Evaluation of the Informed Consent Process of a Multicenter Tuberculosis Treatment Trial.

BACKGROUND: Ethical principles obligate researchers to maximize study participants' comprehension during the informed consent process for clinical trials. A pilot evaluation of the consent process was conducted during an international clinical trial of treatment for pulmonary tuberculosis to assess the feasibility of conducting an evaluation in a larger population and to guide these future efforts. METHODS: Study staff administered an informed consent assessment tool (ICAT) to a convenience sample of trial participants, measuring comprehension of consent components as derived from the Common Rule and FDA Title 21 Part 50, and satisfaction with the process. Participating site staff completed a consent process questionnaire about consent practices at their respective sites and provided improvement recommendations. ICAT scores and corresponding practices were compared where both were completed. RESULTS: ICATs (n = 54) were submitted from one site in Spain (n = 10), one in Uganda (n = 30), and five in the United States (n = 14). Participants were primarily male (76%), born in Africa (n = 31, 57%), and had a median age of 27 years (interquartile range [IQR]: 24-42). Median ICAT scores were 80% (IQR: 67-93) for comprehension and 89% (IQR: 78-100) for satisfaction. Ugandan participants scored higher than participants from other sites on comprehension (87% vs. 64%) and satisfaction (100% vs. 78%). Staff from 14 sites completed consent process questionnaires. Median ICAT scores for comprehension and satisfaction were higher at sites that utilized visual aids. Practice recommendations included shorter forms, simpler documents, and supplementary materials. CONCLUSIONS: Participants achieved high levels (≥80%) of comprehension and satisfaction with their current consent processes. Higher ICAT scores at one site suggest an additional evaluation may identify approaches to improve comprehension and satisfaction in future trials. Through this pilot evaluation, complexities and challenges were identified in obtaining consent in a large, international multicenter trial and provided insights for a more robust assessment of the consent process in future trials.

Education level, primary language, and comprehension of the informed consent process.

TO OBTAIN INFORMATION ON HOW PERSONS from diverse backgrounds experience the informed consent process, we surveyed adults with a wide variety of educational levels and different primary languages (English, Spanish, or Vietnamese) who had recently enrolled in a study requiring written informed consent. Of the 100 participants, 62 were non-White, 43 had less than a high school education, and 60 had a primary language other than English. The median score for comprehension was 62% (IQR 50-76%); the median satisfaction score was 86% (IQR 71-100%). In multivariate analysis, only educational level was significantly associated with comprehension and satisfaction with the informed consent process (p < 0.001). Comprehension and satisfaction with the informed consent process were markedly lower among persons with lower educational levels.

Content Among Locally Approved HIPAA Authorization forms for Research.

THIS STUDY WAS DESIGNED TO ASSESS differences in the content of HIPAA authorization forms now required for clinical research. Authorization forms were collected from 111 institutions, including academic medical centers and commercial Institutional Review Boards. The requirement for an element covering the use of information acquired was fulfilled in 95% of the forms, and 100% had a statement fulfilling the core requirement of a description of the data to be collected. However, only 19% distinguished between entities that could see personal identifiers versus aggregate data. Significant differences existed in how long the disclosure agreement would remain in effect, and complex legalistic language was common. Thus, while research authorization forms technically met the requirements, the complex language and confusion over personal identifiers may raise concerns in prospective research participants.

Widespread emergence of methicillin resistance in community-acquired Staphylococcus aureus infections in Denver.

BACKGROUND: Increasing rates of methicillin resistance among out-patient Staphylococcus aureus infections led us to assess the epidemiology and outcome of a local outbreak. METHODS: A retrospective cohort study of outpatient skin and soft tissue infections due to S aureus in 2003. RESULTS: From 2002 to mid-2004, the percentage of outpatient S aureus isolates resistant to methicillin increased from 6 to 45%. In multivariate analysis, only male sex and age greater than 18 years were associated with methicillin resistance. Methicillin resistance was common (>15%) among isolates from patients in nearly all subgroups evaluated. Pulsed field gel electrophoresis showed isolates related to USA 300, but methicillin-resistant strains had unusually high rates of quinolone resistance. CONCLUSIONS: A single strain of methicillin-resistant S aureus is responsible for the increase in skin infections in outpatients without traditional risk factors for infection with an antibiotic-resistant strain. In areas with high rates of methicillin-resistant S aureus outpatient infections, we recommend non-beta-lactam antibiotics for initial treatment of skin and soft tissue infections.

The effectiveness of a verbal opt-out system for human immunodeficiency virus screening during pregnancy.

OBJECTIVE: We sought to evaluate the use of human immunodeficiency virus (HIV) screening during pregnancy in a health care system using the verbal opt-out method, in which HIV screening was recommended during all pregnancies and women were given an opportunity to refuse testing. METHODS: This was a retrospective cohort study of pregnancies resulting in delivery from 1998 through 2001 at Denver Health Medical Center, an urban public hospital. The main outcome measure was the proportion of documented HIV screening within 9 months before the delivery date. RESULTS: Of 12,221 pregnancies resulting in delivery, HIV screening was completed in 12,000 (98.2%, 95% confidence interval 97.9-98.4%). Of the 221 women not screened for HIV, only 24 (10.9% of those not screened, 0.2% of all women in the study) were documented as refusing HIV testing. Patients not screened for HIV presented late in pregnancy, a median of 1 day before delivery, compared with a median of 176 days for those who were screened (P <.001). CONCLUSION: A verbal opt-out system was very effective in promoting HIV screening during pregnancy. Late presentation in pregnancy was associated with not having HIV screening performed.

Conventional and molecular epidemiology of trimethoprim-sulfamethoxazole resistance among urinary Escherichia coli isolates.

BACKGROUND: Antibiotic resistance is increasing in Escherichia coli, the most common cause of urinary tract infections, but its epidemiology has not been well described. We evaluated the epidemiology of trimethoprim-sulfamethoxazole-resistant E. coli in a large, public health care system in Denver, Colorado. METHODS: Outpatients with E. coli urinary tract infections during the first 6 months of 1998 were evaluated retrospectively. A prospective study was then performed to confirm the rate of trimethoprim-sulfamethoxazole resistance. We used several strain-typing methods (pulsed-field gel electrophoresis, ribotyping, serotyping) to evaluate the molecular epidemiology of the resistance. RESULTS: The rate of trimethoprim-sulfamethoxazole resistance was similar in the retrospective (24% [161/681]) and prospective (23% [30/130]) phases of the study (P = 0.89). Almost all trimethoprim-sulfamethoxazole-resistant strains (98%) were resistant to at least one other antibiotic. Risk factors for infection with a resistant strain included age < or =3 years, Hispanic ethnicity, recent travel outside the United States, and a prior urinary tract infection. However, rates of resistance were >15% among nearly all of the subgroups. Most strains had high-level resistance (>1000 microg/mL) to trimethoprim-sulfamethoxazole. Of the 23 resistant isolates evaluated, 10 (43%) belonged to the clone A group. There was no correlation between conventional epidemiologic characteristics and the molecular mechanism of resistance or strain type. CONCLUSION: Resistance to trimethoprim-sulfamethoxazole among E. coli isolates among patients in a Denver public health care system is common, with high rates of resistance even among patients without risk factors.

The effects of local review on informed consent documents from a multicenter clinical trials consortium.

There is increasing controversy about the appropriate role of the local institutional review board in the review of multicenter clinical studies. We evaluated the effects of the local review process at 25 study sites on the consent forms from two studies of the Tuberculosis Trials Consortium, a multicenter trials group. Two independent reviewers classified all changes made in the centrally approved consent forms; a third reviewer evaluated those changes if the two initial reviewers disagreed. The median time to initial local approval was 104.5 days (range 31-346). There were no changes in the study protocols as a result of local review. Consent forms became longer and less readable after local review, with a mean increase in grade level of 0.9 (+/-0.9) reading grade levels (p<0.001). A median of 46.5 changes (range 3-160) were made in the centrally approved forms. Most changes (85.2%) involved altering wording without affecting meaning. Errors were commonly introduced (11.2% of changes), and 33 of 50 (66%) locally approved consent forms contained at least one error in protocol presentation or a required consent form element. Local approval of two multicenter clinical trials was time-consuming and resulted in many changes in centrally approved consent forms. These changes frequently decreased readability and introduced errors.