin Periodontol 32:229-282, 2005.
Thomas Dietrich is Assistant Professor, Department of Health Policy and Health Services Research, Department of Periodontology and Oral Biology, Boston University, Boston, Massachusetts.
Volume 51 • Issue 4 • 2006 193