Generalizability Of Trial Results Research Articles

Overcoming the barriers to early-phase clinical trials (EPCT): Increasing EPCT minority accrual.

e16566 Background: Increasing minority accrual is critical to the development of novel cancer therapeutics. Without adequate minority representation in EPCT, researchers cannot assess differential effects among groups nor ensure the generalizability of trial results. Little is known about cultural factors that impact the decision to participate in EPCT among Hispanics. Methods: The goals of this research were to identify cultural, economic and environmental barriers to EPCT accrual and potential interventions to reduce these barriers. Two surveys were conducted. One survey was with 114 oncologists and one with 100 cancer patients (50 who were enrolled in an EPCT and 50 who never participated). Results: The top four logistical barriers stated by oncologists were all related to the extra work and time of recruiting and referring patients: referring patients is extra work (63%), too much paperwork (57%), too complex of procedures (57%) and excessive details of protocols (50%). Significant differences between clinical trial and non-clinical trial participants were found for two barriers in the decision-making process [lack of knowledge about available trials (88% and 94%), and lack of understanding about trial processes and purpose due to medical jargon (82% and 90%)]. Non-clinical trial participants gave higher importance to four barriers related to attitudes and beliefs [fear of being a guinea pig (80%), fear that the experiment is more important than the patient (76%), distrust in the medical system (72%), and fear of sacrificing QoL (72%)]. Non-participants in EPCT tended to have less education, lower income, and were Hispanic. In addition, two-thirds (68%) of non-participants considered language as a major barrier. Conclusions: Oncologists would be more likely to refer patients for EPCT if they are aware of the studies, feel confident with their patients, trust the research team, see benefit for their patients, and have an easy way to refer patients. The results of this study may have implications in terms of message development for groups traditionally underrepresented, which may require language appropriate materials, more visual materials with lower reading levels, and with more precise economic information.

Generalizing Evidence From Randomized Clinical Trials to Target Populations: The ACTG 320 Trial

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results.

Generalizability of Clinical Trial Results for Major Depression to Community Samples

Although emerging data indicate that sample composition may influence the effectiveness of mental health interventions, the extent to which subjects in clinical trials represent affected community samples remains unknown. The goal of this study was to assess the proportion of community-dwelling adults with major depressive episode (MDE) who would meet eligibility criteria for a traditional efficacy trial in patients with MDE. We applied a standard set of exclusion criteria used in clinical trials in patients with MDE to the 2001-2002 National Epidemiologic Survey for Alcohol and Related Conditions (NESARC), the largest psychiatric epidemiologic study in the United States to date (N = 43,093). Because individuals who seek treatment for a disorder may systematically differ from those who do not, we applied the criteria first to all individuals with a current diagnosis of MDE (N = 3119) (diagnosed according to DSM-IV) and then to the subsample of individuals who sought treatment (N = 1359). Among the full sample of individuals with MDE, 75.8% were excluded by one or more study eligibility criteria. Approximately two thirds (66.9%) of the subsample of those who sought treatment were excluded. The percentage of subjects excluded by individual study criteria ranged from 2.4% to 47.4% in the overall sample and 0% to 38.4% in the treatment-seeking sample. For both groups, the presence of comorbid, nondepressive, non-substance use Axis I disorders and the duration of the depressive episode excluded the largest percentage of individuals. The design of traditional clinical trials tends to exclude a majority of individuals with MDE. Selection of exclusion criteria may have a powerful influence on the generalizability of study results. Clinical trials should explain the rationale for their exclusion criteria and estimate the impact of eligibility criteria on the generalizability of trial results.

Characteristics of patients with irritable bowel syndrome recruited from three sources: implications for clinical trials.

Variation in the characteristics of irritable bowel syndrome patients recruited for clinical trials from different sources could affect their response and the generalizability of trial results. To describe and compare the characteristics of three different groups of irritable bowel syndrome patients recruited into a 'mock clinical trial.' We enrolled 245 irritable bowel syndrome patients from three sources: (i) 121 from British primary practitioners; (ii) 72 from California newspaper advertisements; and (iii) 52 from a California gastroenterologist's practice. We obtained demographic, clinical, and Hospital Anxiety and Depression (HAD) Scale data. Most patients were young to middle-aged women; the majority reported symptoms for > 5 years in all three groups. Subject characteristics varied among the groups. Typically, primary care patients were anxious, smokers and daily alcohol drinkers who had sought care recently for irritable bowel syndrome and tried antispasmodic drugs. Their symptoms were intermediate in severity between those of the other two groups. Advertisement subjects were the oldest, most highly educated, most often depressed, and were least likely to have sought care recently for symptoms, which were almost uniformly only moderate in severity. Gastroenterologist patients tended to be anxious and had nearly all sought care recently for symptoms, which were the most severe and most likely to include all three pain-related Rome I criteria. Recruitment methodology affects important characteristics of an irritable bowel syndrome study group.

Black participation in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial

The primary goal of the Prostate, Lung , Colorectal and Ovarian (PLCO) Cancer Screening Trial is to learn whether widespread use of screening tests to detect these cancers will reduce associated mortality. Blacks have the highest age-adjusted cancer incidence and mortality rates of any population group in the United States, but several barriers to their participation in clinical research such as the PLCO trial exist. These barriers involve sociocultural, economic, and individual factors, as well as factors inherent in trial designs. Population diversity in the PLCO trial is necessary to preserve scientific validity and generalizability of trial results. Therefore, the National Cancer Institute and the Centers for Disease Control and Prevention are collaborating to ensure adequate representation of blacks in the PLCO trial. For example, the agencies have funded several new activities designed to better understand and overcome barriers to participation in the trial. These activities include the African American Men Project, a randomized trial designed to evaluate the efficacy of three increasingly intensive recruitment interventions in recruting black men; the establishment of a minority-focused PLCO trial screening center, a study of identify factors that influence the decisions of black women recruited to participate in the PLCO trial; and a study to examine the psychosocial factors that influence blacks' decision making to engage in cancer screening and participation in research similar to the PLCO trial. The results of these activities will allow for a more thorough examination of cancer-related issues of importance to blacks and will help shed light on factors that influence their decisions to participate in cancer screening and prevention clinical trials.

Recruitment in AIDS Clinical Trials: Investigation of Sociodemographic and Psychosocial Factors Affecting Participation in Clinical Research

The primary objective of this study was to identify the social, psychological, and behavioral factors that influenced recruitment in AIDS clinical trials. The study compared HIV-infected individuals participating in a trial (n = 113) and a group of HIV-infected patients not currently participating in a trial (n = 103). Trial participants were more likely to be White (61.5% vs. 38.8%, p < .004), MSM (40.7% vs. 20.4%, p < .0001), with no IDU history (74.0% vs. 38.8%, p < .0001). Among trial nonparticipants, 42.2% indicated willingness to participate in a trial. Gender, race, and IDU history was not related to willingness to participate in a trial. Trial nonparticipants rated almost all aspects of the trial regimen as significantly more difficult compared to trial participants. Trial participants differed significantly on sociodemographic dimensions and in beliefs and attitudes toward medical therapies. These differences may limit the generalizability of trial results and, consequently, the effectiveness of HIV therapeutics.