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The review is presented in which a great importance of methodology in scientific and practical work of the pathologist is shown. The contents of the notion "methodology" and its levels, methodological developments on the examples from pathological anatomy and its interconnection with other sciences are outlined.
Despite their long history, the number that are in operation now, and the current level of expenditures on them, clinical trials have not been the focus of sufficient methodologic research. The paucity of metholologic explorations is further aggravated by the constraints on communications regarding methodology. Those individuals working in the area of clinical trials need to establish some professional identity with the field. Methodology in the areas of design and management of clinical trials needs to be stimulated, perhaps through special requests for applications (RFAs) and requests for proposals (RFPs). Communications could be improved by the establishments of a professional society, the development of an appropriate journal, and establishment of national training and information centers for clinical trials.
Within the set of measures to protect the marine environment against ever greater viral pollution, the methodology for the detection of human virus in seawater is of primary importance as a means of evaluating the efficiency of protective measures. So far only a limited number of methods have been applied to determine the presence of enteritis virus in sea-water. These methods are the ones already used to study soft water. However, the specific characteristics of sea-water require certain modifications to these methods. Experimental research or on site examinations have to date made significant contribution to the methodology. The importance of the problems posed to hygienists and to health policy makers calls for efforts to perfect these methodologies. The results obtained in this respect, both in the laboratory and in the field, are encouraging. They confirm that the techniques developed are suitable, in the majority of cases, for the detection of enteritis virus in the marine environment, but they still remain to be perfected. The present work takes as its basis both data from the literature and the results of personal experiments.
In an attempt to identify the factors which might affect the measurement of water proton relaxation times in cultured cells, we have begun a long-term study of two human breast cancer cell lines, MDA-MB-231 and MDA-MB-435s. We tested growth rates and cell cycle distribution as intrinsic properties of the cells as well as methodological steps which might affect the measurement of T1 and T2. A detailed examination of the growth rates of the two cell lines, easily recognized as slow (231) and fast (435s) in culture, revealed that this attribute is difficult to correlate precisely with T1s or T2s. The reason is that the relaxation times are necessarily measured at one point in time while the growth rates are a summation of ongoing processes occurring over hours. Cell cycle distribution, on the other hand, can be measured simultaneously with the relaxation times by using cells quick-frozen from the same suspension. By this method, cell cycle distribution appears to be reflected through an effect on T1s. For example, cell pellets distributed 72:15:14 in G0G1:S:G2M has longer T1s (p less than 0.01) than those distributed 43:34:23 in G0G1:S:G2M. Regarding methodological factors, trypsin appeared to lower water content and T2s in the 231 cell line. Drift in the cell cycle distribution after sample preparation did not become significant until after 2 hours in the NMR tube. It was important to standardize the force and duration of centrifugation of the cell pellets to minimize the contribution of the suspending medium without affecting cell viability. We conclude that, given careful control of methodological factors, differences in T1 may reflect metabolic differences as demonstrated by T1 differences in cell pellets showing divergent cell cycle distribution.
The double-blind placebo-comparison randomized clinical trials (RCTs) of cimetidine in the treatment of duodenal ulcer (DU) are examples of good, well-designed clinical trials. With the publication of the first United States RCT in 1978, which reported superiority for cimetidine for only 2 weeks of treatment, grounds for healthy skepticism arose. We undertook a methodologic review of the 16 RCTs published in English through 1980 testing cimetidine in endoscopically documented DU to ascertain if methodologic problems could explain the disparate results. The lack of a clinical classification of disease severity, the failure to consider the additional effect of iatrotherapy (the healing effect of the investigator), the failure to separate duodenitis from ulceration and to note transitions--change in duodenitis and change in ulcer size, and the failure to calculate beta error statistics for "negative" RCTs are important methodologic problems that could explain the disparate results. Future RCTs of therapy in DU should address these issues.
Bile acid production has been measured in 13 studies in 10 hyperlipidemic subjects by simultaneous use of isotope dilution kinetics and chemical balance methodology. When the data of all 13 studies were averaged, the correlation between the two sets of values was negative and weak (r - 0.01, NS). However, when the correlations for normoglyceridemic and hyperglyceridemic subjects were examined separately, a strong positive correlation was found between the values obtained by the two methods in normoglyceridemic subjects (r + 0.92, P less than 0.01) but not in hyperglyceridemic subjects (r - 0.25, NS). Examination of bile acid specific activity decay characteristics in eight studies, where bile was sampled up to six times within the first 24 hr after radio-labeled bile acid infusion, revealed differences in three rate of attainment of peak specific activity and in the time taken subsequently to achieve first order kinetic decay. However, analysis of the data from these eight studies by input-output analysis yielded values for primary bile acid synthesis no different that those generated by conventional isotope dilution kinetics. Thus, bile acid production in normoglyceridemic subjects may be accurately quantitated by either isotope dilution or chemical balance methodology. Our data, as well as results from other laboratories, indicate that the values obtained are strictly comparable. On the other hand, the quantitation of bile acid production in hyperglyceridemic subjects by isotope dilution kinetics gives higher values than those obtained by chemical balance methodology, and in addition, higher values than those obtained in patients with normal plasma triglyceride levels.
To determine whether the findings of case-control studies of risk factors for child abuse may have been biased because of inattention to scientific principles of research design, 22-case-control studies were reviewed investigating either of two risk factors: (1) prematurity or low birth weight of the abused child or (2) young maternal age of the mother of the abused child. Each study was examined to determine compliance with seven methodologic standards that would minimize bias or distortion of the results. No study satisfied all seven standards. Two standards, choice of a specific control group and adjustment for differences in clinical and demographic susceptibility factors, most often affected the results. Studies complying with both of these standards indicated that prematurity or low birth weight is not a risk factor for abuse and that young maternal age at the birth of the abused child is likely to be a risk factor. Few studies complied with the standard concerned with avoidance of detection bias; this failure may have a major effect on the direction bias; this failure may have a major effect on the direction of the results of certain studies. Previous case-control studies of child abuse have important methodologic flaws that can affect the validity of the results. The standards presented should be helpful in planning methodologically rigorous studies.
A simple and practical methodology is proposed to define the "Family Food Basket", that must be based on the prevalent food situation of a country. At present, the "Family Food Basket" is an expression frequently used by government agencies (Ministries of Economics, Agriculture and Statistical Offices), because the money value estimation of the "Basket" is used as the basis for the establishment of minimum wages for the different socioeconomic groups. It is necessary, therefore, to determine the quantities of different foods that should be included as part of the diets so as to cover the nutritional requirements of the population. An explanation is also given here to show the differences between the "Food Basket" and the "Minimum Cost Recommended Diets", prepared in 1970 for the Central American countries. In order to explain the methodology, an example is given trying to define the "Family Food Basket of El Salvador" on the basis of available information gathered from food consumption surveys carried out at national level. Since a standardized methodology to obtain the actual food prices does not exist, some alternatives are given to estimate the money value of the "Family Food Basket".
This article is the first of two parts of a research report on the evolution and magnitude of poverty in Mexico. Herein are presented the methodologies used in both parts and the evolution of poverty. The Poverty Line methodology (PL), in its Standard Basket of Essential Satisfiers version, is succinctly explained. Two problems on the definition of normative requirements are emphasized: the foundations of such requirements and the access route by which needs are to be met (private consumption or public transfers). Identification of six household welfare sources allows for criticism of PL and Unsatisfied Basic Needs methodologies which the Integrated Poverty Measurement Method (IPMM) brings together. IPMM is used to estimate the magnitude of poverty in 1989. The results are presented in the second part of this report. Results analyzed in the last section of this article show that while poverty in Mexico decreased steadily from 77.5% in 1963 to 48.5% in 1981, it increased since 1982, reaching 66% in 1992.
Since the implementation of the 'Huriet law', drugs in phase IV clinical trials are handled by the pharmaceutical Department of the 'Hôpital Neuro-Cardiologique' (Lyon, France). The methodology of these trials is assessed by using a special assessment grid which enables a score for each protocol, with a maximal score of 20 and a minimal one of minus 20. Although many limitations could be advanced, results of this study show that, among 39 assessed trials, 13 trials had weak methodology (score < or = 0), 16 are middle-quality trials (score between 0 and 10) whereas 10 trials only can be considered as having a strong methodology (score > 10). So, a fairly large number of the organized phase IV trials have debatable quality. Moreover, their objective is questionable, that is essentially promotional, in spite of the 'Huriet law' and Persons Protection Committees.
OBJECTIVE: To determine the frequency and temporal changes in application of seven accepted methodological standards for the evaluation of diagnostic tests. DATA SOURCES: A search of the MEDLINE database yielded 1302 articles about diagnostic test studies, during a 16-year secular interval, 1978 through 1993, in four prominent general medical journals. STUDY SELECTION: In the 112 eligible studies, the test was intended for clinical use, indexes of accuracy (sensitivity and specificity or likelihood ratios) were provided, and more than 10 patients were enrolled. DATA EXTRACTION: Although each study was critically reviewed by one primary observer, a subset was independently evaluated for interrater consistency. DATA SYNTHESIS: The percentage of studies that fulfilled criteria for each of the seven methodological standards are as follows: (1) specify spectrum of evaluated patients, 27%; (2) report test indexes for clinical subgroups, 8%; (3) avoid workup bias, 46%; (4) avoid review bias, 38%; (5) provide numerical precision for test indexes, 11%; (6) report frequency and management of indeterminate results when calculating test indexes, 22%; and (7) specify test reproducibility, 23%. Secular increases were found for six of the seven standards in ranges of use from 14% to 31% during 1978-1981 to 1990-1993. Nevertheless, only one standard, avoidance of workup bias, was fulfilled by more than 50% of studies in the most recent secular interval. CONCLUSIONS: These results indicate that most diagnostic tests are still inadequately appraised. The routine demand for methodological standards could raise the quality of diagnostic test information, and the careful predissemination evaluation of diagnostic tests could eliminate useless tests before they receive widespread application.
Between 1989 and 1992, the Agency for Health Care Policy and Research (AHCPR) awarded funding to 14 special projects known as Patient Outcomes Research Teams (PORTs). These large, complex projects form the centerpiece of the first generation of research under the Medical Treatment Effectiveness Program. In carrying out their individual 5-year research plans, and through collaborative work of six Inter-PORT Work Groups, PORTs have contributed to methodological advances related to their specific clinical focus and to outcomes research in general. Each of the PORTs has followed a standard research model, involving the application of: systematic literature review, measurement of outcomes, analysis of cost and claims data, decision analysis, and strategies for disseminating findings. This article reports what has been learned by individual PORTs, and by AHCPR, regarding the usefulness of each of these methodologies, both for the ongoing projects and for the next generation of effectiveness research. Example from individual PORTs and work groups illustrate some of the methodological gains that have been made in effectiveness research and provide a glimpse of the work that remains to be done.
The primary goal of the Inter-PORT work group on Outcomes Assessment is to foster methodological knowledge about the implications of various measure and design decisions for studies of the outcomes of treatment. A number of key methodological issues currently are unresolved and are in need of further study. These include: 1) the best questions to ask to assess how patients are affected by their treatments; 2) the comparative advantages of various study designs, including prospective cohorts, retrospective studies, and randomized clinical trials; 3) the way data collection decisions, such as mode of data collection and use of proxy respondents, affect study results; and 4) the best way to assess the significance of observed effects from patient, provider, and public policy perspectives. Studies conducted by the Patients Outcomes Research Teams (PORTs) are using diverse designs, measures, and data collection procedures. They provide a unique opportunity to further knowledge about methods of obtaining information about treatment outcomes. Through meetings, conferences, and publications, the Inter-PORT work group on Outcomes Assessment is trying to stimulate analyses aimed at methodological issues summarized in this paper and to ensure that new knowledge about methods is disseminated to a wide audience.
The intent of the methodology section of this volume was to provide an overview of recent thinking about analytic techniques that can be used to study chronic care populations, particularly dementia SCUs. As discussed earlier in this article, although not unique to these populations, longitudinal analysis of chronic care populations frequently involves several problems: nonequivalent comparison groups, unbalanced designs, censoring and attrition, autocorrelation (correlated repeated measures) and heterogeneous correlations across repeated measures. The last 5 years has witnessed considerable change and growth in the development of longitudinal modelling methodologies. Although developments in modelling cut across disciplines, there has been a focus on certain types of methods in several fields of applied statistics: psychometrics (e.g., analysis of change, item response theory, Rasch modelling of binary outcomes), mathematical sociology (e.g., structural equation modelling), demography (e.g., transition modelling), epidemiology (e.g., risk modelling), and biostatistics (e.g., examination of intervention effects using marginal and random effects modelling of repeated measures). An important issue is the interrelationship between measurement and outcome assessment. Source of measurement error must be considered (see Zimmerman and Magaziner in this volume), as must bias in assessments (see Teresi and Golden in this volume). While it has long been known that poor measurement can attenuate and bias estimates of longitudinal effects, the answer is not to attempt artificial solutions through use of corrections for attenuation (unreliability). Design and sampling issues are also critical to the correct conduct of any longitudinal study. Otherwise, estimates of prevalence, incidence, and intervention effects will be in error (see Beckett and Evans, in this volume). Several modelling approaches have been reviewed. Different points of view regarding change analysis have been presented; controversy remains regarding the "best" methods for examining change (see the commentary by Rogosa in this volume). Theory building using methods such as structural equation modelling remains a staple of longitudinal analysis, although several caveats have been discussed. New or revisited methodologies (random effects modelling, of which growth curve analysis can be viewed as a special case and event history modelling) offer promise in dealing with the knotty problems inherent in the longitudinal study of chronic care populations, namely, censoring, attrition, and unbalanced designs resulting in missing data (see the commentary by Nesselroade, in this issue). However, it remains clear that no one model or approach will be optimal for all applications.
This bibliography lists all published methodological works (statistical methodology, implementation methodology, review papers, descriptions of software) in the area of population pharmacokinetics/pharmacodynamics up to 1993 and all published works describing applications of population pharmacokinetics/pharmacodynamics up to 1992.
OBJECTIVE: The aim of this study was to assess critically the published literature concerning medical treatment of primary open-angle glaucoma (POAG), and to see whether trial methodologic quality was related to a clinically relevant outcome measure. METHODS: We identified and reviewed the methodologic quality of 102 published randomized clinical trials (RCTs) on treatment of POAG using an explicit protocol and explored the association between selected aspects of design and conduct and the studies' clinical relevance. RESULTS: Our analysis revealed serious methodologic problems with the trials reviewed. Areas of major concern were: use of unsatisfactory or unspecified methods of randomization (89% of the trials reported no information), exclusion of some patients from the analysis (53% of the studies), failure to provide evidence of having estimated the number of patients needed to detect a prespecified treatment difference (96% failed to provide such an estimate), and incomplete description of patient characteristics (in 39% of the RCTs information on this item was insufficient). Within this generally unsatisfactory picture we found, however, that those studies adopting a double-masked design and those not excluding patients after randomization followed patients for longer periods of time and assessed treatment effectiveness using a clinically relevant outcome (that is, visual field changes) compared to other studies. CONCLUSIONS: For clinicians to make use of the results of clinical trials, future studies must be adequately designed and conducted. In particular, proper method of randomization, masking of the observers, and inclusion of all randomized patients in the analysis must be used. Of perhaps even greater importance is the need for trials to measure clinically relevant outcomes.
Although Helen Deutsch's The Psychology of Women contains a wealth of descriptive material about women's problems, the methodology employed by Deutsch in reaching her conclusions about femininity is marred in several ways. Her evolutionary-adaptational bias and natural science approach led to the attribution of questionable biological bases to behavior and to the neglect of social factors and learning. Her concepts and language reveal an unquestioning adoption of Freud's metapsychology and lead to a perception and interpretation of psychological events according to the specific cast of that approach. She confuses her values with definition and observation. A re-examination of the thought of Deutsch seems fitting in these days of ever more extensive reconsideration of the views of Freud and other major psychoanalytic thinkers on the psychology of women. In addition to furthering our understanding of her insights, the study of Deutsch's methodology and its pitfalls contributes to a more critical understanding of the values and preconceptions that influence popular thinking about women and to a deeper grasp of problems inherent in psychoanalytic methodology.
For wheelchair users unable to transfer to a vehicle seat, the wheelchair serves as a means of mobility and postural support during activities of daily living and as a seating support in a vehicle. The performance of commercially available adaptive seating components in a dynamic or impact situation, as well as their effect on the safety of the user, is unknown and should be determined. The main objective of the project was to develop a test methodology to statically determine the crashworthiness of wheelchair headrest systems and show the efficacy of that methodology by applying it to several commercially available headrest systems. The methodology was based on Federal Motor Vehicle Safety Standard (FMVSS) test conditions, which use static test procedures to ensure that vehicle head restraints will perform adequately during actual crash conditions. The procedure developed to evaluate the headrests gave informative and repeatable results. The tests performed calculated the energy associated with a critical deformation of the headrest under quasi-static conditions. The results were used to determine the level of safety provided by the devices and to recommend design improvements. The headrests tested exhibited similar modes of deformation due to bending of a vertical adjustment bar, and several devices were determined to be capable of providing adequate restraint in an impact situation.