The Classic Caries Clinical Trial: Constraints and Opportunities

Amberson JB Jr , McMahon BT , Pinner M (1931). A clinical trial of sanocrysin in pulmonary tuberculosis. Am Rev Tuberc 24: 401–435.

Beacham BE , Kurgansky D , Gould WM (1990). Circumoral dermatitis caused by tartar control dentifrices. J Am Acad Dermatol 22: 1029–1032.

Begg C , Cho M , Eastwood S , Horton R , Moher D , Olkin I (1996). Improving the quality of reporting of randomized controlled trials. J Am Med Assoc 276: 637–639.

Bell RM , Klein SP (1984). Management and evaluation of the effects of misclassification in a controlled clinical trial. J Dent Res 63(Spec Iss):731–734.

Blackwelder WC (1982). ‘Proving the null hypothesis’ in clinical trials. Controlled Clin Trials 3: 345–353.

Blackwelder WC (2001). Equivalence trials. In: Biostatistics in clinical trials. Redmond CK , Colton T , editors. New York: Wiley, pp. 179–185.

Blackwelder WC , Chang MA (1984). Sample size graphs for ‘proving the null hypothesis’. Controlled Clin Trials 5: 97–105.

Brittain E , Wittes J (1989). Factorial designs in clinical trials: the effectiveness of non-compliance and subadditivity. Stat Med 8: 161–171.

Brown BW (1980). The crossover experiment for clinical trials. Biometrics 36: 69–80.

Buck C , Donner A (1982). The design of controlled experiments in the evaluation of non-therapeutic interventions. J Chron Dis 35: 531–538.

Bull JP (1959). The historical development of clinical therapeutic trials. J Chron Dis 10: 218–248.

Caplan DJ , Slade GD , Biesbrock AR , Bartizek RD , McClanahan SF , Beck JD (1999). A comparison of increment and incidence density analyses in evaluating the anticaries effects of two dentrifices. Caries Res 33: 16–22.

CAPS Investigators (1994). The cardiac arrhythmia pilot study. Am J Cardiol 57: 91–95.

Carriere KC (1994). Crossover designs for clinical trials. Stat Med 13: 1063–1069.

Chalmers TC (1993). Meta-analytic stimulus for changes in clinical trials. Stat Methods Med Res 2: 161–172.

Chesters RK , Pitts NB , Matuliene G , Kvedariene A , Huntington E , Bendinskaite R (2002). An abbreviated caries clinical trial design validated over 24 months. J Dent Res 81: 637–640.

Chilton NW , Fertig JW (1958). Clinical dental trial. I. A new caries-inhibitory agent. J Dent Res 37: 335–350.

Chow SC , Liu J (1992). Design and analysis of bioavailability and bioequivalence studies. New York: Marcel Dekker.

CIOMS/WHO (1993). International ethical guidelines for biomedical research involving human subjects. Geneva: CIOMS.

Clark DC , Mechanic M , Banting DW (1982). A further look at the role of radiographs in trials of caries-prophylactic agents. J Pub Health Dent 42: 237–250.

Clark DC , Hanley JA , Weinstein PL , Stamm JW (1985). An empirically based system to estimate the effectiveness of caries preventive agents. Caries Res 19: 83–95.

Cohen J (1994). Clinical trial monitoring: hit or miss? Science 264: 1534–1537.

Cornfield J (1978). Randomization by group: a formal analysis. Am J Epidemiol 108: 100–102.

Council on Dental Therapeutics (1988). Report of workshop aimed at defining guidelines for caries clinical trials: superiority and equivalency claims for anticaries dentifrices. J Am Dent Assoc 117: 663–665.

D'Agostino RB , Massaro JM (2004). New developments in medical clinical trials. J Dent Res 83(Spec Iss C): C18–C24.

Daniels M , Hill AB (1952). Chemotherapy of pulmonary tuberculosis in young adults: an analysis of the combined results of three medical research council trials. Br Med J 1: 1162–1168.

DeLattre VF (1999). Factors contributing to adverse soft tissue reactions due to the use of tartar control toothpastes: report of a case and literature review. J Periodontol 70: 803–807.

DerSimonian R , Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials 7: 177–188.

Donner A , Birkett N , Buck C (1981). Randomization by cluster: sample size requirements and analysis. Am J Epidemiol 114: 906–914.

Downer MC , Worthington HV (1992). The status of bite-wing radiographs in enhancing discriminatory ability in prophylactic clinical trials. Caries Res 26: 195–200.

Egger M , Juni P , Bartlett C (2001). Value of flow diagrams in reports of randomized controlled trials. J Am Med Assoc 285: 1996–1999.

Enas GG , Dornseif BE , Sampson CB , Rockhold FW , Wuu J (1989). Monitoring versus interim analysis of clinical trials: a perspective from the pharmaceutical industry. Cont Clin Trials 10: 57–70.

Ferlito TA (1992). Tartar-control toothpaste and perioral dermatitis. J Clin Orthod 26: 43–44.

Firestone AR , Sema D , Heaven TJ , Weems RA (1998). The effect of a knowledge-based, image analysis and clinical decision support system on observer performance in the diagnosis of approximal caries from radiographic images. Caries Res 32: 127–134.

Fisher RA (1925). Statistical methods for research workers. Edinburgh: Oliver & Boyd.

Fisher RA (1926). The arrangement of field experiments. J Min Agric G Br 33: 503–513.

Fleiss JL (1982). Multicentre clinical trials: Bradford Hill's contributions and some subsequent developments. Stat Med 1: 353–359.

Fleiss J (1984). Assessing treatment effects in caries trials using ordered categorical data. J Dent Res 63(Spec Iss):778–782.

Fleiss J (1986). Analysis of data from multiclinic trials. Control Clin Trials 7: 267–275.

Fleiss JL , Fischman SL , Chilton NW , Park MH (1979). Reliability of discrete measurements in caries trials. Caries Res 13: 23–31.

Freedman B (1987). Equipoise and the ethics of clinical research. N Engl J Med 317: 141–145.

Friedman LM , Furberg CD , DeMets DL (1996). Fundamentals of clinical trials. 3rd ed. St. Louis: Mosby.

Geary DN , Huntington E , Gilbert RJ (1992). Analysis of multivariate data from four dental clinical trials. J R Statist Soc A 155: 77–89.

Gillum RF , Williams PT , Sondike E (1980). Some considerations for the planning of the total community prevention trials—when is sample size adequate? J Community Health 5: 270–278.

Gould L (1998). Multi-centre trial analysis revisited. Stat Med 17: 1779–1797.

Grainger DJ , Lehnoff RW , Bollmer BW , Zacherl WA (1984). Analysis of covariance in dental caries clinical trials. J Dent Res 63(Spec Iss):766–771.

Hannigan A , O'Mullane DM , Barry D , Schafer R , Roberts AJ (2001). A re-analysis of a caries clinical trial by survival analysis. J Dent Res 80: 427–431.

Hannigan A (2004). Using survival methodologies in demonstrating caries efficacy. J Dent Res 83(Spec Iss C): C99–C102.

Heifetz SB (1983). Ethical considerations and study design. Proceedings of the Conference on Caries Clinical Trials.Chicago, IL: American Dental Association.

Hill AB (1952). The clinical trial. N Engl J Med 247: 113–119.

Hujoel PP , Isokangas PJ , Tiekso J , Davis S , Lamont RJ , DeRouen TA (1994). A re-analysis of caries rates in a preventive trial using Poisson regression models. J Dent Res 73: 573–579.

Hunt RJ (1986). Percent agreement, Pearson's correlation, and kappa as measures of inter-examiner reliability. J Dent Res 65: 128–130.

Imrey PB , Kingman A (2004). Analysis of clinical trials involving noncavitated caries lesions. J Dent Res 83(Spec Iss C): C103–C108.

Jadad A (1998). Randomized controlled trials. London: BMJ Books.

James KE , Forrest WH Jr , Rose RL (1985). Crossover and noncrossover designs in four-point parallel line analgesic assays. Clin Pharmacol Ther 37: 242–252.

Johnson MF (1993). Comparative efficacy of NaF and SMFP dentifrices in caries prevention: a meta-analytic overview. Caries Res 27: 328–336.

Johnson MF (2004). The role of risk factors in the identification of appropriate subjects for caries clinical trials: validity and efficiency considerations. J Dent Res 83(Spec Iss C): C116–C118.

Jones B , Jarvis P , Lewis JA , Ebbutt AF (1996). Trials to assess equivalence: the importance of rigorous methods. Br Med J 313: 36–39.

Katz BP , Huntington E (2004). Statistical issues for combining multiple caries diagnostics for demonstrating caries efficacy. J Dent Res 83(Spec Iss C):C109–C112.

Kingman A (1977). Adequate cohort sizes for caries clinical trials. Community Dent Oral Epidemiol 6: 30–35.

Kingman A (1978). A method of utilizing the subjects’ initial caries experience to increase efficiency in caries clinical trials. Biometry Section, National Caries Program. Bethesda, MD: National Institute of Dental Research.

Kingman A (1984). Stratification methods in caries clinical trials. J Dent Res 63(Spec Iss): 773–777.

Kingman A (1992). Specific statistical considerations relevant to the design and analysis of gingivitis trials demonstrating product superiority or equivalence. J Periodontal Res 27: 378–389.

Klein H , Palmer CE , Knutson JW (1938). Studies on dental caries, dental status and dental needs of elementary school children. Pub Health Reports 53: 751–765.

Klein SP , Bell RM , Bohannan HM , Disney JA , Wilson A (1984). The reliability of clinical and radiographic examinations in the national preventive dentistry demonstration program. Santa Monica, CA: Rand Corp.

Koch GG , Amara IA , Brown BW Jr , Colton T , Gillings DB (1989). A two-period crossover design for the comparison of two active treatments and placebo. Stat Med 8: 487–504.

Kowitz G , Jacobsen J , Meng Z , Lucatorto F (1990). The effects of tartar-control toothpaste on the oral soft tissues. Oral Surg Oral Med Oral Pathol 70: 529–536.

Lachin JM (1981). Introduction to sample size determination and power analysis for clinical trials. Controlled Clin Trials 2: 93–113.

Leske GS , Ripa LW (1980). Ethical and legal considerations associated with clinical field trials. J Dent Res 59(Spec Iss C): 1243–1253.

Levine RJ (1986). Ethics and regulation of clinical research. 2nd ed. Munich: Urban & Schwarzenberg.

Levine RJ , Dennison DK (1997). Randomized clinical trials in periodontology: ethical considerations. Ann Periodontol 2: 83–94.

Louis TA , Lavori PW , Bailar JC III , Polansky M (1984). Crossover and self-controlled designs in clinical research. N Engl J Med 310: 24–31.

Makuch R , Simon R (1978). Sample size requirements for evaluating a conservative therapy. Cancer Treatment Reports (62)7: 1037–1040.

Mancl LA , Hujoel PP , DeRouen TA (2004). Efficiency issues among statistical methods for demonstrating efficacy of caries prevention. J Dent Res 83(Spec Iss C): C95–C98.

Marks RG (2004). The future of web-based clinical research in dentistry. J Dent Res 83(Spec Iss C): C25–C28.

McClendon BJ , Driscoll WS , Abrams AM , Barbano JP (1972). A procedure for estimating sample size in clinical trials of dental caries preventives. J Dent Res 51: 1589–1593.

Medical Research Council (1948). Streptomycin treatment of pulmonary tuberculosis. Br Med J 2: 769–782.

Meinert CL (1981). Organization of multicenter clinical trials. Controlled Clin Trials 1: 305–312.

Meinert CL (1986). Clinical trials: design, conduct and analysis. New York: Oxford.

Meinert CL (1998). Beyond CONSORT: need for improved reporting standards for clinical trials. J Am Med Assoc 278: 1487–1489.

Moher D , Schulz KF , Altman DG , Lepage L , (2001a). Use of the CONSORT statement and quality of reports of randomized trials: a comparative before-and-after evaluation. J Am Med Assoc 285: 1992–1995.

Moher D , Schulz KF , Altman DG (2001b). The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Ann Intern Med 134: 657–662.

Navazesh M (1995). Tartar-control toothpaste as a possible contributory factor in the onset of superficial mucocele: a case report. Spec Care Dentist 15: 74–78.

Needleman I (1999). CONSORT. Consolidated standards of reporting trials (editorial). Br Dent J 186:207.

O'Mullane DM (1976). Efficiency in clinical trials of caries preventive agents and methods. Community Dent Oral Epidemiol 4: 190–194.

Petitti DB (2000). Meta-analysis, decision analysis, and cost-effectiveness analysis. Methods for quantitative synthesis in medicine. 2nd ed. New York: Oxford University Press.

Pledger GW (1992). Basic statistics: importance of adherence. J Clin Res Pharmacoepidemiol 6: 77–81.

Pocock SJ (1983). Clinical trials: a practical approach. New York: Wiley.

Proskin HM , Kingman A , Naleway C , Wozniak WT (1995). Comparative attributes for the description of the relative efficacy of therapeutic agents: general concepts and definitions, and application to the American Dental Association guidelines for the comparison of the clinical anticaries efficacy of fluoride dentifrices. J Clin Dent 6: 176–184.

Radike AW (1972). Examiner error and reversals in diagnosis. In: Proceedings of the conference on the clinical testing of cariostatic agents. Chicago, IL: American Dental Association.

Richards D , Lawrence A , Sackett DL (1997). Bringing an evidence-base to dentistry. Community Dent Health 14(2): 63–65.

Schuirmann DJ (1987). A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm 15: 657–680.

Schwartz D , Lellouch J (1967). Explanatory and pragmatic attitudes in therapeutical trials. J Chron Dis 20: 637–648.

Senn S (1998). Some controversies in planning and analyzing multi-centre trials. Stat Med 17: 1753–1765.

Shapiro SH , Glass KC (2000). Why Sackett's analysis of randomized controlled trials fails, but needn't. Canadian Med Assoc J 163: 834–835.

Slack GL , Martin WJ (1964). The use of a dentifrice containing stannous fluoride in the control of dental caries. Br Dent J 117: 275–280.

Straus SE , Sackett DL (1998). Using research findings in clinical practice. BMJ 317(7154): 339–342.

US Department of Health and Human Services (1991). National Institutes of Health OPRR Reports: Code of Federal Regulations: (45 CFT 46) Protection of Human Subjects (http://ohrp.osophs.dhhs.gov/polasur.htm). Weijer C, Shapiro SH, Glass KC (2000). Why clinical equipoise, and not the uncertainty principle, is the moral underpinning of the RCT. BMJ 321: 756–758.

Weinstein P , Milgrom P , Sanghvi H (1995). Recruitment issues: errors of omission in dental research. J Dent Res 74: 1028–1029.

Wenzel A , Anthonisen PN , Juul MB (2000). Reproducibility in the assessment of caries lesion behavior: a comparison between conventional film and subtraction radiography. Caries Res 34: 214–218.

Whitehead J (1986). Sample sizes for phase II and phase III clinical trials: an integrated approach. Stat Med 5: 459–464.

Wiens BL , Iglewicz B (2000). Design and analysis of three treatment equivalence trials. Control Clin Trials 21: 127–137.

Williams JE , Donnelly CJ , Fulton JT (1967). An appraisal of the necessity for radiographs in clinical trials of caries-inhibitory agents. J Pub Health Dent 27: 54–62.

www.cochrane.org/cochrane/cc-broch.htm#BDL, March (2002).

Zeisel H (1970). Reducing the hazards of human experiments through modifications in research design. Ann NY Acad Sci 169: 475–486.