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PubMed2000

Passive ankle stiffness in subjects with diabetes and peripheral neuropathy versus an age-matched comparison group.

BACKGROUND AND PURPOSE: Patients with diabetes mellitus and peripheral neuropathy (DM and PN) often complain of joint stiffness. Although stiffness may contribute to some of the impairments and functional limitations found in these patients, it has not been quantified in this population. The purpose of this study was to quantify and compare passive ankle stiffness and dorsiflexion (DF) range of motion in subjects with DM and PN versus an age-matched comparison group. SUBJECTS: Thirty-four subjects were tested (17 subjects with DM and PN and 17 subjects in an age-matched comparison group). There were 10 male subjects and 7 female subjects in each group. METHODS: A Kin-Com dynamometer was used to measure passive plantar flexor torque as each subject's ankle was moved from plantar flexion into dorsiflexion at 60(/s. The following variables were compared using a Student t test: initial angle (angle of onset of plantar flexor torque), maximal dorsiflexion angle, plantar flexor muscle excursion (difference between initial angle and maximal dorsiflexion angle), slope of the first half of the plantar flexor torque curve (stiffness 1 measurement), and slope of the second half of the plantar flexor torque curve (stiffness 2 measurement). RESULTS: The subjects with DM and PN had smaller maximal dorsiflexion angles and less plantar flexor muscle excursion than the comparison group. There was no difference in initial angle, stiffness 1 measurement, or stiffness 2 measurement. CONCLUSION AND DISCUSSION: Although the subjects with DM and PN had less dorsiflexion range of motion than did the comparison group, there was no difference in stiffness between the groups. This finding suggests that people with DM and PN have "short" versus "stiff" plantar flexor muscles.

Adult↗

PubMed2002

Comparison of the developmental and reproductive toxicity of diethylstilbestrol administered to rats in utero, lactationally, preweaning, or postweaning.

The objective of the study was to determine which period of exposure produces the most marked effects on the reproductive capacity and sexual development of the rat, with particular emphasis on the relative sensitivity of in utero and postnatal exposures. The endocrine active chemical, diethylstilbestrol (DES) was used as an agent known to affect many of the endpoints examined. Hitherto, such comparisons have been made between studies, rather than within a study. Our data will be helpful in the interpretation of future multigenerational assay data. In preliminary studies, DES was shown to be active in the immature rat uterotrophic assay with a lowest detected dose of 0.05 mg DES/kg body weight by sc injection and 10 mg DES/l (1.6 mg DES/kg body weight) by administration in drinking water. A dose of 60 microg DES/l drinking water ( approximately 6.5mg DES/kg body weight/day) was selected for the main study since this represented the midpoint of the drinking water uterotrophic dose response and produced no overt maternal toxicity. The study used 10 groups of concomitantly pregnant animals, including 2 control groups. The first comparison was between the effects of exposure to DES in utero, and exposure from conception to weaning. Another group of animals was exposed to DES in utero and cross-fostered to untreated pregnant females to prevent lactational transfer of DES to pups. Two groups were exposed to DES neonatally, either from birth to postnatal day (PND) 10 (pups thus having only lactational exposure), or from birth until weaning (PND 21; pups thus having both lactational exposure and self-exposure via drinking water). In addition, a dose response study to DES was conducted on animals exposed from weaning to PND 100, when the first phase of the study was terminated. Pups exposed to DES in utero and pups exposed from weaning to PND 100 were bred to assess fertility of the F1 animals and the sexual development of F2 offspring. This last comparison was to determine the extent to which weanling rats could be used in endocrine toxicity studies to assess their potential to show activity in utero. The most sensitive period of exposure for inducing developmental effects in F1 animals was from weaning onwards. The neonatal to weaning period (PND 1-21) was the next most sensitive. Essentially no effects were induced in F1 animals exposed in utero. No effects of any kind were observed in animals only exposed over the early neonatal period of PND 1-10. The mean day of vaginal opening, testes descent, and prepuce separation was only altered in groups where postnatal exposure to DES continued beyond PND 10, or was started at weaning. No changes were observed in anogenital distance or caudal sperm counts. Some changes in organ weights were observed, but the interpretation of these was often confused by concomitant changes in body weight. In general, histopathological examination of tissues yielded no additional information. In breeding studies with animals exposed to DES in utero, or from weaning, reduced litter sizes and marginal advances in the day of vaginal opening were observed in the offspring, together with changes in organ weights. However, no unique sensitivity was noted for exposure in utero. Evaluation of the several exposure periods and the many markers monitored in this study may have individual strengths in individual cases, but when rigorously compared using the reference estrogen DES, many preconceptions regarding their absolute or relative value were not upheld. Further, each of these markers is subject to natural variability, as demonstrated by comparisons made among the 5 separate control groups available in parts of the present study. This variability increases the chance that small changes observed in endocrine toxicity studies employing small group sizes and a single control group, or no concomitant control group, may be artifactual. The most marked effects observed in this study were on the developmental landmarks in the F1 animals induced by exposures after PND 10. Some effects on developmental landmarks and organ weights were observed in F2 animals following exposure either in utero or postweaning. This study therefore does not establish a unique role for exposures in utero or during the early neonatal period.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

The effect of comparison films upon resident interpretation of pediatric chest radiographs.

Radiology residents beginning training or at the end of the first, second, or third year of training served as observers in a study of the effect of previous or comparison radiographs upon the interpretation of current pediatric chest films. For physicians early in residency, a substantial improvement in detection accuracy occurred when a prior normal film was presented with each examination. Facilitation of a lesser magnitude was obtained for specific diagnosis (classification) of lesions. Thus, while normal comparison films may help reveal to the newer resident that an abnormality exists, it does less to reveal the nature of that abnormality. For physicians late in residency, the same difference in detection accuracy between groups was obtained, but the magnitude of the difference was quite small. However, substantially higher accuracy of specific diagnosis resulted when comparison films were available. While neither normal nor abnormal comparison films markedly changes the accuracy of detection by advanced residents, both improve diagnosis.

Educational Measurement↗

PubMed1987

Normative data and control studies of flash VEP's for comparison to a clinical population.

The effects of aging, interocular comparisons, pupil dilation, iris pigmentation, and simulated cataracts on bright flash visual evoked potentials (VEP's) of normal observers were studied to assess the flash VEP as a potential predictor of postsurgical visual function in cataract patients. Seventy-six observers (from 20 to 80 years old) were tested for age differences in flash VEP's. Implicit time measures for transient responses increased significantly as a function of age, but neither transient nor steady-state response amplitudes were altered significantly. Moreover, no significant changes in VEP's occurred as a function of interocular comparisons, pupil dilation, or differences in iris pigmentation of normal observers. Simulation of cataracts with 14 observers did not affect implicit time measures, but did change response amplitudes significantly. Therefore, implicit time measures of cataract patients should be compared either to those of normal age-matched controls or, in the case of a unilateral problem, to the normal fellow eye. Delayed implicit time measures, after the appropriate comparison, suggest optic nerve/pathway dysfunction. However, comparisons of amplitude measures require compensation for opacity density.

Adult↗

PubMed1997

P1-latency interroot comparison enhances the validity of scalp-recorded somatosensory-evoked potentials to diagnose nerve root dysfunction in sciatica.

STUDY DESIGN: A prospective validity study was done of scalp-recorded somatosensory-evoked potentials as a diagnostic procedure to show lumbosacral radiculopathy in 100 consecutive patients with unilateral or bilateral sciatica. OBJECTIVE: To determine the validity gained by the use of P1-latency interroot comparison to show P1-latency prolongation. SUMMARY OF THE BACKGROUND DATA: The validity of scalp-recorded somatosensory-evoked potentials in diagnosing lumbosacral radiculopathy has been debated and is uncertain. METHOD: Sensory nerves representing nerve roots L4, L5, and S1 were stimulated bilaterally. Height-corrected P1-latency, two new P1-interroot comparison-based criteria, and absence of P1 were studied. The gold standard was defined as clinically-involved nerve roots with radiologic nerve root compression. The false-positive nerve root compression rate was determined, and the gold standard was corrected accordingly. Clinically relevant cut-off values were defined by multilevel likelihood ratio analysis. RESULTS: The positive and negative likelihood ratios of P1-latency prolongation were 6.79 and 0.53, respectively, for the gold standard, and 10.57 and 0.21, respectively, for the corrected gold standard. The validity was not reduced when scalp-recorded, somatosensory-evoked potentials were blinded to the radiologic results. Absence of P1 was associated to the gold standard and the corrected gold standard. Compared with the combined use of P1-latency interside difference and height-corrected latency, the combination of P1-interroot comparison and height-corrected P1-latency increased the sensitivity by 20% for the gold standard and 32% for the corrected gold standard, and when absent P1 was added, the overall sensitivity was 53% for the gold standard and 81% for the corrected gold standard. The corresponding specificity was 92%, and in asymptomatic nerve roots it was 98%. CONCLUSION: The P1-interroot comparison permits the use of scalp-recorded somatosensory-evoked potentials as a contributory "rule in" procedure in patients with sciatica.

Adolescent↗

PubMed2006

Comparison of natural background dose rates for residents of the Amargosa Valley, NV, to those in Leadville, CO, and the states of Colorado and Nevada.

In the latter half of 2005, the U.S. Environmental Protection Agency (U.S. EPA) published a Proposed Rule (40 CFR Part 197) for establishing a dose rate standard for limiting radionuclide releases from the proposed Yucca Mountain high-level radioactive waste repository during the time period from 10 to 10 years after closure. The proposed standard was based on the difference in the estimated dose rate from natural background in the Amargosa Valley and the "average annual background radiation" for the State of Colorado. As defined by the U.S. EPA, "natural background radiation consists of external exposures from cosmic and terrestrial sources, and internal exposures from indoor exposures to naturally-occurring radon." On the basis of its assessments, the U.S. EPA estimated that the difference in the dose rate in the two identified areas was 3.5 mSv y. The purpose of this paper is to provide an independent evaluation and review of this estimate. One of the first observations was that, because site-specific dose rate measurements for the Amargosa Valley "were not available," the dose rates for various sources of natural background in that area, used by the U.S. EPA in its assessment, were based on modifications of the average values for the State of Nevada. A second observation was that the conversion coefficient applied in estimating the dose rates due to exposures to indoor radon and its decay products was a factor of >2 higher than the currently internationally accepted value. Further review revealed that site-specific data for many natural background sources in the Amargosa Valley were available. One particularly important observation was that about 91% of the residents of that area live in mobile homes which, due to their construction and design, have indoor radon concentrations comparable to, or less than, those outdoors. For that reason, alone, the U.S. EPA estimate of the average dose rate for residents of the Amargosa Valley, due to exposures to indoor radon, was not valid. For purposes of the comparisons in this paper, site-specific dose rates were estimated for all major natural background sources of exposure to residents of the Amargosa Valley, and those in Leadville, CO. The latter community was selected for comparison because of its altitude (3,200 m) and accompanying relatively high cosmic radiation dose rate, and the fact the size of its population is comparable to that of the Amargosa Valley. Another reason for this selection was that a comparison of the average natural background dose rate in the Amargosa Valley to that for the State of Colorado is not suitable because it fails to consider those locations within the State that have dose rates that are higher than the average. Nonetheless, for completeness, and to provide a number that could be compared to the U.S. EPA estimated difference, similar comparisons of the estimated dose rate in the Amargosa Valley to those for average residents of the States of Colorado and Nevada were included in the assessments that follow. The outcome showed that the estimated dose rates in Leadville, the State of Colorado, and the State of Nevada, were higher than those in the Amargosa Valley by 3.94 +/- 1.09, 2.54 +/- 2.18, and 0.95 +/- 0.82 mSv y, respectively. Associated uncertainties were highest for the estimated dose rates due to exposures to radon and its decay products. Had the systematic errors in the radon dose conversion coefficient and the random distribution in radon concentrations been included, the overall uncertainty in the total dose rate estimates could have been as high as 150%.

Air Pollution, Indoor↗

PubMed1995

A comparison of two independently determined structures of trypanothione reductase from Crithidia fasciculata.

The enzyme trypanothione reductase (TR) is unique to trypanosomes and leishmania parasites, the causal agents of several important medical and veterinary tropical diseases. TR helps regulate the intracellular reducing environment of the parasite and it has been identified as a target for developing novel chemotherapeutic agents by structure-aided drug design. For this purpose it is essential to have confidence in the structural detail of the molecular target. Two independent studies of Crithidia fasciculata TR at medium resolution, in different space groups have afforded an opportunity to assess the reliability of the models. We summarize the important methodological details of each analysis and present a comparison of the geometry, thermal parameters and three-dimensional structure of the models. Particular attention has been paid to the disulfide substrate-binding site which is the area of most interest with respect to enzyme inhibition. The comparison has shown that the structures agree closely with Calpha atoms superposing with an r.m.s. of less than 0.5 A. The consistency of the models gives a high level of confidence that they are suitable for computer-aided drug design. The conformation of many side chains in the active site, in particular the catalytic residues, are well conserved in both structures. However, the comparison indicates a difference in the conformation of Trp21 and Met113 which together form a hydrophobic patch on the rim of the active-site cleft and interact with the spermidine moiety of the substrate. Consideration of the electron-density maps together with the structural comparison indicates that there is some conformational flexibility in this region of the active site. This heterogeneity may be used in the recognition of the substrate by the enzyme and should be considered when mapping out the size, shape and chemical properties of the active site.

Journal Article↗

PubMed1989

Procedure for quantitative comparison of ground reaction data.

Measurement of ground reaction forces has been largely adopted for evaluation of gait disorders even if the discussion of obtained results and their comparison with those from normal locomotion are generally related to a purely visual interpretation of the pattern morphology or, at least, to the assessment of a limited number of parameters such as maximal amplitude of force, number of maxima in the envelope, presence of one minimum or more, etc. This paper describes an analytical method for a quantitative and detailed comparison of different ground reaction force patterns. It is based on a suitable processing of the 3-D components of the ground reaction force and is essentially composed of three main frames: verification of the regular recurrence of measurement conditions, normalization, and data comparison. The first frame is to check that the acquired data are not affected by inertial predominance in the direction of progression. Normalization involves the amplitude of force, the application point displacements and the stance-phase duration. Data comparison utilizes a dedicated implementation of an appropriate statistical approach to estimate significant differences between two suitable and typical ground reaction force patterns. In order to show practical examples of the whole analytical procedure, two cases are also presented in detail.

Adult↗

PubMed2001

Comparison of chemical screening and ranking approaches: the waste minimization prioritization tool versus toxic equivalency potentials.

Chemical screening in the United States is often conducted using scoring and ranking methodologies. Linked models accounting for chemical fate, exposure, and toxicological effects are generally preferred in Europe and in product Life Cycle Assessment. For the first time, a comparison is presented in this article of two of the prominent, but structurally different methodologies adopted to help screen and rank chemicals and chemical emissions data. Results for 250 chemicals are presented, with a focus on 12 chemicals of interest in the United Nations Environment Programme's Persistent Organic Pollutants global treaty negotiations. These results help to illustrate the significance of described structural differences and to assess the correlation between the methodologies. The scope of the comparison was restricted here to human health, although the insights would be equally useful in the context of the health of ecosystems. Illustrating the current types of chemical screening and emissions comparison approaches, the relative significance of the scenario and structural differences of the Waste Minimization Prioritization Tool (WMPT) and the Toxic Equivalency Potential (TEP) methodologies are analyzed. The WMPT facilitates comparison in terms of key physical-chemical properties. Measures for Persistence, Bioaccumulation, and Toxicity (PBT) are calculated. Each PBT measure is scored and then these scores are added to provide a single measure of relative concern. TEPs account for chemical fate, multipathway exposure, and toxicity using a model-based approach. This model structure is sometimes considered to provide a less subjective representation of environmental mechanisms, and, hence, an improved basis for screening. Nevertheless, a strong relationship exists between the two approaches and both have their limitations.

Biological Availability↗

PubMed2003

How reassuring are risk comparisons to pollution standards and emission limits?

Pollutant emissions or ambient levels are often justified by reference to a higher benchmark, such as a public health standard or permit limit. However, does this risk comparison persuade the public audiences to whom it is frequently directed that such pollution levels are "acceptable"? A substantial proportion of people living within one mile of New Jersey's industrial facilities, perhaps as much as half, is indeed reassured by a comparison to such benchmarks. Positive attitudes toward discharge limits were linked to speaking English at home; positive attitudes toward drinking water standards were associated with seeing local benefits of industry as outweighing its risks, not speaking English, and relative youth (49 years old or less). Three scenarios involving drinking water contamination varied pre- and post-treatment levels of the pollutant, though all post-treatment levels were below the standard. In all cases great concern was expressed, with no significant differences across scenarios; net benefits, being white, and non-English speaking were linked to lower concern. Relative trust seems a better explanation of different attitudes toward benchmark comparisons than varying levels of knowledge, but both hypotheses have drawbacks that merit further testing. These results imply that people with negative views of industry or government, the ones officials might most wish to reassure, will tend to doubt that regulatory benchmarks offer a valid risk comparison.

Adult↗

PubMed2003

Phylogenetically nested comparisons for testing correlates of species richness: a simulation study of continuous variables.

Explaining the uneven distribution of species among lineages is one of the oldest questions in evolution. Proposed correlations between biological traits and species diversity are routinely tested by making comparisons between phylogenetic sister clades. Several recent studies have used nested sister-clade comparisons to test hypotheses linking continuously varying traits, such as body size, with diversity. Evaluating the findings of these studies is complicated because they differ in the index of species richness difference used, the way in which trait differences were treated, and the statistical tests employed. In this paper, we use simulations to compare the performance of four species richness indices, two choices about the branch lengths used to estimate trait values for internal nodes and two statistical tests under a range of models of clade growth and character evolution. All four indices returned appropriate Type I error rates when the assumptions of the method were met and when branch lengths were set proportional to time. Only two of the indices were robust to the different evolutionary models and to different choices of branch lengths and statistical tests. These robust indices had comparable power under one nonnull scenario. Regression through the origin was consistently more powerful than the t-test, and the choice of branch lengths exerts a strong effect on both the validity and power. In the light of our simulations, we re-evaluate the findings of those who have previously used nested comparisons in the context of species richness. We provide a set of simple guidelines to maximize the performance of phylogenetically nested comparisons in tests of putative correlates of species richness.

Phylogeny↗

PubMed2006

A model-based approach to treatment comparison in acute migraine.

AIMS: Currently, direct comparisons between 5-HT(1B/d) receptor agonists are used to assess differences and similarities in antimigraine response. Such comparisons depend on the selected sampling time and do not allow evaluation of entire response profiles. A thorough evaluation of drug properties requires that the time course of the response be taken into account. In this investigation we show the advantages of a model-based approach to compare the efficacy of two triptans (sumatriptan vs. naratriptan). METHODS: A Markov model was used to describe the course of a migraine attack over three clinically identified stages. Drug effects were modelled as concentration-dependent increases in transition rates and were parameterised as potency (EC(50)) and maximum effect (E(max)). Parameters were estimated using headache measurements from efficacy studies. Model estimates were then used to compare the pharmacodynamics of the two drugs in a time-independent manner. RESULTS: Efficacy parameters could be derived, allowing for comparison between compounds. The potency ratio (EC50(suma)/EC50(nara)) for headache relief was 3.3 (0.9, 12). The ratio of maximum effects (Emax(suma)/Emax(nara)) for this endpoint was 0.74 (0.55, 0.97). To interpret these efficacy measures and explore their value for the development of antimigraine drugs, results were evaluated against the reported in vitro potency at 5-HT(1B) and 5-HT(1D) receptors. CONCLUSIONS: Comparison of the effects of two or more drugs based on preset sampling times does not allow proper assessment of the antimigraine properties in vivo. Disease dynamics must be considered to evaluate treatment response adequately and optimise the dosing regimen in migraine.

Dose-Response Relationship, Drug↗

PubMed2004

Estimating admixture proportions with microsatellites: comparison of methods based on simulated data.

Several methods have been developed to estimate the parental contributions in the genetic pool of an admixed population. Some pair-comparisons have been performed on real data but, to date, no systematic comparison of a large number of methods has been attempted. In this study, we performed a simulated data-based comparison of six of the most cited methods in the literature of the last 20 years. Five of these methods use allele frequencies and differ in the statistical treatment of the data. The last one also considers the degree of molecular divergence by estimating the coalescence times. Comparisons are based on the frequency at which the method can be applied, the bias and the mean square error of the estimation, and the frequency at which the true value is within the confidence interval. Eventually, each method was applied to a real data set of variously introgressed honeybee populations. In optimal conditions (highly differentiated parental populations, recent hybridization event), all methods perform equally well. When conditions are not optimal, the methods perform differently, but no method is always better or worse than all others. Some guidelines are given for the choice of the method.

Animals↗

PubMed1994

Comparison between Fastpac and conventional Humphrey perimetry.

As part of the Melbourne Visual Impairment Project, a substudy was performed to determine the efficacy of the newly released Fastpac program for the Humphrey Field Analyser. A comparison was performed of the Fastpac and conventional full threshold 24-2 fields obtained in 39 eyes of 36 participants. Also a comparison study was performed of the standard and non-standard 80-point screening tests to the standard 24-2 full threshold test in 23 eyes of 23 participants. In the full threshold comparison there was 100% agreement between the two with Fastpac being 32% to 39% faster than standard. In the 80-point screening test comparison, non-standard was no faster than standard. Sensitivities were 17/17 (1.0) for non-standard and 15/18 (0.83) for standard, as compared with the standard 24-2 full threshold test. Fastpac software offers accurate screening and threshold testing in less time than the standard algorithm.

Algorithms↗

PubMed2006

Efficacy and tolerability of a new synergized pyrethrins thermofobic foam in comparison with benzyl benzoate in the treatment of scabies in convicts: the ISAC study (Studio Della scabbia in ambiente carcerario).

BACKGROUND: Scabies is a very common skin infection in convicts. The SIMSPE Society (Società Italiana di Medicina e Sanità Penitenziaria) has organized and conducted a multicentre, randomized, comparative, parallel group, investigator-blinded trial to evaluate the efficacy and tolerability of synergized pyrethrins foam (PF) in comparison with benzyl benzoate (BB) lotion. METHODS: A total of 240 convicted patients, enrolled in eight National Jail Institutions, with a clinical diagnosis of scabies, were treated with PF (n = 120) for three consecutive days or BB (n = 120) for five consecutive days. Primary study endpoints were the clinical cure rate and the local tolerability. Secondary endpoints were clinical evolution of scabietic lesions and itching intensity. Study outcomes were assessed using appropriate semiquantitative scores at baseline and after 2 and 4 weeks. A second treatment cycle was applied if after 2 weeks the patient was not judged clinically cured. RESULTS: At week 2, a total of 75% (95% CI: 66-82%) and 71% (95% CI: 62-78%) of patients showed a complete clinical cure rate in the PF and BB groups, respectively. At week 4, the percentage of totally cured patients increased up to 95% (95% CI: 89-97%) and 91% (95% CI: 83-94%) in the PF and BB groups, respectively (P = NS between groups). At week 4, 5% in the PF group and 9% in the BB group complained of itching. Burning and irritation after treatment applications were more common in the BB group in comparison with the PF group. The tolerability score was better in the PF group in comparison with to BB group (2.9 vs. 2.2; P = 0.0001). A total of 95% of patients in the PV group had a good tolerability score (i.e. = 3) in comparison with 41% in the BB group. CONCLUSION: Our results show that a 3-day treatment with pyrethrins thermofobic foam is at least as effective as a 5-day treatment with benzyl benzoate lotion in convicted subjects with scabies. The foam formulation is better tolerated than the benzyl benzoate lotion.

Administration, Topical↗

PubMed1997

The role of comparison questions in physiological detection of deception.

Comparison questions in physiological detection of deception were studied with 60 "guilty" and 60 "innocent" participants in a mock crime experiment. Different types of comparison questions were used in four conditions: relevant-irrelevant (R-I) participants answered only relevant and neutral questions; trivial directed lie participants were instructed to lie to three of the six neutral questions; personal directed lie participants were instructed to lie to personally relevant questions; and probable lie participants received traditional probable lie comparison questions. Respiration, cardiovascular, vasomotor, and electrodermal activity were recorded. Manipulation of the comparison questions produced different patterns of physiological responses for innocent but not for guilty participants. The R-I test produced an unacceptable rate of false positive decisions.

Adolescent↗

PubMedDate not supplied

Eliciting stated preferences for health-technology adoption criteria using paired comparisons and recommendation judgments.

OBJECTIVES: The principal aim of this study was to illustrate applying discrete-choice methods for eliciting preferences for technology adoption criteria, including threshold values for cost-effectiveness ratios. A secondary objective was to compare the criteria weights of a sample of industry stakeholders with the results obtained from a study of National Institute for Health and Clinical Excellence (NICE) recommendations. METHODS: We administered a two-stage stated-preference (SP) question format to a sample of respondents who have expertise in applying economic analysis to technology adoption decisions. We elicited paired comparisons and recommendation judgments for similar criteria from a sample of International Society for Pharmacoeconomics and Outcomes Research members. Respondents evaluated nine pairs of hypothetical drugs, first indicating which drug was "better," then indicating what they would recommend to a reimbursement authority such as the National Health Service. Stated-choice studies often obtain only paired-comparison judgments. RESULTS: Parameter estimates from the initial paired-comparison question indicate only incremental cost-effectiveness ratio and number of affected patients influence evaluations. These two factors have identical weights in the second recommendation question, but all four factors were considered in determining the recommendation threshold. Our sample was more willing than NICE to accept trade-offs between cost-effectiveness and other drug features and was less concerned about cost-effectiveness ratios and information uncertainty. Nevertheless, our sample was in agreement with NICE about the importance of the number of patients who would benefit as a criterion for influencing adoption recommendations. CONCLUSION: This study demonstrates that including a question allowing respondents the opportunity to reject both alternatives in a forced-choice paired comparison can be important for obtaining accurate preference estimates. Our results demonstrate that SP methods offer a feasible means of quantifying a broad set of valuations that incorporate the preferences of patient, citizen, payer, and other stakeholder groups.

Academies and Institutes↗

PubMed2005

Combining multiple comparisons and modeling techniques in dose-response studies.

The analysis of data from dose-response studies has long been divided according to two major strategies: multiple comparison procedures and model-based approaches. Model-based approaches assume a functional relationship between the response and the dose, taken as a quantitative factor, according to a prespecified parametric model. The fitted model is then used to estimate an adequate dose to achieve a desired response but the validity of its conclusions will highly depend on the correct choice of the a priori unknown dose-response model. Multiple comparison procedures regard the dose as a qualitative factor and make very few, if any, assumptions about the underlying dose-response model. The primary goal is often to identify the minimum effective dose that is statistically significant and produces a relevant biological effect. One approach is to evaluate the significance of contrasts between different dose levels, while preserving the family-wise error rate. Such procedures are relatively robust but inference is confined to the selection of the target dose among the dose levels under investigation. We describe a unified strategy to the analysis of data from dose-response studies which combines multiple comparison and modeling techniques. We assume the existence of several candidate parametric models and use multiple comparison techniques to choose the one most likely to represent the true underlying dose-response curve, while preserving the family-wise error rate. The selected model is then used to provide inference on adequate doses.

Clinical Trials, Phase II as Topic↗