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Biomedical subjects

G G Koch

Publications and source records attributed to G G Koch.

At least 19 recordsLinked to original sources
PubMed2006

Are American College of Rheumatology 50% response criteria superior to 20% criteria in distinguishing active aggressive treatment in rheumatoid arthritis clinical trials reported since 1997? A meta-analysis of discriminant capacities.

OBJECTIVE: To carry out a meta-analysis designed to compare the discriminant capacities of American College of Rheumatology 50% (ACR50) with 20% (ACR20) responses in clinical trials on rheumatoid arthritis reported after 1997 and to analyse whether ACR50 can be as informative as ACR20 in distinguishing active from control treatments in more recent trials. METHODS: Clinical trials on rheumatoid arthritis reported since 1997 were identified, which included aggressive combinations of disease-modifying antirheumatic drugs and glucocorticoids, as well as powerful new agents-leflunomide, etanercept, infliximab, anakinra, adalimumab, abatacept, tacrolimus and rituximab. A meta-analysis of ACR20 compared with ACR50 responses for 21 clinical trials was carried out on differences in proportions of responders for active and control treatments and corresponding odds ratios (ORs). RESULTS: In all but one clinical trial on rheumatoid arthritis published since 1997 with data available on ACR20 and ACR50, more than 50% of patients who were ACR20 responders among those randomised to active treatment were also ACR50 responders. This phenomenon was seen for control groups in 38% of trials, many of which included treatment with methotrexate. A meta-analysis of the clinical trials indicated a slight advantage to ACR50 for quantifying treatment comparisons, not significant for differences in proportions but significant for ORs. CONCLUSION: ACR20 and ACR50 seem to be similar in distinguishing active from control treatments in clinical trials on rheumatoid arthritis reported since 1997. As ACR50 represents a considerably stronger clinical response, ACR50 may be a preferred end point for contemporary clinical trials on rheumatoid arthritis.

Antirheumatic Agents↗
PubMed2006

Design of vaccine equivalence/non-inferiority trials with correlated multiple binomial endpoints.

Immunogenicity trials that study the immune responses to vaccination are often used in the vaccine development process as alternatives to clinical efficacy trials. The comparisons of immune responses among various treatment groups are conducted in a non-inferiority or equivalence framework. When there exists a level of immune response that correlates with protection against disease, it is of interest to compare the proportion of responders as defined as response above a specific level or as a predefined increase in immune levels for post-vaccination levels above pre-vaccination levels. Since vaccines often contain several antigens, the correlations between the immune responses need to be taken into account in the analysis. In this paper, we describe appropriate testing methods for demonstrating the non-inferioritylequivalence of two treatments on each of the binomial endpoints. We conduct a comprehensive simulation study to shed light on how the Type I error and power are affected and to what extent when correlated multiple binomial endpoints are present in the vaccine trials. We also illustrate the computation of power for assessment of non-inferioritylequivalence in real studies.

Adolescent↗
PubMed2001

Monitoring a clinical trial with multiple hypotheses concerning the treatment effect on a single primary endpoint.

In a number of clinical trials there is interest in testing more than one hypothesis concerning the treatment effect on a single primary endpoint. For instance, a sponsor of a trial to demonstrate that a test treatment (T) is non-inferior to an active control (R) may also be interested in showing that T is superior to R, if this is the case. Using the closed testing method for constructing tests of multiple hypotheses which control the multiple level of significance, we provide a framework for testing these hypotheses sequentially during a trial at pre-planned interim analyses.

Clinical Trials as Topic↗
PubMed2001

A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee.

OBJECTIVE: To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients with osteoarthritis of the hip or knee. METHODS: Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a score of > or =30 mm on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 microg misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatment regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visual analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety was assessed using a standard form to review adverse events. RESULTS: We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Significantly higher levels of improvement in the primary outcomes were seen for diclofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events were more common when patients took diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as "better" or "much better" by 57% of the 174 patients who provided such ratings for both treatment periods, while acetaminophen was rated as "better" or "much better" by 20% of these patients, and 22% reported no difference (P < 0.001). Differences favoring diclofenac + misoprostol over acetaminophen were greater in patients with more severe osteoarthritis according to baseline pain scores, radiographs, or number of involved joints. CONCLUSION: Patients with osteoarthritis of the hip or knee had significantly greater improvements in pain scores over 6 weeks with diclofenac + misoprostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.

Acetaminophen↗
PubMed2001

Mediation in a family-directed program for prevention of adolescent tobacco and alcohol use.

BACKGROUND: Family Matters is a universal intervention designed to prevent adolescent tobacco and alcohol use through involvement of family members and by targeting family risk factors for tobacco and alcohol use. Previously reported findings suggest that the program reduced the prevalence of both adolescent smoking and drinking in the 12 months after program completion. This paper reports analyses conducted to identify the mediators through which the program influenced adolescent smoking and drinking. METHODS: One thousand fourteen adolescents ages 12 to 14 years and their families, identified by random-digit dialing, were entered into a randomized trial. Adolescents and their parents provided data by telephone for measuring mediator and behavioral variables at baseline, 3 months, and 12 months after program completion. Repeated-measures logistic regression with generalized estimating equations was used to assess mediation processes. RESULTS: The program resulted in statistically significant changes in several substance-specific aspects of the family, such as rule setting about tobacco and alcohol use. However, the intermediate family effects did not account for the program effects on adolescent behavior. CONCLUSIONS: The variables hypothesized to explain program effects were not identified by direct empirical examination.

Adolescent↗
PubMed2001

Prediction of cardiac mortality after myocardial infarction: the role of maximal treadmill stress echocardiography.

Patients frequently undergo low-level exercise treadmill testing after acute myocardial infarction (MI) and, in the absence of inducible ischemia, a maximal test several weeks later. This study examines 203 patients who had 2-dimensional echocardiography before and after a maximal Bruce protocol exercise treadmill test performed 4 to 6 weeks after MI. The subjects were followed for a mean of 43 months (range 1 to 77 months). Predictors of cardiac mortality by multivariate or univariate analysis included an ejection fraction < or =40%, diabetes, age > or=70 years, and ischemia by exercise echocardiography but not by electrocardiography. Therefore, standard electrocardiographic monitoring during exercise treadmill testing 6 weeks after MI fails to predict cardiac mortality. The addition of pre-exercise and post-exercise treadmill stress echocardiography to readily available clinical parameters identifies those patients at greatest risk for cardiac death (resting ejection fraction < or=40%) and detects residual exercise-induced ischemia that may be of additional prognostic value.

Aged↗
PubMed2001

Effect of vaccination by community pharmacists among adult prescription recipients.

BACKGROUND: Millions of doses of influenza vaccine are administered each year in the United States at nontraditional sites and by nontraditional vaccine providers. Pharmacists are increasingly becoming vaccine providers. OBJECTIVES: To measure association between availability of pharmacist-immunizers and immunization delivery to adult prescription recipients, and the relative contributions of various types of vaccine providers. RESEARCH DESIGN: Mailed survey in spring 1999, contrasting adults in urban Washington State, where pharmacists administer vaccines, to adults in urban Oregon, where pharmacists did not. SUBJECTS: Cluster sample based on October 1998 prescription records suggesting need for influenza vaccine, derived from 24 community pharmacies belonging to one pharmacy chain. MEASURES: Vaccination status and choice of vaccine provider. RESULTS: Influenza vaccination rates among respondents 65 years or older increased 4.7% more in Washington than in Oregon between 1997 and 1998 (P = 0.20). The net increase in influenza vaccination rate among younger respondents taking indicator medications for chronic diseases for which influenza vaccination is recommended was 10.6% (P = 0.05). Among respondents unvaccinated against influenza in 1997, the 1998 influenza vaccination rate was 34.7% in Washington, compared with 23.9% in Oregon (P = 0.01). CONCLUSIONS: Vaccine delivery by pharmacists is associated with higher rates of vaccination among those younger than 65 taking indicator medications medications for chronic diseases, as well as prescription recipients unvaccinated against influenza in the previous year.

Adult↗
PubMed2001

The influence of a family program on adolescent tobacco and alcohol use.

OBJECTIVES: This study examined a family-directed program's effectiveness in preventing adolescent tobacco and alcohol use in a general population. METHODS: Adolescents aged 12 to 14 years and their families were identified by random-digit dialing throughout the contiguous United States. After providing baseline data by telephone interviews, they were randomly allocated to receive or not receive a family-directed program featuring mailed booklets and telephone contacts by health educators. Follow-up telephone interviews were conducted 3 and 12 months after program completion. RESULTS: The findings suggested that smoking onset was reduced by 16.4% at 1 year, with a 25.0% reduction for non-Hispanic Whites but no statistically significant program effect for other races/ethnicities. There were no statistically significant program effects for smokeless tobacco or alcohol use onset. CONCLUSIONS: The family-directed program was associated with reduced smoking onset for non-Hispanic Whites, suggesting that it is worthy of further application, development, and evaluation.

Adolescent↗
PubMed2001

Biopharmaceutical statistics in a pharmaceutical regulated environment: past, present, and future.

The practice of statistics in the pharmaceutical industry has changed markedly over the last 25 years. This paper examines the evolution of clinical trial statistics in relationship to advances in statistical methodology and computational power as well as the changing regulatory environment. The current role of the biopharmaceutical statistician is assessed along with the drivers for future change.

Biopharmaceutics↗
PubMed2000

State scholarship, loan forgiveness, and related programs: the unheralded safety net.

CONTEXT: In the mid-1980s, states expanded their initiatives of scholarships, loan repayment programs, and similar incentives to recruit primary care practitioners into underserved areas. With no national coordination or mandate to publicize these efforts, little is known about these state programs and their recent growth. OBJECTIVES: To identify and describe state programs that provide financial support to physicians and midlevel practitioners in exchange for a period of service in underserved areas, and to begin to assess the magnitude of the contributions of these programs to the US health care safety net. DESIGN: Cross-sectional, descriptive study of data collected by telephone, mail questionnaires, and through other available documents, (eg, program brochures, Web sites). SETTING AND PARTICIPANTS: All state programs operating in 1996 that provided financial support in exchange for service in defined underserved areas to student, resident, and practicing physicians; nurse practitioners; physician assistants; and nurse midwives. We excluded local community initiatives and programs that received federal support, including that from the National Health Service Corps. MAIN OUTCOME MEASURES: Number and types of state support-for-service programs in 1996; trends in program types and numbers since 1990; distribution of programs across states; numbers of participating physicians and other practitioners in 1996; numbers in state programs relative to federal programs; and basic features of state programs. RESULTS: In 1996, there were 82 eligible programs operating in 41 states, including 29 loan repayment programs, 29 scholarship programs, 11 loan programs, 8 direct financial incentive programs, and 5 resident support programs. Programs more than doubled in number between 1990 (n = 39) and 1996 (n = 82). In 1996, an estimated 1306 physicians and 370 midlevel practitioners were serving obligations to these state programs, a number comparable with those in federal programs. Common features of state programs were a mission to influence the distribution of the health care workforce within their states' borders, an emphasis on primary care, and reliance on annual state appropriations and other public funding mechanisms. CONCLUSIONS: In 1996, states fielded an obligated primary care workforce comparable in size to the better-known federal programs. These state programs constitute a major portion of the US health care safety net, and their activities should be monitored, coordinated, and evaluated. State programs should not be omitted from listings of safety-net initiatives or overlooked in future plans to further improve health care access. JAMA. 2000;284:2084-2092.

Cross-Sectional Studies↗
PubMed2000

Non-parametric covariance methods for incidence density analyses of time-to-event data from a randomized clinical trial and their complementary roles to proportional hazards regression.

The principal response criteria for many clinical trials involve time-to-event variables. Usual methods of analysis for this type of response criterion include product-limit estimators of cumulative survival for the treatment groups, (stratified) logrank tests to compare treatments, and proportional hazards regression models with treatment and relevant covariates. When adjustment for covariates is of some importance, the relative roles of these methods may be of some concern, particularly for confirmatory clinical trials which must provide convincing findings to regulatory agencies. Unadjusted methods may have lower power, but there are issues regarding adjustment for covariates that may be controversial. These issues include applicability of proportional hazards assumptions, whether the correct model has been specified, and whether there is parallelism between treatments for relationships with covariates. One way to address these issues is to use non-parametric analysis of covariance strategies with extensions to log incidence density estimation. The principal basis for this method is no association between covariates and treatment groups as provided by randomized assignment of patients to groups. The background theory and strategies for computation are described for this method. Aspects of its application are illustrated for a clinical trial with two treatment groups and 722 patients. The objective of analysis for this clinical trial is evaluation of treatment effects with and without adjustment for 22 a priori covariates and a stratification for three geographical regions.

Disease Progression↗
PubMed2000

Prognostic value of exercise echocardiography in women in the community setting.

Treadmill stress echocardiography was performed in 1,136 women with known or suspected coronary artery disease whose clinical course was then evaluated a mean of 33 months later (range 12 to 60). The strongest predictor of an adverse outcome was the presence of a resting or an exercise-induced wall motion abnormality.

Adolescent↗
PubMed2000

Influence of a family-directed program on adolescent cigarette and alcohol cessation.

Programs to reduce adolescent cigarette or alcohol use by users in general populations have only recently been evaluated. Moreover, in spite of the substantial influence families have on their children, few family-directed programs designed to reduce the prevalence of adolescent smoking and drinking have been rigorously evaluated. This paper reports the findings of research designed to determine whether a family program reduced use of cigarettes or alcohol by users. The program consisted of a series of booklets mailed to families and follow-up telephone calls by health educators. A randomized experimental design involved families with children ages 12-14 throughout the United States. Data were collected by telephone at baseline and 3 and 12 months after the program was completed. No statistically significant program effects were observed for cessation or decrease in smoking and drinking by users.

Adolescent↗
PubMed2000

The Safe Dates program: 1-year follow-up results.

OBJECTIVES: An earlier report described desirable 1-month follow-up effects of the Safe Dates program on psychological, physical, and sexual dating violence. Mediators of the program-behavior relationship also were identified. The present report describes the 1-year follow-up effects of the Safe Dates program. METHODS: Fourteen schools were in the randomized experiment. Data were gathered by questionnaires in schools before program activities and 1 year after the program ended. RESULTS: The short-term behavioral effects had disappeared at 1 year, but effects on mediating variables such as dating violence norms, conflict management skills, and awareness of community services for dating violence were maintained. CONCLUSIONS: The findings are considered in the context of why program effects might have decayed and the possible role of boosters for effect maintenance.

Adolescent↗
PubMed1999

Multivariate non-parametric methods for Mann-Whitney statistics to analyse cross-over studies with two treatment sequences.

A non-parametric strategy for the analysis of ordinal data from cross-over studies with two treatment sequences and d(> or = 2) periods is examined through Mann-Whitney rank measures of association. For each period, these statistics estimate the probability of larger response for a randomly selected patient in one group relative to a randomly selected patient in the other group. Such estimates are as well formed for comparisons between groups for u pairs of periods with the same treatment. Methods for U-statistics are used to produce a consistent estimate of the covariance matrix for the (d + u) Mann-Whitney estimates. The effects of periods and treatments on the respective Mann-Whitney estimates are evaluated through linear (or log-linear) models. For estimation of the parameters in these models, a modified weighted least squares method is applied through a (2d - 1) < or = (d + u) dimensional basis which effectively addresses potentially near singularities in the estimated covariance matrix of the Mann-Whitney estimates. The proposed methods are applicable to response variables with an interval or an ordered categorical scale. Their scope additionally has capabilities for controlling strata in the design of a cross-over study or concomitant variables for which covariance adjustment is of interest for reduction of variance. Applications of the methods are illustrated through three cross-over studies with different specifications for the two sequences of two treatments during two to four periods.

Animals↗