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Biomedical subjects

C B Begg

Publications and source records attributed to C B Begg.

At least 73 records · Page 4Linked to original sources
PubMed1987

Cancer clinical trials in the USA: patient eligibility, generalizability of results and technology transfer.

The impact of changes in the source population of patients for cancer clinical trials in the USA is considered. The first change, which has already taken place, is the recent trend of including patients treated of community hospitals in cooperative group and other randomized trials. This change was designed to augment accrual to studies, and to disseminate state-of-the-art information on patient care. The change has been shown to be a successful one, with community hospitals providing high quality participation in the trials. In addition, the research protocols have been seen to influence the care of many patients treated off-protocol. The inclusion of community hospitals in the trials clarifies our understanding of the generalizability of the results of the trials. The issue of generalizability is, however, obscured by the fact that the great majority of cancer patients are not treated on protocols. Indeed most of them are ineligible for protocols. The rationale for strict eligibility is unclear in many cases, and its use greatly reduces accrual and casts doubt on the generalizability of results. In the future, more care should be paid to the selection of the source population for clinical trials.

Clinical Trials as Topic↗
PubMed1987

Prolonged unmaintained remission after intensive consolidation therapy in adult acute nonlymphocytic leukemia.

Thirty-five adults with acute nonlymphocytic leukemia who were in complete remission after initial induction therapy received a single course of high-dose cytarabine and amsacrine as consolidation therapy. No further therapy was administered. Despite substantial toxicity, the median duration of disease-free survival was 12 months, and 30% of patients are projected to be alive in continuous complete remission at 3 years. A single course of intensive postremission chemotherapy provides long-term disease-free survival in the absence of any further treatment.

Acute Disease↗
PubMed1986

The use of ambulatory testing in prepaid and fee-for-service group practices. Relation to perceived profitability.

To examine the influence of method of payment on ambulatory testing by internists, we compared the rate at which patients with uncomplicated hypertension were tested by 10 doctors practicing in large fee-for-service groups with that by 17 doctors in large prepaid groups. We examined the use of individual tests and asked the doctors in the fee-for-service groups what they believed about the profitability and costs of tests. After correcting for the patient's age, sex, duration of disease, and severity of disease as measured by pretreatment blood pressure, and for the doctor's year of medical school graduation, we found that 50 percent more electrocardiograms were obtained among patients in fee-for-service practices (0.69 per patient per year vs. 0.45, P = 0.006), and 40 percent more chest radiographs (0.49 vs. 0.35, P = 0.11). Fee-for-service doctors believed that both tests were associated with high profit and costs. These results suggest that the use of certain high-profit, high-cost tests is higher in large fee-for-service groups than in large prepaid groups. Although the generalizability of conclusions based on this limited study must be considered tentative, the findings suggest that it may be appropriate to consider changing the payments for tests as part of a more general reform of the fee schedules.

Ambulatory Care↗
PubMed1986

The influence of uninterpretability on the assessment of diagnostic tests.

A frequent problem faced by physicians utilizing diagnostic tests is the occurrence of uninterpretable test results. Such results, if they occur commonly, can seriously impair the diagnostic performance of the test. Moreover, in assessing the characteristics of the test, i.e. sensitivity, specificity, etc. failure to consider the impact of uninterpretability will artificially inflate the test characteristics. In this paper we explore the implications of this issue. We observe that a relevant factor is the potential repeatability of the test, i.e. whether the cause of uninterpretability is a transient phenomenon or an inherent property of the subject. We distinguish uninterpretable results, in which no result is obtained, from indeterminate results, in which the result is equivocal, or for which predisposing concomitant factors limit the interpretability of the result. Our results demonstrate that the naive approach of ignoring uninterpretable results in test assessments may indeed be unbiased in certain circumstances. However, if the cause of uninterpretability is related to disease status or to the potentially observable test result, then this approach will lead to bias. In either case, the frequency of uninterpretability is an important consideration in the cost-effectiveness of the test.

Bayes Theorem↗
PubMed1986

Statistical methods in medical diagnosis.

A review of statistical methods in medical diagnosis is presented. Research has focused on three distinct tasks: classification of subjects into probable diagnostic categories on the basis of presenting clinical indicators (discriminant analysis), assessment of diagnostic test characteristics, and relation of diagnostic testing to subsequent patient management. Although many sophisticated models have been developed for discriminant analysis, recent empirical comparisons indicate that standard methods such as linear discrimination and logistic regression work very well. More research is needed to overcome practical difficulties that are not accommodated in the conventional assumptions. Research on the assessment of diagnostic tests has been oriented more toward selection biases and practical problems. There is a need to develop generalized models for the problem of differential diagnosis. The relation of testing to subsequent management of the patient is a topic that has only recently been explored. It represents an important task in the cost-effective management of health resources.

Decision Support Techniques↗
PubMed1985

Probabilistic sensitivity analysis using Monte Carlo simulation. A practical approach.

The data for medical decision analyses are often unreliable. Traditional sensitivity analysis--varying one or more probability or utility estimates from baseline values to see if the optimal strategy changes--is cumbersome if more than two values are allowed to vary concurrently. This paper describes a practical method for probabilistic sensitivity analysis, in which uncertainties in all values are considered simultaneously. The uncertainty in each probability and utility is assumed to possess a probability distribution. For ease of application we have used a parametric model that permits each distribution to be specified by two values: the baseline estimate and a bound (upper or lower) of the 95 percent confidence interval. Following multiple simulations of the decision tree in which each probability and utility is randomly assigned a value within its distribution, the following results are recorded: (a) the mean and standard deviation of the expected utility of each strategy; (b) the frequency with which each strategy is optimal; (c) the frequency with which each strategy "buys" or "costs" a specified amount of utility relative to the remaining strategies. As illustrated by an application to a previously published decision analysis, this technique is easy to use and can be a valuable addition to the armamentarium of the decision analyst.

Decision Making↗
PubMed1985

Assessment of diagnostic technologies. Methodology for unbiased estimation from samples of selectively verified patients.

Concern with the efficacy of diagnostic technologies has stimulated numerous studies aimed at quantifying the discriminatory properties of various tests and procedures. These have focused principally on estimations of the result conditional probabilities, given disease status, eg, the sensitivity and specificity or the ROC curve. A source of bias in estimating these probabilities that is often unavoidable is created by the existence of a nonrandom selection mechanism for determining which patients initially tested will receive definitive verification of disease status. Correction for verification bias requires frequency data on the test results and any symptoms or other factors that influence selection for verification, both in the verified sample and in the source sample of patients tested.

Evaluation Studies as Topic↗
PubMed1984

Patient-oriented performance measures of diagnostic tests. 1. Tools for prospective evaluation of test order decisions.

Prospective assessment of a test for possible use in evaluation of a patient ideally should be based on the test's ability to affect subsequent patient management beneficially, in relation to both the costs of the test itself and the costs of misclassification of disease status. This requires specification of the costs and benefits of subsequent actions and the cost of the test, estimation of the probability of disease, knowledge of the discriminatory properties of the test, and formal decision analysis. Often, however, the physician has less complete information with which to make a test order decision. A spectrum of performance measures exists for characterising a diagnostic test, ranging from measures that are largely patient-independent to measures that are highly patient-dependent. Two measures from the patient-dependent part of the spectrum, Assignment Potential and Assignment Strength, can be useful in decision making when formal decision analysis is not feasible. A third measure, the U-Factor, is the product of the other two, and is a computational tool that facilitates formal decision analysis.

Diagnosis↗
PubMed1984

Patient-oriented performance measures of diagnostic tests. 2. Assignment potential and assignment strength.

Assignment Potential (AP) is a performance measure of a diagnostic test, characterizing the chance that, as a consequence of performing the test, the probability of disease will exceed a decision threshold, thereby permitting a management action to be taken. Another performance measure, Assignment Strength (AS) characterizes the average extent to which a decision threshold will be exceeded when the post-test probability of disease does exceed the threshold. Both AP and AS are functions of prior probability of disease and decision threshold, and can be represented as two-dimensional contour maps indicating their behavior throughout the entire probability and threshold space. AP and AS can be determined for both discrete-valued tests and tests with continuous spectra of results. The contour map displays facilitate determination of the values of these measures at any prior probability and threshold, as well as visual sensitivity analysis for ranges of prior probability and/or threshold. AP and AS may be useful to the clinician in prospective evaluation of a diagnostic test in situations where formal decision analysis is not feasible.

Diagnosis↗
PubMed1984

Patient-oriented performance measures of diagnostic tests. 3. U-Factor.

When a clinician is faced with the problem of deciding whether to order a specific diagnostic test, the ideal information would be the utility of the "perform test" branch of the decision tree versus the utility of the "do not perform test" branch. This difference in utility is termed the Expected Utility of the Test ( EUT ). We propose a new performance measure of a test called the U-Factor (UF) which is related to EUT by a simple formula. UF depends on the prior probability of disease and on the decision thresholds at which one would be indifferent between any two immediately subsequent management options, and can be presented as a two-dimensional nomogram. UF is useful as a computational aid in a formal decision analysis, and may be useful as an informal measure of the value of a diagnostic test when a formal analysis is not feasible.

Costs and Cost Analysis↗
PubMed1984

Construction of receiver operating characteristic curves when disease verification is subject to selection bias.

The estimates of ROC curves, which are frequently used in the assessment of diagnostic tests, may be biased if the sample is restricted to subjects whose disease status has been definitively verified. A method to provide an unbiased estimate of the ROC curve under these sample conditions is proposed. The new method requires information on the probability distribution of test results in the population from which the verified sample is drawn. It is illustrated using data from a study of computed tomography for fever of uncertain origin.

Diagnosis↗
PubMed1984

A critical comparison of allogeneic bone marrow transplantation and conventional chemotherapy as treatment for acute nonlymphocytic leukemia.

Published data from two centers conducting bone marrow transplantation on patients with acute nonlymphocytic leukemia in first remission were pooled and compared with results from an Eastern Cooperative Oncology Group (ECOG) study in which patients were treated with conventional chemotherapy. A series of adjustments were made to the ECOG sample to account for selection factors that restrict access of patients to transplantation. The transplant sample exhibits considerably higher disease-free survival when compared to the adjusted ECOG series (53% versus 21% at three years). The transplant series is somewhat younger than the ECOG series (median, 24 years versus 28 years). The impact of age on the disease-free survival results is difficult to assess because of the relatively small samples in the different age groups. However, by defining a suitable control group, methodology for making a critical comparison between the two modalities is presented which, if applied to larger samples of patients, should help to resolve the issue. In the absence of data from a large, prospective randomized study, a critical retrospective comparison of available data is essential in the assessment of treatment options.

Acute Disease↗
PubMed1984

Full dose versus attenuated dose daunorubicin, cytosine arabinoside, and 6-thioguanine in the treatment of acute nonlymphocytic leukemia in the elderly.

Between July 1, 1981 and November 1, 1982, 45 patients with acute nonlymphocytic leukemia (age, greater than or equal to 70 years) were randomly assigned to receive induction chemotherapy using either daunorubicin, cytosine arabinoside, and 6-thioguanine in full dosage (F DAT) or an attenuated schedule of the same drugs (At DAT) as part of an Eastern Cooperative Oncology Group controlled trial. Forty patients were deemed evaluable, 20 on each arm. The overall complete remission (CR) rate for all patients in both arms was 28% (11/40). There was no significant difference in CR rates between the two arms. There were 12 early deaths (less than 60 days) in the F DAT arm compared with only five early deaths on the At DAT arm (P = .05). Due primarily to this early death rate, the median survival for the F DAT group was 29 days v 159 days for the At DAT groups (P = .02). The range of survival of the patients in CR for the At DAT group given either one or two cycles of induction therapy was 121 to 414 days, while the survival range for the F DAT CR patients was 121-186 + days. The median survival for those not achieving CR was 14 days for the F DAT group v 80 days for the At DAT (P less than .02). Fifty-nine percent of the At DAT patients spent greater than 100 days out of the hospital v 12% for the F DAT group. Attenuated chemotherapy with lower doses of DAT is the preferred induction regimen for elderly patients with acute nonlymphocytic leukemia since it causes fewer early deaths, allows a better quality of life, and yields survival times as durable as intensive therapy.

Acute Disease↗
PubMed1984

The effects of physicians' training and personality on test ordering for ambulatory patients.

We studied records of 351 hypertensive patients cared for by 30 internists in private office practice. We correlated the use of outpatient diagnostic tests with personal characteristics of the prescribing physicians. Doctors trained in medical schools with academic orientations used more tests than other physicians. Patterns of use were not strongly related to the number of years since medical school graduation, or physicians "intolerance of ambiguity" as measured by a standard psychological instrument. These findings suggest that certain types of training may predispose physicians to be high testers.

Adult↗
PubMed1984

Treatment allocation for nonlinear models in clinical trials: the logistic model.

Many clinical trials have a binary outcome variable. If covariate adjustment is necessary in the analysis, the logistic-regression model is frequently used. Optimal designs for allocating treatments for this model, or for any nonlinear or heteroscedastic model, are generally unbalanced with regard to overall treatment totals and totals within strata. However, all treatment-allocation methods that have been recommended for clinical trials in the literature are designed to balance treatments within strata, either directly or asymptotically. In this paper, the efficiencies of balanced sequential allocation schemes are measured relative to sequential Ds-optimal designs for the logistic model, using as examples completed trials conducted by the Eastern Cooperative Oncology Group and systematic simulations. The results demonstrate that stratified, balanced designs are quite efficient, in general. However, complete randomization is frequently inefficient, and will occasionally result in a trial that is very inefficient.

Biometry↗
PubMed1984

A randomized study of the efficacy of consolidation therapy in adult acute nonlymphocytic leukemia.

The Eastern Cooperative Oncology Group conducted a randomized study to determine the efficacy of consolidation therapy in prolonging the duration of complete remission (CR) in adults with acute nonlymphocytic leukemia (ANLL). Induction chemotherapy with daunorubicin, cytosine arabinoside, and 6-thioguanine (DAT) yielded CR in 65% of 283 patients with ANLL, aged 16-69. For patients aged 60-69, the CR rate was 58%. Of 184 patients in CR, 146 patients were then randomized to receive either maintenance therapy with weekly cytosine arabinoside and 6-thioguanine alone (69 patients) or two courses of reduced doses of DAT 1 mo apart, before commencing the same maintenance program (77 patients). Consolidation therapy resulted in hematologic toxicity, but was not lethal in any of the eligible patients. Patients receiving consolidation plus maintenance therapy experienced a longer CR duration (40 wk) and disease-free survival at 2 yr (28%) than did those patients receiving maintenance therapy alone (34 wk and 14%, respectively). These differences are not statistically significant. These results suggest that approaches to consolidation therapy employing reduced doses of the induction therapy regimen can have, at best, only a small benefit. For consolidation therapy to provide substantial improvement in CR duration, intensive regimens with non-cross-resistant drugs will be required.

Acute Disease↗
PubMed1983

Adult non-Hodgkin's lymphoma. Correlation of cell surface marker phenotype with prognosis, the new working formulation, and the Rappaport and Lukes-Collins histomorphologic schemes.

The interrelationships between histomorphologic classification, cell surface marker phenotype and prognosis were prospectively studied in 130 adults with non-Hodgkin's lymphomas. Within each of the classification schemes used there were certain histologic variants that exhibited heterogeneity of cell lineage as well as those that were extremely uniform. Diffuse lymphomas with cell populations consisting of large cells, or mixtures of large and small cells were the most heterogeneous phenotypically and were most resistant to precise definition of immunologic cell lineage. The new Working Formulation for Clinical Usage likewise exhibited considerable heterogeneity of phenotype even within well defined histomorphologic categories. Two immunologic phenotypic variables that conferred a significant favorable prognosis were the expression of surface membrane immunoglobulin (B derivation) and the simultaneous expression of a membrane mu and delta immunoglobulin heavy chain. The results of this study suggest that cell surface marker phenotypic determinations have well defined and potentially useful correlations with histomorphologic classification schemes, and are useful in predicting biologic behavior and prognosis. It is suggested that a knowledge of both immunologic phenotype and histomorphologic characteristics is necessary in formulating therapeutic decisions.

Humans↗