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J P Matts

Publications and source records attributed to J P Matts.

49 records · Page 3Linked to original sources
PubMed1988

Properties of permuted-block randomization in clinical trials.

This article describes some of the important statistical properties of the commonly used permuted-block design, also known simply as blocked-randomization. Under a permutation model for statistical tests, proper analyses should employ tests that incorporate the blocking used in the randomization. These include the block-stratified Mantel-Haenszel chi-square test for binary data, the blocked analysis of variance F test, and the blocked nonparametric linear rank test. It is common, however, to ignore the blocking in the analysis. For these tests, it is shown that the size of a test obtained from an analysis incorporating the blocking (say T), versus an analysis ignoring the blocking (say TI), is related to the intrablock correlation coefficient (R) as TI = T(1-R). For blocks of common length 2m, the range of R is from -1/(2m-1) to 1. Thus, if there is a positive intrablock correlation, which is more likely than not for m greater than 1, an analysis ignoring blocking will be unduly conservative. Permutation tests are also presented for the case of stratified analyses within one or more subgroups of patients defined post hoc on the basis of a covariate. This provides a basis for the analysis when responses from some patients are assumed to be missing-at-random. An alternative strategy that requires no assumptions is to perform the analysis using only the subset of complete blocks in which no observations are missing. The Blackwell-Hodges model is used to assess the potential for selection bias induced by investigator attempts to guess which treatment is more likely to be assigned to each incoming patient. In an unmasked trial, the permuted-block design provides substantial potential for selection bias in the comparison of treatments due to the predictability of the assignments that is induced by the requirement of balance within blocks. Further, this bias is not eliminated by the use of random block sizes. We also modify the Blackwell-Hodges model to allow for selection bias only when the investigator is able to discern the next assignment with certainty. This type of bias is reduced by the use of random block sizes and is eliminated only if the possible block sizes are unknown to the investigators. Finally, the Efron model for accidental bias is used to assess the potential for bias in the estimation of treatment effects due to covariate imbalances. For the permuted-block design, the variance of this bias approaches that of complete randomization as the half-block length m----infinity.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1988

Randomization in clinical trials: conclusions and recommendations.

The statistical properties of simple (complete) randomization, permuted-block (or simply blocked) randomization, and the urn adaptive biased-coin randomization are summarized. These procedures are contrasted to covariate adaptive procedures such as minimization and to response adaptive procedures such as the play-the-winner rule. General recommendations are offered regarding the use of complete, permuted-block, or urn randomization. In a large double-masked trial, any of these procedures may be acceptable. For a given trial, the relative merits of each procedure should be carefully weighed in relation to the characteristics of the trial. Important considerations are the size of the trial, overall as well as within the smallest subgroup to be employed in a subgroup-specific analysis, whether or not the trial is to be masked, and the resources needed to perform the proper randomization-based permutational analysis.

Clinical Trials as Topic↗
PubMed1988

Predictors of total and low-density lipoprotein cholesterol change after partial ileal bypass.

POSCH is a prospective, randomized secondary intervention trial examining the effect of maximal lipoprotein modification achieved by partial ileal bypass on overall mortality and the course of coronary heart disease. In the initial 189 surgical patients, total cholesterol levels decreased from 256.7 +/- 2.6 mg/dl to 166.6 +/- 2 mg/dl, and low-density lipoprotein cholesterol levels decreased from 181.5 +/- 2.7 mg/dl to 94.1 +/- 1.7 mg/dl 3 months after operation. These significant decreases were sustained through 5 years of follow-up (p less than 0.001). The total cholesterol level was 29.2 +/- 0.9 percent lower and the low-density lipoprotein cholesterol level was 43.2 +/- 1 percent lower at 5 years compared with the baseline level. Decreases of similar magnitude were seen in each of the common WHO lipoprotein phenotypes. The baseline total cholesterol level was the only significant independent preoperative predictor of the 5 year total cholesterol level (correlation coefficient 0.547; p less than 0.001), and the baseline low-density lipoprotein cholesterol level was the only significant independent preoperative determinant of the 5 year low-density lipoprotein cholesterol level (correlation coefficient 0.599; p less than 0.001). These relationships are expressed by the following equations: 5 year total cholesterol = 0.54 X baseline total cholesterol + 42.3, and 5 year low-density lipoprotein cholesterol = 0.455 X baseline low-density lipoprotein cholesterol + 19.2. The decrease in total and low-density lipoprotein cholesterol levels after partial ileal bypass are greater than reported by any trial of drug or diet intervention, including the Lipid Research Clinics Coronary Primary Prevention Trial which examined cholestyramine. Estimation of the change in total and low-density lipoprotein cholesterol levels after partial ileal bypass can be made based on preoperative lipid analysis and is essential in comparing different therapeutic modalities and assessing the role of partial ileal bypass among strategies aimed at lowering coronary heart disease risk.

Adult↗
PubMed1988

Low plasma lipid levels and increased cholesterol synthesis after partial ileal bypass plus lovastatin in hypercholesterolemic rabbits.

Partial ileal bypass (PIB) lowers the plasma total cholesterol (C) level, thereby increasing hepatic C synthesis to replenish bile acid and C stores. Lovastatin, a C synthesis inhibitor, may act as a potential adjuvant to PIB for lipid lowering. In this study, the effects of PIB and lovastatin, alone and in combination, were examined in plasma and tissue. For 14 weeks, 32 New Zealand White rabbits received a C-free, alfalfa-free, natural-ingredients diet previously shown to induce hypercholesterolemia. The rabbits were divided into control, lovastatin, PIB, and PIB plus lovastatin groups. Lovastatin was administered at a dose of 0.35 mg/kg twice daily. Compared with the control group, PIB alone decreased the plasma total C level by 75% (p less than 0.005), the low-density lipoprotein (LDL)-C level by 79% (p less than 0.025), and hepatic C content by 50% (p less than 0.05), while increasing hepatic C synthesis by 176% (p less than 0.05). Compared with the control group, lovastatin alone decreased the plasma total C value by 36% (p = NS), the LDL-C level by 35% (p = NS), hepatic C content by 29% (p = NS), and hepatic C synthesis by 52% (p = NS). Compared with the control group, the combination of PIB and lovastatin decreased the plasma total C level by 78% (p less than 0.005), the LDL-C level by 74% (p less than 0.025), and hepatic C content by 58% (p less than 0.05); however, the hepatic C synthesis increased by 490% (p less than 0.005) compared with the control group and by 110% (p less than 0.05) compared with PIB alone. This is the first demonstration of a metabolic reversal of the cholesterol synthesis inhibition engendered by lovastatin. We conclude that both PIB and lovastatin lower plasma total C and lipoprotein C fractions. Their combination has an additive C-lowering effect in plasma and decreases tissue C content by increasing cellular C demand. This latter effect overcomes the inhibitory effect of lovastatin on hepatic C synthesis, resulting in an augmented compensatory increase in hepatic C synthesis.

Animals↗
PubMed1987

Program on Surgical Control of the Hyperlipidemias (POSCH): recruitment experience.

The Program on Surgical Control of the Hyperlipidemias (POSCH) is an investigator-initiated NHLBI grant-funded secondary coronary heart disease intervention trial using partial ileal bypass (PIB) for lipid reduction. Randomization started in September 1975 and ended in July 1983 with enrollment of 838 participants (421 surgery, 417 controls). The trial is scheduled to reveal the atherosclerosis impact of the lipid changes in 1990, at which time the average individual in the program will have been followed for 9.6 years. Initially, the magnitude of the recruitment task was greatly underestimated. An area containing 500,000 people was judged to be sufficient to randomize one patient per month. Actually, a population of 2.4-10.5 million, depending upon proximity to a clinic, was needed to achieve this goal. The study design was changed in 1981, due to recruitment costs, with reduction of the number of individuals to be randomized from 1000 to 838 and with extension of the duration of minimum follow-up from 5 to 7 years. Only with the development of a uniform model clinic concept, with specified levels of performance calculated from actual recruitment data, did accrual of patients into the trial become predictable and achievable. Some of the recruitment delays in POSCH were related to problems, in part generic to the existent grant funding mechanism and associated with decisions made by NHLBI and its Advisory Council. These delays were manifested by denial of reallocation of approved funds to initiate replacement clinics for discontinued ones, an 18-month delay in implementation of a protocol change in lipid criteria suggested by the Data Monitoring Committee, and a 2-year delay in the starting date for the fourth active clinic.

Adult↗
PubMed1987

An example of expert systems applied to clinical trials: analysis of serial graded exercise ECG test data.

Clinical trials collect large amounts of data over time. The use of statistical methods to compare and interpret these serial data often fall short of complete evaluation because the analysis requires clinical judgment. As an alternative, some trials use individual experts or panels of experts to evaluate data, but this method usually requires the participation of clinicians who must spend large amounts of time performing tedious, repetitive tasks. The authors examined the use of expert systems to analyze serial clinical trial data where the analyses required use of clinical judgment. A prototype expert system was built to assess the data obtained from a pair of serial graded exercise ECG tests and reach a decision that would duplicate the decision reached by a cardiologist. The experiment was successful. Expert systems should be further developed and tested in other areas, such as serial coronary arteriography data.

Clinical Trials as Topic↗
PubMed1987

Lipoprotein modification achieved by partial ileal bypass: five-year results of The Program on the Surgical Control of the Hyperlipidemias.

The Program on the Surgical Control of Hyperlipidemias (POSCH) is a multicentered, randomized, secondary intervention trial assessing the effect of lipoprotein modification achieved by partial ileal bypass (PIB) on overall mortality rates and the course of coronary heart disease. Of the 838 participants, 396 (196 control and 200 surgical patients) have complete 5-year lipoprotein results and are the basis of this report. After PIB, total cholesterol level decreased 24 +/- 1.2% (mean +/- SEM) and low-density lipoprotein cholesterol level fell 38 +/- 1.5% in comparison with control subjects. High-density lipoprotein (HDL) cholesterol level was not changed by PIB; however, a significant decrease in HDL occurred over 5 years in the control group (41.7 +/- 0.7 mg/dl versus 39.5 +/- 0.6 mg/dl, p less than 0.05). This led to consistently higher HDL levels in the surgical group in comparison with control subjects after PIB. Very low-density lipoprotein cholesterol and triglyceride levels were higher in the surgery group than in control subjects (24 +/- 7.6% and 21 +/- 5.4% at 5 years). Apolipoprotein B-100 was significantly lower, and apolipoprotein A-I and HDL-2 were significantly higher in the surgery group. These lipoprotein changes are greater than have been reported from any previous trial of dietary or pharmacologic intervention, including the Lipid Research Clinics-Coronary Primary Prevention Trial, which used cholestyramine. Based on available epidemiologic data, these changes predict a marked reduction in morbidity and mortality rates associated with coronary heart disease after PIB.

Adult↗
PubMed1987

Synergistic lipid-lowering effects of alfalfa meal as an adjuvant to the partial ileal bypass operation.

Partial ileal bypass (PIB) and ingestion of alfalfa are both known to lower plasma cholesterol (C) levels. During an 18-week period, the combined effects of both were studied in four randomized groups of rabbits receiving C-free, hypercholesterolemia-inducing, semisynthetic diets 3 weeks after sham or PIB surgery. The diets, with or without alfalfa, had similar overall compositions of fat, protein, carbohydrate, and fiber. We measured blood C, triglycerides (T), and lipoprotein fractions of both C and T at biweekly intervals. In vivo liver and small-bowel synthesis of C, fatty acids (FA), and nonsaponifiable lipids (NSL) were determined with radioactive 14C-acetate at the end of the study. The results were evaluated by means of analysis of variance using unweighted cell means. The combined PIB and alfalfa modalities significantly lower C levels in serum, plasma, low-density lipoproteins, and high-density lipoproteins by 66%, 71%, 85%, and 35%, respectively. However, due to alfalfa, a significant increase of 49% was observed in plasma T when both treatments were combined. Liver FA synthesis was significantly decreased (65%) with PIB and increased (161%) with alfalfa; when the two treatments are combined, a nonsignificant response was observed. Similarly, this inverse relationship for PIB and alfalfa was seen for C and NSL synthesis. Small-bowel FA synthesis was significantly decreased (72%) by the combination of PIB and alfalfa. We conclude that alfalfa suppresses, in part, the physiologic rebound effect of PIB surgery by increasing hepatic C and NSL synthesis; inversely, PIB surgery inhibits the additive effect in the liver synthesis of FA produced by alfalfa. Alfalfa and PIB alone, and synergistically, decrease total small-bowel lipid synthesis, specifically that of FA. Alfalfa is an effective adjuvant to PIB for reducing total and lipoprotein C fractions.

Analysis of Variance↗
PubMed1982

The Program on the Surgical Control of the Hyperlipidemias: a status report.

The Program on Surgical Control of the Hyperlipidemias (POSCH) is a multicentered secondary coronary heart disease intervention trial utilizing maximal plasma lipid reduction as achieved by the partial ileal bypass operation. With over 500 patients recruited into this trial at present, the 4-year sequential lipid changes are statistically highly significant and include an approximate 30% plasma total cholesterol and 40% low density lipoprotein (LDL)-cholesterol reduction, with a slight increase in the high density lipoprotein (HDL)-cholesterol and a marked increase in the HDL-cholesterol:LDL-cholesterol ratio of about 75% or higher. A definitive answer to the lipid-atherosclerosis theory corollary--whether a decrease in the plasma cholesterol engenders a reduction in the incidence or severity of atherosclerotic cardiovascular disease--can be expected from these marked lipid changes in POSCH.

Adult↗
PubMed1980

The POSCH Information Management System: experience with alternative approaches.

An unconventional approach to the information management system for a clinical trial is presented in this paper: employment of a large shared computer utility, use of existing packaged software, and use of a generalized data base management system. An easily maintained system was developed at a very economical cost. The paper is designed to present our experiences and include descriptions of a series of problems that were faced and solved: design problems, problems with error corrections, and problems unique to our operational procedures. The good results are due as much to careful management as to the initial decision to use the unconventional approach. Special attention has been paid to cost controls, patient safety, and data security. The approach has been successful, and others are encouraged to consider a similar approach.

Clinical Trials as Topic↗
PubMed1979

Plasma lipoproteins and coronary arteriography in subjects in the program on the surgical control of the hyperlipidemias. Preliminary report.

Coronary arteriographic findings, plasma lipid and lipoprotein levels, and cigarette smoking history are reported for the first 101 male post myocardial infarction survivors who have been entered into the POSCH clinical trial. Estimates of the extent of stenosis in the major coronary arteries were made using 4 models ranging from a simple determination of the number of the 3 major vessels having significant (i.e. 50% or greater stenosis) disease to more complex methods of determining overall extent of disease in 14 major segments of the coronary arteries. Age was shown to be an important factor in the extent of vessel disease. When controlling for age, plasma cholesterol and LDL-cholesterol levels were shown to be related to the extent of disease, especially in Type II hyperlipoproteinemia subjects. Multiple linear regression analysis demonstrated that age and LDL-cholesterol had positive associations and HDL-cholesterol had an inverse association with the coronary artery disease indices. In this comparatively "healthy" subgroup of the overall population of first MI survivors the major CHD risk factors are limited to plasma lipids and cigarette smoking. This preliminary report of 10% of the recruitment objective of the project supports the currently held views of the lipid--atherosclerosis hypothesis regarding the effects of age-total plasma cholesterol, LDL--cholesterol, and HDL--cholesterol on the extent of coronary atherosclerotic plaques, as determined by coronary arteriography.

Adult↗