Biomedical subjects
Gary G Koch
Publications and source records attributed to Gary G Koch.
An index of patient reported outcomes (PRO-Index) discriminates effectively between active and control treatment in 4 clinical trials of adalimumab in rheumatoid arthritis.
OBJECTIVE: To analyze 2 indices composed of the 3 patient reported outcomes (PRO) in the American College of Rheumatology (ACR) Core Data Set--physical function, pain, and global estimate--without joint count or laboratory data, for capacities to distinguish active from control treatments in 4 pivotal clinical trials. METHODS: Data from 4 clinical trials involving adalimumab, in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARD) or as monotherapy, versus control treatment were made available to analyze properties of various indices. A categorical PRO-Index M was defined as "majority" improvement in 2 of the 3 PRO measures at 20%, 50%, and 70% levels; results were evaluated to analyze agreement with ACR20, ACR50, ACR70 responses and an "all Core Data Set measures" index based on 4 of the 7 measures having such levels of improvement. A continuous PRO-Index C was defined as the median or 2nd highest of 3 percentage differences from baseline to endpoint; results were evaluated to analyze agreement with a continuous ACR-N, "all Core Data Set measures" index, and Disease Activity Score 28 (DAS28). RESULTS: All indices distinguished active versus control treatment at similar levels, including PRO-Index M versus ACR20, ACR50, and ACR70 responses, and PRO-Index C versus DAS28. CONCLUSION: PRO indices based only on patient questionnaire data, without joint counts or laboratory tests, may be useful quantitative measures of therapeutic efficacy for use in standard rheumatology clinical care.
Community influenza activity and risk of acute influenza-like illness episodes among healthy unvaccinated pregnant and postpartum women.
This study investigated the relation between weekly levels of influenza activity and the risk of acute influenza-like illness episodes among 8,323 healthy pregnant and postpartum women enrolled in a Puget Sound region, Washington, health maintenance organization, Group Health Cooperative, between June 1991 and December 1997. The authors classified weeks between October and May for isolate activity level based on surveillance data for influenza, respiratory syncytial virus, parainfluenza, and adenovirus infection. Influenza-like illness episodes were identified from medical encounters assigned a diagnostic code consistent with a symptomatic influenza infection. The authors compared the occurrence of influenza-like illness episodes within each pregnancy stage for periods with varying levels of influenza isolate detection in the community. Repeated-measures logistic regression methods accounted for time-dependent factors. The adjusted strength of association between influenza exposure and influenza-like illness episodes increased as the pregnancy stage progressed (first trimester odds ratio = 1.12, 95% confidence interval: 0.79, 1.59; second trimester odds ratio = 1.30, 95% confidence interval: 0.97, 1.73; third trimester odds ratio = 1.84, 95% confidence interval: 1.31, 2.59; postpartum period odds ratio = 2.28, 95% confidence interval: 1.42, 3.68). Pregnancy stage modified the association between influenza activity and influenza-like illness episodes. Findings estimate that 20-43 pregnant/postpartum women would need to be vaccinated with an 80% effective vaccine to prevent one influenza-like illness episode.
Continuous indices of core data set measures in rheumatoid arthritis clinical trials: lower responses to placebo than seen with categorical responses with the American College of Rheumatology 20% criteria.
OBJECTIVE: To describe indices that are continuous counterparts of categorical responses to the American College of Rheumatology 20% improvement criteria (ACR20), ACR50, and ACR70, which extend rheumatoid arthritis (RA) clinical trial results and recognize clinical worsening (as well as improvement) with active and placebo treatments. METHODS: Data from a clinical trial of leflunomide, methotrexate, and placebo treatment over 1 year were reanalyzed. Percent change was computed for each of the 7 components of the ACR core set of outcome measures. Four continuous indices were computed: 1) ACR-N (lowest of 3 values: number of swollen joints, number of tender joints, and median of the other 5 measures); 2) composite (median of all 7 measures [3 patient and 3 assessor measures plus erythrocyte sedimentation rate]); 3) patient-only (median of physical function, pain, and global status); and 4) assessor-only (median of number of swollen joints, number of tender joints, and global status). Means, medians, categorical 20%, 50%, and 70% responses, and continuous probability plots were computed according to each index for the 3 treatment groups and were compared with one another and with standard ACR20, ACR50, and ACR70 responses. RESULTS: Mean levels of improvement calculated using the different methods, in patients taking leflunomide, placebo, and methotrexate, respectively, were as follows: ACR-N 20%, -12%, and 13%; composite 43%, 9%, and 33%; patient-only 36%, 0%, and 26%; assessor-only 50%, 20%, and 44%; and ACR20 52%, 26%, and 46%. Differences between leflunomide and placebo were 30-36%, and differences between methotrexate and placebo were 24-26%. CONCLUSION: Continuous indices may be an informative addition to categorical ACR 20%, 50%, or 70% responses to compare efficacies of various treatments in RA, and to describe lower responses to placebo by recognizing worsening as well as improvement.
Review and evaluation of methods for computing confidence intervals for the ratio of two proportions and considerations for non-inferiority clinical trials.
This article reviews several methods for forming confidence intervals for a risk ratio of two independent binomial proportions (which are both less than 0.50) and evaluates their statistical performance. These methods include use of a Taylor Series expansion to estimate variance, solutions to a quadratic equation, and maximum likelihood methods. In addition, for improvement of the properties of the methods based on large sample approximations, situations where either binomial count was less than or equal to 3 were managed conservatively by having an exact confidence interval for the odds ratio become the confidence interval for its risk ratio counterpart. Methods were initially evaluated by computing confidence limits for certain cases. Second, simulations were used to identify the better methods for controlling the Type I error rate while maintaining power. Last, relationships between methods were evaluated by calculating the percent of disagreement in the decision made regarding non inferiority. Methods in the group using a Taylor Series expansion in variance estimation perform similarly to the Pearson method preferred in the literature. In addition, the group of methods using a Taylor Series expansion are most easily computed. Applications of these findings are discussed for ratios that arise in randomized clinical trials that are conducted to show noninferiority of a new medical product to a reference control. Consideration is given as well to sample size calculations for noninferiority clinical trials.
Randomization-based nonparametric methods for the analysis of multicentre trials.
Multicentre trials offer several advantages over single centre trials in clinical research, including the ability to recruit patients at a faster rate over the course of the study, increased generalizability through the use of a broader patient population, and the ability to shed light on the replication of findings at multiple centres in a single study. A nonparametric approach to the analysis of multicentre trial data provides a convenient way for addressing the role of centres as well as baseline covariables during data analysis. With the use of randomization-based nonparametric methods, the strategy for evaluating the null hypothesis of no treatment effect can be prespecified during study planning without requiring a specific structure for the relationship of response criteria (or endpoints) to centres, covariables, or potential interaction terms. Further, the basis of inference for the application of these methods is the randomization mechanism, and the population to which inference can be directly made is the study population itself. No assumptions about underlying distributions, data structures, likelihood functions, or samples from super populations of inference are required. A three-step approach is proposed for handling centres via randomization-based nonparametric methods. In Step 1, a test of overall treatment effect is carried out using data from all centres simultaneously, without any assumption about treatment by centre interaction. In Step 2, the question of treatment by centre interaction is addressed, usually through the use of parametric multiple regression methods. In cases with suggestion of such interaction, Step 3 is conducted to evaluate different weighting schemes in forming pairwise treatment comparisons averaged across centres to assess the robustness of treatment effects observed in Step 1. An attractive inferential feature of this three-step approach is that the Type I error for the test of treatment effect is controlled by requiring statistical significance at each step to proceed to the next step. Extended Mantel-Haenszel methods with stratification adjustment for centre can be used to provide a nonparametric assessment of treatment effect. When adjustment for other covariates, such as baseline values, is desired, the more recent nonparametric analysis of covariance methods are available. Both methods are easy to use, require no assumptions beyond that of a valid randomization mechanism, and can be applied in a similar manner to dichotomous, ordinal, failure time, or continuous response criteria (endpoints). The methods are illustrated using data from a confirmatory clinical trial of a therapeutic agent for the treatment of dry eye disease.
Antidiabetic drugs and heart failure risk in patients with type 2 diabetes in the U.K. primary care setting.
OBJECTIVE: To assess the effects of antidiabetic drugs on the risk of heart failure in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study with a newly diagnosed diabetes cohort of 25,690 patients registered in the U.K. General Practice Research Database, 1988-1999. We categorized person-time drug exposures to monotherapies in insulin, sulfonylureas (SUs), metformins, and other oral hypoglycemic agents (i.e., acarbose, guar gum) and combination therapy including insulin, combination therapy without insulin, and triple combination therapy with or without insulin. A drug-free time interval served as a reference category. Cox interval-wise (piece-wise) regression analyses were used. The main outcome was incident heart failure. RESULTS: Among 43,390 drug exposure intervals for 25,690 patients who had a mean follow-up period of 2.5 years, 1,409 patients developed heart failure. Heart failure occurred most frequently in SU monotherapy exposure. After adjusting for duration of diabetes, the timing and order of treatments received, and known risk factors for heart failure, we found no differential effects among type-specific therapies. Patients with any drug use within the first year after diabetes diagnosis had a 4.75-fold higher risk (hazard ratio) for heart failure than those with drug-free status but had no increased risk during subsequent years. CONCLUSIONS: In conclusion, the use of any pharmacological therapy for type 2 diabetes appears to be associated with an increased risk of heart failure. This risk does not persist beyond the first year after diagnosis of diabetes and does not appear to differ among the types of drug therapy examined. This observation suggests that the severity of diabetes or the preclinical duration of diabetes and the need for drug therapy, and not the therapy itself, is an explanation for heart failure in patients with type 2 diabetes.
Patient preference in a crossover clinical trial of patients with osteoarthritis of the knee or hip: face validity of self-report questionnaire ratings.
OBJECTIVE: To analyze correlational validity of self-report responses regarding patient preference between 2 drugs at the conclusion of a crossover double-blind clinical trial in patients with osteoarthritis (OA) of the knee or hip. METHODS: Patients were randomized to 6 weeks' treatment of diclofenac/misoprostol or acetaminophen, followed by crossover to 6 weeks of the other drug. Patient preference was queried at the final visit: "Please compare control of your arthritis during the first and second periods as 'much better' or 'better' in the first period, 'no different' or 'better' or 'much better' in the second period." Patient preference ratings were evaluated in comparisons with 4 independent self-report measures within each treatment period: (1) change in Western Ontario McMaster (WOMAC) questionnaire scores; (2) change in pain visual analog scale (VAS) on a multidimensional Health Assessment Questionnaire (MDHAQ); (3) patient ratings of drug efficacy; and (4) patient report of change in arthritis status, as well as investigator ratings of the more efficacious drug. RESULTS: Among 173 patients, diclofenac/misoprostol was rated as "much better" by 54 and "better" by 45, acetaminophen was rated as "better" by 18 and "much better" by 17, and "no difference" by 39 patients. Spearman rank correlations for patient preferences were significant for changes in WOMAC scores, pain VAS, and independent patient ratings of drug efficacy and changes in arthritis status within each treatment period, as well as with physician ratings of the more efficacious drug (p < 0.001). CONCLUSION: Significant correlational validity is documented for patient self-report of preferences between 2 drugs compared to independent measures within each treatment period in this crossover clinical trial in patients with OA of the knee or hip.
A non-parametric procedure for evaluating treatment effect in the meta-analysis of survival data.
This paper addresses the problem of combining information from independent clinical trials which compare survival distributions of two treatment groups. Current meta-analytic methods which take censoring into account are often not feasible for meta-analyses which synthesize summarized results in published (or unpublished) references, as these methods require information usually not reported. The paper presents methodology which uses the log(-log) survival function difference, (i.e. log(-logS2(t))-log(-logS1(t)), as the contrast index to represent the multiplicative treatment effect on survival in independent trials. This article shows by the second mean value theorem for integrals that this contrast index, denoted as theta, is interpretable as a weighted average on a natural logarithmic scale of hazard ratios within the interval [0,t] in a trial. When the within-trial proportional hazards assumption is true, theta is the logarithm of the proportionality constant for the common hazard ratio for the interval considered within the trial. In this situation, an important advantage of using theta as a contrast index in the proposed methodology is that the estimation of theta is not affected by length of follow-up time. Other commonly used indices such as the odds ratio, risk ratio and risk differences do not have this invariance property under the proportional hazard model, since their estimation may be affected by length of follow-up time as a technical artefact. Thus, the proposed methodology obviates problems which often occur in survival meta-analysis because trials do not report survival at the same length of follow-up time. Even when the within-trial proportional hazards assumption is not realistic, the proposed methodology has the capability of testing a global null hypothesis of no multiplicative treatment effect on the survival distributions of two groups for all studies. A discussion of weighting schemes for meta-analysis is provided, in particular, a weighting scheme based on effective sample sizes is suggested for the meta-analysis of time-to-event data which involves censoring. A medical example illustrating the methodology is given. A simulation investigation suggested that the methodology performs well in the presence of moderate censoring.
Measures of morbidity in clinical studies with recurrent skeletal complications.
Double-blind placebo-controlled clinical trials in metastatic bone disease considered counts of morbid events as the clinical outcome measure. These (recurrent) skeletal events were derived from a composite endpoint based on the necessity of medical interventions against bone pain or incident fractures. The trials were conducted for regulatory approval of therapy with bisphosphonates and were intended to demonstrate that an active treatment reduces the occurrence of skeletal events. The advanced morbidity of the patients led to a substantial amount of premature discontinuations, because of early death or because of progression of the basic disease. In some trials the discontinuations were unbalanced between treatment arms, where there were more dropouts under placebo. These effects contribute to a high portion of patients with no morbidity events. This background presents difficulties for the task of defining statistics that validly quantify skeletal morbidity in these trials while keeping the necessary simplicity so as to be accepted by health authorities and a clinical audience. Guided by this regulatory context, this paper compares the performance of five (simple) approaches to quantifying skeletal morbidity. Key criteria are bias and validity under different dropout scenarios, as well as the capability to demonstrate treatment effects. Based on theoretical considerations, two simulation studies, and real data results, a morbidity measure in the form of a smoothed rate was favored: this is a rate estimate in the individual patient of the form (y + c)(T + d)(-1), where y is the count of events, T is the patient's observation time, and c, d are constants to be appropriately chosen. This morbidity measure performed well in the simulation studies and showed a wanted insensitivity to dropout patterns. It outperforms the simple rate y/T due to the high portion of patients without events. Rates of this type were used before in the quantal bioassay and have a strong relationship to Bayesian approaches. Hence, these measures represent a good approach to handle the inherent difficulties of morbid event data in severely diseased patient populations, still offering sufficient simplicity.
Type I error and power in noninferiority/equivalence trials with correlated multiple endpoints: an example from vaccine development trials.
Clinical trials necessary for the development of new treatment often require testing of multiple endpoints for equivalence or noninferiority relative to an existing effective standard therapy. An example is a vaccine study with multiple antibody measurements in sera of subjects receiving a combination vaccine such as a pneumococcal vaccine, which contains many different serotypes of the pneumococcal organism. This article describes testing methods for the demonstration of simultaneous marginal equivalence or noninferiority of two treatments on each component of the response vector that follows a multivariate normal distribution. Systematic simulation studies are conducted to evaluate the performance of the testing method and to examine under what conditions the power is substantially different if the multiple endpoints are assumed to be independent when they are actually strongly correlated. Data from an illustrative example are used to describe how the study power can be evaluated in the design of the trials.
Outcomes of states' scholarship, loan repayment, and related programs for physicians.
CONTEXT: Many states attempt to entice young generalist physicians into rural and medically underserved areas with financial support-for-service programs-scholarships, service-option loans, loan repayment, direct financial incentives, and resident support programs-with little documentation of their effectiveness. OBJECTIVE: The objective of this study was to assess outcomes of states' support-for-service programs as a group and to compare outcomes of the 5 program types. DESIGN: We conducted a cross-sectional, primarily descriptive study. PARTICIPANTS: We studied all 69 state programs operating in 1996 that provided financial support to medical students, residents, and practicing physicians in exchange for a period of service in underserved areas; federally funded initiatives were excluded. We also surveyed 434 generalist physicians who served in 29 of these state programs and a matched comparison group of 723 nonobligated young generalist physicians. DATA COLLECTION: Information on eligible programs was collected by telephone, mail questionnaires, and from secondary sources. Obligated and nonobligated physicians were surveyed, with 80.3% and 72.8% response rates, respectively. MAIN OUTCOME MEASURES: Levels of socioeconomic need of communities and patients served by physicians, programs' participant service completion and retention rates, and physicians' satisfaction levels. RESULTS: Compared with young nonobligated generalists, physicians serving obligations to state programs practiced in demonstrably needier areas and cared for more patients insured under Medicaid and uninsured (48.5% vs. 28.5%, P <0.001). Service completion rates were uniformly high for loan repayment, direct incentive, and resident-support programs (93% combined) but lower for student-targeting service-option loan (mean, 44.7%) and scholarship (mean, 66.5%) programs. State-obligated physicians were more satisfied than nonobligated physicians, and 9 of 10 indicated that they would enroll in their programs again. Obligated physicians also remained longer in their practices than nonobligated physicians (P = 0.03), with respective group retention rates of 71% versus 61% at 4 years and 55% versus 52% at 8 years. Retention rates were highest for loan repayment, direct incentive, and loan programs. CONCLUSIONS: States' support-for-service programs bring physicians to needy communities where a strong majority work happily and with at-risk patient populations; half stay over 8 years. Loan repayment and direct financial incentive programs demonstrate the broadest successes.
Effect of person-centered showering and the towel bath on bathing-associated aggression, agitation, and discomfort in nursing home residents with dementia: a randomized, controlled trial.
OBJECTIVES: To evaluate the efficacy of two nonpharmacological techniques in reducing agitation, aggression, and discomfort in nursing home residents with dementia. The techniques evaluated were person-centered showering and the towel bath (a person-centered, in-bed bag-bath with no-rinse soap). DESIGN: A randomized, controlled trial, with a usual-care control group and two experimental groups, with crossover. SETTING: Nine skilled nursing facilities in Oregon and six in North Carolina. PARTICIPANTS: Seventy-three residents with agitation during bathing (69 completed the trial) and 37 nursing assistants who bathed them. MEASUREMENTS: Agitation and aggression were measured using the Care Recipient Behavior Assessment; discomfort was measured using a modification of the Discomfort Scale for Dementia of the Alzheimer Type. Raters who were blinded to subject status coded both from videotaped baths. Secondary measures of effect included bath duration, bath completeness, skin condition, and skin microbial flora. RESULTS: All measures of agitation and aggression declined significantly in both treatment groups but not in the control group, with aggressive incidents declining 53% in the person-centered shower group (P<.001) and 60% in the towel-bath group (P<.001). Discomfort scores also declined significantly in both intervention groups (P<.001) but not in the control group. The two interventions did not differ in agitation/aggression reduction, but discomfort was less with the towel bath (P=.003). Average bath duration increased significantly (by a mean of 3.3 minutes) with person-centered showering but not with the towel bath. Neither intervention resulted in fewer body parts being bathed; both improved skin condition; and neither increased colonization with potentially pathogenic bacteria, corynebacteria, or Candida albicans. CONCLUSION: Person-centered showering and the towel bath constitute safe, effective methods of reducing agitation, aggression, and discomfort during bathing of persons with dementia.
Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders.
BACKGROUND & AIMS: Studies of antidepressants and psychological treatments in functional bowel disorders (FBD) are methodologically limited. The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy (CBT) against education (EDU) and desipramine (DES) against placebo (PLA) in female patients with moderate to severe FBD (irritable bowel syndrome, functional abdominal pain, painful constipation, and unspecified FBD). We also evaluated the amenability of clinically meaningful subgroups to these treatments. METHODS: This randomized, comparator-controlled, multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD. Participants received psychological (CBT vs. EDU) or antidepressant (DES vs. PLA) treatment for 12 weeks. Clinical, physiologic, and psychosocial assessments were performed before and at the end of treatment. RESULTS: The intention-to-treat analysis showed CBT as significantly more effective than EDU (P = 0.0001; responder rate, 70% CBT vs. 37% EDU; number needed to treat [NNT ], 3.1). DES did not show significant benefit over PLA in the intention-to-treat analysis (P = 0.16; responder rate, 60% DES vs. 47% PLA; NNT, 8.1) but did show a statistically significant benefit in the per-protocol analysis (P = 0.01; responder rate, 73% DES vs. 49% PLA; NNT, 5.2), especially when participants with nondetectable blood levels of DES were excluded (P = 0.002). Improvement was best gauged by satisfaction with treatment. Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms, abuse history, no depression, and diarrhea-predominant symptoms; CBT was beneficial over EDU for all subgroups except for depression. CONCLUSIONS: For female patients with moderate to severe FBD, CBT is effective and DES may be effective when taken adequately. Certain clinical subgroups are more or less amenable to these treatments.
Statistical approaches to effectiveness measurement and outcome-driven re-randomizations in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) studies.
The design of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia and Alzheimer's disease studies pose several statistical challenges, including issues related to performing multiple comparisons, defining effectiveness outcomes, and collecting and analyzing data from a design with multiple outcome-driven re-randomizations. We discuss the CATIE strategy for addressing many hypotheses within the context of one clinical trial while controlling the overall type I error rate. We provide motivation for the use of two effectiveness outcomes: time to all-cause discontinuation and composite endpoints that combine outcomes from multiple domains, such as efficacy, safety, cost-effectiveness, and quality of life. Methods for statistical analysis of an outcome-driven re-randomization trial are compared and evaluated. We describe analysis within each phase, analysis based on the first randomization or treatment algorithms, and repeated measures modeling. Finally, strategies are described for designing an electronic data collection system for trials with repeated outcome-driven re-randomizations.
National estimates of mortality rates for radical pancreaticoduodenectomy in 25,000 patients.
BACKGROUND: Recent publications suggest an inverse relationship between mortality rates in the Whipple procedure for periampullary cancer and hospital volume/teaching status. METHODS: The Nationwide Inpatient Sample database from 1988 to 1995, containing 24926 patients undergoing pancreatectomy for periampullary cancer, was used. RESULTS: The mean number of procedures per hospital per year was 1.5, and the overall mortality was 14%. The volume of procedures per year increased from the rural to the urban nonteaching hospitals to the urban teaching hospitals (.6, 1.1, and 2.7, respectively), with a steady decrease in mortality among the three hospital types (18%, 15%, and 11%). A multiple logistic regression model with mortality odds ratios (ORs) showed that male sex (OR, 1.3), increasing age (OR, 1.6 to 6.7 in decades from 50 to > or=80 vs. <50 years), emergency admission (OR, 1.5), and hospital volume (less than one vs. one or more cases per year; OR, 1.5) were significantly predictive for increased in-hospital mortality. CONCLUSIONS: In-hospital mortality in the low-volume hospital setting is prohibitive, and review of each institution's mortality rates must occur before these procedures are performed in those institutions. In addition, patients over the age of 60 years, male patients, and those with an urgent admission are at a significant risk of in-hospital death, and consideration should be given toward transfer to an experienced institution.
Attitudinal factors among adult prescription recipients associated with choice of where to be vaccinated.
The objective of this article was to evaluate adult prescription recipients' choices among vaccine providers. The study setting was a cluster sample from 24 community pharmacies based on prescription records that suggested need for pneumococcal and influenza vaccines. Vaccination status, choice of vaccine provider, and opinions regarding vaccine providers were retrospectively surveyed by mail in spring 1999. Overall, 52% of survey recipients responded; 89% of respondents reported returning to the same type of vaccine provider in consecutive years. Two key factors affected choice of provider: convenience and provider experience. Convenience was a stronger factor for people younger than 65 taking chronic medications and those not vaccinated in the previous year. Most adult recipients of influenza vaccine returned to sites where they were vaccinated the previous year. Convenience was a major factor in vaccination decisions of adult prescription recipients.
Influence of a family program on adolescent smoking and drinking prevalence.
Reducing the prevalence of adolescent cigarette smoking and alcohol drinking are public health goals of the United States. Although families have strong influence on their children, few randomized studies have examined whether family-directed programs influence those behaviors in general universal populations. This paper reports findings from an evaluation of a family program that features the mailing of four booklets to adult family members with follow-up telephone calls by health educators. A national sample of adolescent-parent pairs and a randomized experimental design were used to evaluate the program. Baseline users and nonusers of those substances were considered simultaneously in analyses so that program influences on smoking and drinking prevalence could be examined. The findings suggest that the program significantly reduced the prevalence of smoking cigarettes and drinking alcohol among adolescents. These findings are discussed in the context of earlier reports of research on the family program and implications for public health.