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Background Durability of response is a clinically relevant dimension of the treatment effect in randomized clinical trials; it is often measured by comparing among the responders the duration of response between the treatment arms. However, since the comparison groups are defined by response (a post-randomization event), it is subject to analysis-by-responder bias, especially if the proportion of responders differs between the arms. Methods Two simple methods are developed that use tumor shrinkage measurements in order to lessen analysis-by-responder bias by generating more comparable patient subsets in the control and experimental arms of the trial. These subsets are then used to estimate between-arm differences in response duration. In the subtraction method, responding patients with the least tumor shrinkage in the treatment arm with more responders are removed from the patient subset for that arm. In the addition method, non-responding patients with the most tumor shrinkage in the treatment arm with fewer responders are added to the patient subset for that arm. In both methods, the numbers of patients subtracted or added are such that the proportion of patients in the modified patient subset is the same as the proportion of responders in the other treatment arm. Results The methods are demonstrated on a hypothetical dataset where they are shown to eliminate analysis-by-responder bias, and on two published analyses of randomized trials that compared the duration of response between the treatment arms. Conclusions The proposed methods can lessen the analysis-by-responder bias. These methods to compare duration of response between treatment arms may provide a useful exploratory analysis to measure treatment efficacy among responders.

Background With the development of targeted agents, the approach to combination cancer therapy has evolved to focus on identifying ways in which pathway inhibition by one agent may enhance the activity of other agents. In theory, this implies that under this new paradigm, agents are no longer required to show single-agent activity, as the pathway inhibited by the targeted agent may only have a therapeutic effect when given with other agents. This raises the question of the extent to which anticancer agents without single-agent activity can contribute to effective combination regimens. Patients and methods We reviewed outcomes of randomised phase 2 combination trials sponsored by the National Cancer Institute Cancer Therapy Evaluation Program that were activated in 2008 to 2017 and noted the single-agent activity of the experimental agents. Results Fifty-three trials were identified, and 50 had available results: 7 (14%), 15 (30%) and 28 (56%) had experimental agents with single-agent activity classified as active, inactive and indeterminate, respectively. Thirteen per cent (95% CI=1.7% to 40.5%) of trials evaluating inactive agents and 11.6% (95% CI=3.9% to 25.1%) of trials evaluating agents without known single-agent activity (pooled inactive and indeterminate) were positive, compared with 42.9% (95% CI=9.9% to 81.6%) for agents with single-agent activity. Conclusions Incorporating agents without documented single-agent activity into treatment regimens is unlikely to produce meaningful improvements in activity unless there is compelling biological rationale. This finding has important implications for the prioritisation of anticancer agents for combination testing, and for the allocation of clinical trial resources.

This study continues our assessment of agreement and disagreement among 25 Chinese and 20 US orthodontists in the ranking for facial attractiveness of end-of-treatment photographs of randomly sampled growing Chinese and white orthodontic patients. The main aims of this article were to (1) measure the overall pattern of agreement between the mean rankings of US and Chinese orthodontists, and (2) measure the strength of agreement between the rankings of the US and Chinese orthodontists for each patient.Each judge independently ranked standard clinical sets of profile, frontal, and frontal-smiling photographs of 43 US patients and 48 Chinese patients. For each patient, a separate mean rank was computed from the responses of each group of judges. Pearson correlations between the mean ranks of the 2 groups of judges were used to measure their overall agreement. Paired and unpaired t tests were used to measure the agreement between the judges of the 2 groups for each patient.The overall agreement between the mean rankings of the US and Chinese judges was very high. For the US patients, the correlation between the Chinese and US judges means was r = 0.92, P0.0001. For the Chinese patients, the analogous value was r = 0.86, P0.0001. Agreement between the 2 groups of judges concerning each patient was also generally strong. For two thirds of the patients, the mean ranks of the US and Chinese judges differed by less than 1 unit in a scale of 12. However, for 6 patients considered individually (5 Chinese and 1 US), the assessment of the 2 groups of judges was statistically significantly different at P values ranging from 0.02 to less than 0.0001, even after the Bonferroni correction.These findings demonstrate that orthodontic clinicians can reliably identify and rank subtle differences between patients, and that differences between judges and between patients can be distinguished at a high level of statistical significance, given appropriate study designs. However, the reasons clinicians give for the differences in their judgments are more difficult to investigate and will require further study.

Introduction: In this study, we assessed agreement and disagreement among pairs of Chinese and US orthodontists in the ranking for “facial attractiveness” of end-of-treatment photographs of growing Chinese and white orthodontic patients. Methods: Two groups of orthodontist-judges participated: from the University of the Pacific, School of Dentistry, in California and from Peking University School and Hospital of Stomatology in China. Each judge independently ranked standard clinical sets of profile, frontal, and frontal-smiling photographs of 43 white patients and 48 Chinese patients. Pearson correlations were generated for a total of 1980 rankings by pairs of judges. Results: The resulting correlations ranged from +0.004 to +0.96 with a median of +0.54. Of these, 18.7% were lower than 0.4; 41.0% were lower than 0.5; 68.8% were lower than 0.6; 91.6% were lower than 0.7; and only 8.4% were greater than 0.7. As had been anticipated, correlations between judges were higher when they ranked patients of their own ethnicity than when they ranked patients of different ethnicity, but the differences were smaller than had been expected. The rankings of no pair of judges correlated negatively. This is to say that no pair of judges, whether of the same or different ethnicity, ranked the patients so that those 1 judge tended to find attractive were consistently found unattractive by the other. Conclusions: The distribution of levels of agreement between pairs of orthodontists did not differ substantially whether the pairs included 2 US orthodontists, 2 Chinese orthodontists, or 1 US and 1 Chinese orthodontist. As might be expected, the pairs of Chinese orthodontists agreed with each other slightly better on average when ranking Chinese patients, and the pairs of US orthodontists agreed with each other slightly better on average when ranking white American patients, but the overall differences were small. These findings appear consistent with the inference that, on average, judgments of “facial attractiveness” by orthodontists at the 2 venues are more similar than had been expected for patients of Chinese and white ethnicity.

Orthodontists typically make judgments of facial attractiveness by examining groupings of profile, full-face, and smiling photographs considered together as a "triplet." The primary objective of this study was to determine the relative contributions of the 3 photographs-each considered separately-to the overall judgment a clinician forms by examining the combination of the 3.End-of-treatment triplet orthodontic photographs of 45 randomly selected orthodontic patients were duplicated. Copies of the profile, full-face, and smiling images were generated, and the images were separated and then pooled by image type for all subjects. Ten judges ranked the 45 photographs of each image type for facial attractiveness in groups of 9 to 12, from "most attractive" to "least attractive." Each judge also ranked the triplet groupings for the same 45 subjects. The mean attractiveness rankings for each type of photograph were then correlated with the mean rankings of each other and the triplets.The rankings of the 3 image types correlated highly with each other and the rankings of the triplets (P.0001). The rankings of the smiling photographs were most predictive of the rankings of the triplets (r = 0.93); those of the profile photographs were the least predictive (r = 0.76). The difference between these correlations was highly statistically significant (P = .0003). It was also possible to test the extent to which the judges' rankings were influenced by sex, original Angle classification, and extraction status of each patient. No statistically significant preferences were found for sex or Angle classification, and only 1 marginally significant preference was found for extraction pattern.Clinician judges demonstrated a high level of agreement in ranking the facial attractiveness of profile, full-face, and smiling photographs of a group of orthodontically treated patients whose actual differences in physical dimensions were relatively small. The judges' rankings of the smiling photographs were significantly better predictors of their rankings of the triplet of each patient than were their rankings of the profile photographs.

Researchers conducting gene expression microarray experiments often are interested in identifying genes that are differentially expressed between two groups of specimens. A straightforward approach to the identification of such “differentially expressed” genes is to perform a univariate analysis of group mean differences for each gene, and then identify those genes that are most statistically significant. However, with the large number of genes typically represented on a microarray, using nominal significance levels (unadjusted for the multiple comparisons) will lead to the identification of many genes that truly are not differentially expressed, “false discoveries.” A reasonable strategy in many situations is to allow a small number of false discoveries, or a small proportion of the identified genes to be false discoveries. Although previous work has considered control for the expected proportion of false discoveries (commonly known as the false discovery rate), we show that these methods may be inadequate. We propose two stepwise permutation-based procedures to control with specified confidence the actual number of false discoveries and approximately the actual proportion of false discoveries. Limited simulation studies demonstrate substantial gain in sensitivity to detect truly differentially expressed genes even when allowing as few as one or two false discoveries. We apply these new methods to analyze a microarray data set consisting of measurements on approximately 9000 genes in paired tumor specimens, collected both before and after chemotherapy on 20 breast cancer patients. The methods described are broadly applicable to the problem of identifying which variables of any large set of measured variables differ between pre-specified groups.

Nonrandomized study designs are proposed that utilize statements by individual clinicians specifying how they would prefer to treat each patient based on the patient's pre-treatment records. Using these stated preferences allows us to eliminate selection biases in an analysis to estimate treatment effects. The analysis of a pilot study using one of the new designs to examine two orthodontic treatments is presented.

This study analyzed the relationship in orthodontically treated adults between upper central incisor displacement measured on lateral cephalograms and apical root resorption measured on anterior periapical x-ray films. A multiple linear regression examined incisor displacements in four directions (retraction, advancement, intrusion, and extrusion) as independent variables, attempting to account for observed differences in the dependent variable, resorption. Mean apical resorption was 1.36 mm (sd +/- 1.46, n = 73). Mean horizontal displacement of the apex was -0.83 mm (sd +/- 1.74, n = 67); mean vertical displacement was 0.19 mm (sd +/- 1.48, n = 67). The regression coefficients for the intercept and for retraction were highly significant; those for extrusion, intrusion, and advancement were not. At the 95% confidence level, an average of 0.99 mm (se = +/- 0.34) of resorption was implied in the absence of root displacement and an average of 0.49 mm (se = +/- 0.14) of resorption was implied per millimeter of retraction. R2 for all four directional displacement variables (DDVs) taken together was only 0.20, which implied that only a relatively small portion of the observed apical resorption could be accounted for by tooth displacement alone. In a secondary set of univariate analyses, the associations between apical resorption and each of 14 additional treatment-related variables were examined. Only Gender, Elapsed Time, and Total Apical Displacement displayed statistically significant associations with apical resorption. Additional multiple regressions were then performed in which the data for each of these three statistically significant variables were considered separately, with the data for the four directional displacement variables. The addition of information on Elapsed Time or Total Apical Displacement did not explain a significant additional portion of the variability in apical resorption. On the other hand, the addition of information on Gender to the information on the four directional displacement variables yielded an R2 value of 0.35, which indicated that these variables taken together could account for approximately a third of the observed variability in apical resorption in this sample.

In a recently reported study, the pretreatment records of each subject in a randomized clinical trial of 148 patients with Class I and Class II malocclusions presenting for orthodontic treatment were evaluated independently by five experienced clinicians (drawn from a panel of 14). The clinicians displayed a higher incidence of agreement with each other than had been expected with respect to the decision as to whether extraction was indicated in each specific case. To improve our understanding of how clinicians made their decisions on whether to extract or not, the records of a subset of 72 subjects randomly selected from the full sample of 148, have now been examined in greater detail. In 21 of these cases, all five clinicians decided to treat without extraction. Among the remaining 51 cases, there were 202 decisions to extract (31 unanimous decision cases and 20 split decision cases). The clinicians cited a total of 469 reasons to support these decisions. Crowding was cited as the first reason in 49% of decisions to extract, followed by incisor protrusion (14%), need for profile correction (8%), Class II severity (5%), and achievement of a stable result (5%). When all the reasons for extraction in each clinician's decision were considered as a group, crowding was cited in 73% of decisions, incisor protrusion in 35%, need for profile correction in 27%, Class II severity in 15% and posttreatment stability in 9%. Tooth size anomalies, midline deviations, reduced growth potential, severity of overjet, maintenance of existing profile, desire to close the bite, periodontal problems, and anticipation of poor cooperation accounted collectively for 12% of the first reasons and were mentioned in 54% of the decisions, implying that these considerations play a consequential, if secondary, role in the decision-making process. All other reasons taken together were mentioned in fewer than 20% of cases. In this sample at least, clinicians focused heavily on appearance-related factors that are qualitatively determinable by physical examination of the surface structures of the face and teeth. They appear to have made primary use of indicators available on study casts and facial photographs and relatively little use of information that is available only on cephalograms or that involves the application of specialized orthodontic theories.

When a trial is stopped early because of a specific toxicity, it may be important to summarize the statistical evidence for stopping. Such a summary needs to take into account the sequential nature of the stopping rule. We address some practical issues involved in analyzing such toxicity data coming from a trial that was stopped after the fourth patient was evaluated.

This study quantifies the differences in the perceived pattern of mandibular remodeling when two different methods are used to superimpose roentgenographic images of the mandible. Lateral cephalograms for a group of subjects with metallic implants of the Bjork type were superimposed twice; first on the metallic implants and then independently on mandibular anatomic structures according to a common "best fit" rule. In this article, we compare the between-superimposition differences in the perceived displacements of condyle, gonion, menton, pogonion, and Point B. Mean differences between the two superimpositional techniques were smaller than had been anticipated. For the 7-year time interval between 8.5 and 15.5 years, the largest mean differences between methods were 2.70 mm in the horizontal direction at condyle, 1.90 mm in the vertical direction at condyle, and 1.52 mm in the vertical direction at gonion. None of the other between-superimposition differences had a mean value in excess of 1 mm. The individual case variability between the two methods was, however, quite considerable, a finding that we believe has bearing on the confidence that can be placed in individual case analyses in clinical orthodontics. A preliminary attempt has been made to represent and discuss the magnitude of this problem.

We report the results of a study aimed at quantifying remodeling of mandibular surfaces in a sample of growing children who represent those usually treated by orthodontists in the mixed and early adult dentition. The sample, 31 patients with metallic implants of the Bjork-type, was monitored at annual intervals between 8 1/2 and 15 1/2 years of age. (Maxillary remodeling changes for the sample have been reported earlier.) The present article reports findings concerning changes at condyle, gonion, menton, pogonion, and point B as identified on lateral cephalograms. Data are reported in the Frankfort plane frame of reference with the cephalograms from different time points superimposed on the metallic implants. Mean displacement at condyle was larger than that at any other landmark and was similar in magnitude and direction to the observations of Bjork when the difference in orientation of the vertical axis in the two studies is taken into account. The mean displacement of gonion was in an upward and backward direction at an angle of approximately 45 degrees to the Frankfort plane. Mean displacements at menton and pogonion were in a downward and backward direction but were very small. Mean displacement at point B was somewhat greater than that of menton and gonion, oriented in an upward and backward direction. Individual variation for most of the parameters measured was sufficiently large to warrant the inference that caution should be used when mean values are applied to the analysis of individual cases.

The standard design for randomised clinical trials may be inappropriate when the clinician believes that one of the treatments being tested is superior for the patient, or when the clinician has a preference for one of the treatments. For such instances the suggestion is that the patient is randomly allocated to treatment only when there is clinical disagreement about treatment of choice for that patient, and then the patient is assigned to a clinician who had thought that the regimen allocated is the one most appropriate for that patient.

Introduction The objective of this pilot randomized clinical trial was to investigate the relative effectiveness of anchorage conservation of en-masse and 2-step retraction techniques during maximum anchorage treatment in patients with Angle Class I and Class II malocclusions. Methods Sixty-four growing subjects (25 boys, 39 girls; 10.2-15.9 years old) who required maximum anchorage were randomized to 2 treatment techniques: en-masse retraction (n = 32) and 2-step retraction (n = 32); the groups were stratified by sex and starting age. Each patient was treated by a full-time clinic instructor experienced in the use of both retraction techniques at the orthodontic clinic of Peking University School of Stomatology in China. All patients used headgear, and most had transpalatal appliances. Lateral cephalograms taken before treatment and at the end of treatment were used to evaluate treatment-associated changes. Differences in maxillary molar mesial displacement and maxillary incisor retraction were measured with the before and after treatment tracings superimposed on the anatomic best fit of the palatal structures. Differences in mesial displacement of the maxillary first molar were compared between the 2 treatment techniques, between sexes, and between different starting-age groups. Results Average mesial displacement of the maxillary first molar was slightly less in the en-masse group than in the 2-step group (mean, –0.36 mm; 95% CI, –1.42 to 0.71 mm). The average mesial displacement of the maxillary first molar for both treatment groups pooled (n = 63, because 1 patient was lost to follow-up) was 4.3 ± 2.1 mm (mean ± standard deviation). Boys had significantly more mesial displacement than girls (mean difference, 1.3 mm; P Conclusions Average mesial displacement of the maxillary first molar with 2-step retraction was slightly greater than that for en-masse retraction, but the difference did not reach statistical significance. This finding appears to contradict the belief of many clinicians that 2-step canine retraction is more effective than en-masse retraction in preventing clinically meaningful anchorage loss.

Introduction Orthodontists rely on esthetic judgments from facial photographs. Concordance between estimates of facial attractiveness made from lateral cephalograms and those made from clinical photographs has not been determined. We conducted a preliminary examination to correlate clinicians' rankings of facial attractiveness from standardized end-of-treatment facial photographs (Photo Attractiveness Rank) with cephalometric measurements of facial attractiveness made for the same subjects at the same time. Methods Forty-five Chinese and US orthodontic clinicians ranked end-of-treatment photographs of separate samples of 45 US and 48 Chinese adolescent patients for facial attractiveness. Separately for each sample, the photographic rankings were correlated with the values of 21 conventional hard- and soft-tissue measures from lateral cephalograms taken at the same visits as the photographs. Results Among US patients, higher rank for facial attractiveness on the photographs was strongly associated with higher values for profile angle, chin prominence, lower lip prominence, and Z-angle, and also with lower values for angle of convexity, H-angle, and ANB. Among Chinese patients, higher rank for facial attractiveness on the photographs was strongly associated with higher values for Z-angle and chin prominence, and also with lower values for angle of convexity, H-angle, B-line to upper lip, and mandibular plane angle. Chinese patients whose %lower face height values approximated the ethnic “ideal” (54%) tended to rank higher for facial attractiveness than patients with either higher or lower values for %lower face height. The absolute values of the correlations for the 7 US measures noted above ranged from 0.41 to 0.59; those of the 7 Chinese measures ranged from 0.39 to 0.49.The P value of the least statistically significant of these 14 correlations was 0.006, unadjusted for multiple comparisons. On the other hand, many cephalometric measures believed by clinicians to be indicators of facial attractiveness failed to correlate with facial attractiveness rank for either ethnicity at even the P Conclusions In general, there was less association than expected or desired between objective measurements on the lateral cephalograms and clinicians' rankings of facial attractiveness on sets of clinical photographs.

Introduction Orthodontists rely on esthetic judgments from facial photographs. Concordance between estimates of facial attractiveness made from lateral cephalograms and those made from clinical photographs has not been determined. We conducted a preliminary examination to correlate clinicians' rankings of facial attractiveness from standardized end-of-treatment facial photographs (Photo Attractiveness Rank) with cephalometric measurements of facial attractiveness made for the same subjects at the same time. Methods Forty-five Chinese and US orthodontic clinicians ranked end-of-treatment photographs of separate samples of 45 US and 48 Chinese adolescent patients for facial attractiveness. Separately for each sample, the photographic rankings were correlated with the values of 21 conventional hard- and soft-tissue measures from lateral cephalograms taken at the same visits as the photographs. Results Among US patients, higher rank for facial attractiveness on the photographs was strongly associated with higher values for profile angle, chin prominence, lower lip prominence, and Z-angle, and also with lower values for angle of convexity, H-angle, and ANB. Among Chinese patients, higher rank for facial attractiveness on the photographs was strongly associated with higher values for Z-angle and chin prominence, and also with lower values for angle of convexity, H-angle, B-line to upper lip, and mandibular plane angle. Chinese patients whose %lower face height values approximated the ethnic “ideal” (54%) tended to rank higher for facial attractiveness than patients with either higher or lower values for %lower face height. The absolute values of the correlations for the 7 US measures noted above ranged from 0.41 to 0.59; those of the 7 Chinese measures ranged from 0.39 to 0.49.The P value of the least statistically significant of these 14 correlations was 0.006, unadjusted for multiple comparisons. On the other hand, many cephalometric measures believed by clinicians to be indicators of facial attractiveness failed to correlate with facial attractiveness rank for either ethnicity at even the P

Cancer researchers show a continuing interest in assessing quality of life in clinical trials [l]. The standard endpoints in a comparative cancer clinical trial are survival and/or time to disease progression, tumor response, and treatment toxicities. Assessing quality of life is often more difficult than assessing these standard endpoints, especially if one attempts to obtain relatively complete (nonmissing) data. Moreover, the clinical interpretation of quality-of-life results can be more difficult than understanding the magnitude of differences in survival, response, or toxicity. A natural question is whether the information provided by quality-of-life assessments adds to the interpretation of cancer trial results beyond the analysis of standard endpoints. Two papers widely quoted in this regard are the one that compares amputation to limb-sparing surgery plus irradiation for patients with extremity softtissue sarcoma [2] and the one that compares intermittent to continuous chemotherapy for patients with metastatic breast cancer [3]. In the sarcoma trial, nine patients were randomized and assessed for the amputation treatment, and 17 for the limb-sparing treatment (the randomization was 2:l). Contrary to the investigators’ a priori hypothesis, quality of life assessment suggested that the limb-sparing surgery plus irradiation did not provide improved quality of life and, in fact, was worse on some measures. In the breast cancer trial, all the quality of life endpoints favored the continuous chemotherapy. The standard endpoints also favored the continuous chemotherapy, so in some sense one could say that the quality of life assessment did not add to the comparison of the treatment arms. The quality of life assessment did add to the interpretation of the results of the trial, because the designers of the trial expected that the continuous chemotherapy would lead to worse quality of life. Unfortunately, only 83 patients had self-assessed quality of life measurements available for the main comparative analysis, although apparently 196 patients were potentially available. Additionally, the times of quality of life assessment were apparently not balanced between the treatment arms.

Natural cell mediated cytotoxicity has been expressed as percent cytotoxicity, as the slope of the titration curve obtained by testing different effector: target cell ratios, and as lytic units. Objections can be raised to each method as used. The present report involves the study of cytotoxicity by subpopulations of lymphocytes obtained by Percoll density gradient centrifugation. The subpopulations vary greatly in cytotoxic activity, making accurate comparisons by traditional means difficult. A method was therefore developed for making objective comparisons between activities of subpopulations of lymphocytes. Cytotoxicity titration curves, which were sigmoidal on linear-linear plots, were found to best fit the sigmoidal curves described by the Von Krogh equation. A best fitting scale family of curves having the identical maximum cytotoxicity and shape parameter was fitted simultaneously to cytotoxicity measurements obtained by titrating all subpopulations of effector cells obtained from each patient. Values expressing relative cytotoxicities were obtained from the ratios of the scale parameters of the different curves or by obtaining lytic units from the fitted curves. In addition to the enriched natural cytotoxic activity found among the lighter cells obtained by Percoll density gradient centrifugation, activity was also increased among cells sedimenting at the very bottom of the gradient. This was found in subpopulations of cells obtained from 16/21 gradients in tests against K562 and in subpopulations obtained from both of 2 gradients in tests against Daudi cells. These findings are consistent with the existence of at least 2 subpopulations of lymphocytes which can mediate natural cytotoxicity, and which are separable by density.

Lateral skull radiographs for a set of 31 human subjects were examined using computer-aided methods in an attempt to quantify modal trends of maxillary remodeling during the mixed dentition and adolescent growth periods. Cumulative changes in position of anterior nasal spine (ANS), posterior nasal spine (PNS), and Point A are reported at annual intervals relative to superimposition on previously placed maxillary metallic implants. This in vivo longitudinal study confirms at a high level of confidence earlier findings by Enlow, Björk, Melsen, and others to the effect that the superior surface of the maxilla remodels downward during the period of growth and development being investigated. However, the inter-individual variability is relatively large, the mean magnitudes of change are relatively small, and the rate of change appears to diminish by 13.5 years. For the 19 subjects for whom data were available for the time interval from 8.5 to 15.5 years, mean downward remodeling at PNS was 2.50 mm with a standard deviation of 2.23 mm. At ANS, corresponding mean value was 1.56 mm with a standard deviation of 2.92 mm. Mean rotation of the ANS-PNS line relative to the implant line was 1.1 degree in the "forward" direction. However, this rotational change was particularly variable with a standard deviation of 4.6 degrees and a range of 11.3 degrees "forward" to 6.7 degrees "backward." The study provides strong evidence that the palate elongates anteroposteriorly mainly by the backward remodeling of structures located posterior to the region in which the implants were placed. There is also evidence that supports the idea of modal resorptive remodeling at ANS and PNS, but here the data are somewhat more equivocal. It appears likely, but not certain, that there are real differences in the modal patterns of remodeling between treated and untreated subjects. Because of problems associated with overfragmentation of the sample, sex differences were not investigated.

This article analyzes differences in displacement of ANS and of the upper first molar when different vectors of force are delivered to the maxilla in non-full-banded Phase I mixed-dentition treatment of Class II malocclusion. The sample is identical to that for which we have previously reported differences in change in several key measures of mandibular and facial shape. It includes a cervical-traction group, a high-pull-to-upper-molar group, a modified-activator group, and an untreated Class II control group. Using newly developed computer-conducted procedures, which are described, we have been able to partition the orthodontic and orthopedic components of upper molar displacement and also to isolate treatment effects from those attributable to spontaneous growth and development. In the region of ANS, small but statistically significant and clinically meaningful differences were noted between treatments. When the intercurrent effects of growth and development had been factored out (Table III), orthopedic distal displacement of ANS was significantly greater in the high-pull and cervical groups than in the activator group. Orthopedic downward displacement of ANS was seen to be significantly greater in the cervical group than in the high-pull and activator groups. In the region of the first molar cusp, mean distal displacement of the tooth as an orthopedic effect was found to be almost identical in the cervical and high-pull groups (although variability was greater in the cervical group), but the mean orthodontic effect was significantly greater in the high-pull group than in the cervical group. In the cervical group, where relatively light forces were used for relatively long treatment periods on average, more of the total distal displacement of the upper molar was of an orthopedic character than of an orthodontic character. Conversely, in the high-pull group, in which relatively heavier forces tended to be used for briefer treatment periods, most of the distal displacement at the upper molar was of an orthodontic character. These observations are contrary to expectations from conventional orthodontic theory. In the activator-treated group, roughly equal components of the treatment-associated distal displacement of the upper molar were of the orthodontic and orthopedic types. As concerns changes in the vertical direction in the region of the molar cusp, significant intrusion of both the orthopedic and orthodontic types was seen in the high-pull sample as compared to each of the other groups examined.(ABSTRACT TRUNCATED AT 400 WORDS)

The estimation of the utility of matching in completed case-control studies is examined. The utility is defined in terms of providing an estimate of a more valid odds ratio than the crude odds ratio, and in providing a more efficient study than an unmatched study with a stratified analysis. Methods are given to estimate the utility of frequency-matching in a completed study where the cases and controls are matched into broad strata such as age or decade of birth. An example from the literature demonstrates the technique. Since the proposed analysis requires knowledge of the proportions of individuals in the study population associated with each stratum, it is recommended that estimates of these proportions be given in the results of frequency-matched case-control studies. For pair-matching where each pair is regarded as defining its own stratum (such as with neighborhood or friend controls) it is shown to be impossible to estimate the utility of the matching from a completed study. In particular, it is incorrect for either frequency- or pair-matching to try to estimate the utility of matching by performing an unmatched analysis on a completed case-control study.

Legitimate questions exist concerning the degree to which routine orthodontic treatment alters face form. To the extent that such alterations do occur, the delivery of different vectors should result in different sorts of skeletal change. In this study, we have attempted to discern and quantify differences in the rates of change of nine linear measures of mandibular and facial proportions during the course of Phase 1 treatment for the correction of Class II mixed-dentition malocclusion. The analysis took the form of a series of computer-conducted tests performed upon a previously reported tape-stored numerical data base which had been constructed earlier by digitizing pre- and posttreatment lateral cephalograms for a large group of Class II subjects. Rates of change for the nine linear measures were computed separately for samples of subjects treated with cervical face-bow, high-pull face-bow, and activator type intraoral appliances as well as for a control group of untreated Class II subjects. Statistically significant between-treatment differences which we believe are large enough to be of clinical importance were detected for several measures. As compared to the control group, a statistically significant rate of increase in condyle-pogonion distance was found in the intraoral group. Such an observation is consistent with the hypothesis of treatment-associated alteration of growth pattern in the region of the condyle. To our considerable surprise, the cervical group exhibited a similar statistically significant rate of increase in condyle-pogonion distance which is as yet unexplained. In general, rates of increase in measures of anterior face height had higher values in the cervical group than in the control group, implying that consideration should be given to avoiding the use of this treatment modality in patients for whom facial elongation during treatment would be undesirable. The cervical group also exhibited a statistically significant rate of increase in ramus height. Such an effect would tend to keep mandibular plane orientation relatively unchanged in the presence of increase in anterior face height, helping to explain our previously reported findings as to the relative constancy of mandibular plane angle. In the high-pull-treatment group, rates of increase in ramus height and condyle-pogonion distance were significantly lower than those in the control group and rates of increase in lower face height and anterior face height were significantly lower than those in the cervical group. In all three treatment groups, the rate of increase in mandibular body length was less than in the untreated control group, though only in the cervical group was this effect large enough to be statistically significant.

An experiment was conducted in an attempt to determine empirically how effective a number of expert clinicians were at differentiating "backward rotators" from "forward rotators" on the basis of head-film information which might reasonably have been available to them prior to instituting treatment for the correction of Class II malocclusion. As a result of a previously reported ongoing study, pre- and posttreatment head films were available for 188 patients treated in the mixed dentition for the correction of Class II malocclusion and for 50 untreated Class II subjects. These subjects were divided into 14 groups (average size of group, 17; range, 6 to 23) solely on the basis of type of treatment and the clinician from whose clinic the records had originated. From within each group, we selected the two or three subjects who had exhibited the most extreme backward rotation and the two or three subjects who had exhibited the most extreme forward rotation of the mandible during the interval between films. The sole criterion for classification was magnitude of change in the mandibular plane angle of Downs between the pre- and posttreatment films of each patient. The resulting sample contained 32 backward-rotator subjects and 32 forward-rotator subjects. Five expert judges (mean clinical experience, 28 years) were asked to identify the backward-rotator subjects by examination of the pretreatment films. The findings may be summarized as follows: (1) No judge performed significantly better than chance. (2) There was strong evidence that the judges used a shared, though relatively ineffective, set of rules in making their discriminations between forward and backward rotators. (3) Statistical analysis of the predictive power of a set of standard cephalometric measurements which had previously been made for this set of subjects indicated that the numerical data also failed to identify potential backward rotators at a rate significantly better than chance. We infer from these findings that the ability of clinicians to identify backward rotators on the basis of information available at the outset of treatment is poor. Hence, we believe that it is unlikely that such predictions play any consequential operational role in the planning of successful orthodontic therapy at the present state of the art.

This article analyzes differences in the measured displacement of the condyle and of pogonion when different vectors of force are delivered to the maxilla in the course of non-full-banded, Phase 1, mixed-dentition treatment for the correction of Class II malocclusion. The 238-case sample is identical to that for which changes in other parameters of facial form have been reported previously.37–39 Relative to superimposition on anterior cranial base and measured in a Frankfort-plane-determined coordinate system, we have attempted to identify and quantitate (1) the displacement of each structure which results from local remodeling and (2) the displacement of each structure which occurs as a secondary consequence of changes in other regions of the skull. We have also attempted to isolate treatment effects from those attributable to spontaneous growth and development. At the condyle, we note that in all three treatment groups and in the control group there is a small but real downward and backward displacement of the glenoid fossa. This change is not treatment induced but, rather, is associated with spontaneous growth and development. (See Fig. 5.) Some interesting differences in pattern of “growth at the condyle” were noted between samples. In the intraoral (modified activator) sample, there were small but statistically significant increases in growth rate as compared to the untreated group of Class II controls. To our surprise, similar statistically significant increases over the growth rate of the control group were noted in the cervical sample. (See Table III, variables 17 and 18.) Small but statistically significant differences between treatments were also noted in the patterns of change at pogonion. As compared to the untreated control group, the rate of total displacement in the modified activator group was significantly greater in the forward direction, while the rate of total displacement in the cervical group was significantly greater in the downward direction. There were no statistically significant differences in the rate of total displacement of pogonion between the high-pull sample and the control sample. (See Table IV, variables 21 and 22.)