| 1. |
- Bergenmar, M, et al.
(author)
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Levels of knowledge and perceived understanding among participants in cancer clinical trials - factors related to the informed consent procedure
- 2011
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In: Clinical trials (London, England). - : SAGE Publications. - 1740-7753 .- 1740-7745. ; 8:1, s. 77-84
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Journal article (peer-reviewed)abstract
- Background An informed consent from patients participating in cancer clinical trials is mandatory according to international and national guidelines and laws. Insufficient knowledge and understanding by trial participants have been reported in several studies. Purpose The aims of this study were to investigate factors of importance for knowledge and understanding about cancer clinical trials among trial participants. Methods All patients consenting to a phase II or III clinical trial during 1 year were invited ( n = 325). Data on knowledge and perceived understanding were collected by a questionnaire, Quality of Informed Consent. Results are based on data from 268 patients (82%). Associations between knowledge and perceived understanding as well as clinical, socio-economic factors, and factors related to the informed consent procedure were tested. Results In the multivariate analysis no statistically significant associations were found between knowledge and any of the factors. Patients who reported longer time for trial information before their decision to participate, those who found the decision easy to take, and patients who reported use of other information sources had statistically significant higher perceived understanding. No differences in mean scores for knowledge or perceived understanding were found for any of the clinical factors (age, gender, diagnostic group, trial phase), socio-economic factors (education, marital status), and the following factors related to the informed consent procedure; presence of relative or nurse at information about the trial or previous participation in clinical trials. Limitations No study specific questions were included due to the number of trials ( n = 35). Conclusion Strategies to increase patients’ knowledge needs to be elaborated in order to improve the fulfilment of the requirements of informed consent in participants in cancer clinical trials.
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| 2. |
- Franciscus, Margaret, et al.
(author)
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Recruitment and retention of participants for an international type 1 diabetes prevention trial : a coordinators' perspective.
- 2014
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In: Clinical Trials. - : SAGE Publications. - 1740-7745 .- 1740-7753. ; 11:2, s. 150-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Trial to Reduce Insulin Dependent Diabetes Mellitus in the Genetically at Risk (TRIGR) is the first multicenter international type 1 diabetes (T1D) prevention trial to be undertaken. A unique feature of TRIGR has been recruitment of eligible pregnant women and enrollment of newborns for long-term follow-up assessments.PURPOSE: Our purpose is to summarize the recruitment and retention strategies used to conduct TRIGR from the perspective of the study coordinators.METHODS: TRIGR was designed to test whether weaning to formula containing hydrolyzed versus intact cow's milk protein would be efficacious in decreasing risk for development of T1D-associated autoantibodies and T1D among infants identified to be at increased risk for T1D based on their human leukocyte antigen (HLA) profile and family history. Multiple strategies tailored to local issues were required to enroll and follow the target number of infants.RESULTS: This study was conducted in the United States, Canada, Australia, and 12 countries in Europe. Of the 5606 mothers registered worldwide, 5000 of their infants were randomized. Of these, 2159 were HLA eligible and enrolled in the 8-month intervention and 10-year follow-up phases of this study. The TRIGR study met the accrual goal after 4.7 years of recruitment, 2.7 years longer than projected initially. Challenges included difficulty in finding fathers with T1D, a higher than expected rate of premature delivery among T1D mothers, and implementation of new privacy regulations mid-trial. The majority of participants were recruited from primary care antenatal clinics located near the study centers and from a general hospital or pediatric center that was affiliated with a TRIGR Study center. Internet and magazine advertisements were found to be useful for recruitment of families. Alternative follow-up strategies are offered to families who wish to reduce or discontinue participation.LIMITATIONS: Our experience is limited to a single international multicenter trial.CONCLUSIONS: TRIGR coordinators played key roles in the recruitment and intervention periods and continue to be instrumental in retaining families and children during the 10-year follow-up period for each child.
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| 3. |
- Giobbie-Hurder, Anita, et al.
(author)
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Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.
- 2009
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In: Clinical trials (London, England). - : SAGE Publications. - 1740-7745 .- 1740-7753. ; 6:3, s. 272-87
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Journal article (peer-reviewed)abstract
- BACKGROUND: Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. PURPOSE: To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. METHODS: From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. RESULTS: The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. LIMITATIONS: Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. CONCLUSIONS: BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.
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| 4. |
- Hertzberg, Vicki, et al.
(author)
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Methods and processes for the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial
- 2008
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In: Clinical trials (London, England). - : SAGE Publications. - 1740-7745 .- 1740-7753. ; 5:4, s. 308-315
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Journal article (peer-reviewed)abstract
- With new NIH requirements for data-sharing, the frequency of re-analysis of clinical trial data may increase substantially. This re-evaluation provides a blueprint for future re-evaluations of other trials. These best practices include re-analysis of the study data, after suitable replication, by an independent multidisciplinary committee, including a skilled statistical programmer analyst. Primary investigators should address significant errors determined in such re-analyses.
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| 5. |
- Hilner, JE, et al.
(author)
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Designing and implementing sample and data collection for an international genetics study: the Type 1 Diabetes Genetics Consortium (T1DGC)
- 2010
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In: Clinical trials (London, England). - : SAGE Publications. - 1740-7753 .- 1740-7745. ; 7:1 Suppl, s. S5-S32
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Journal article (peer-reviewed)abstract
- Background and Purpose The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide. Methods T1DGC was organized into four regional networks (Asia-Pacific, Europe, North America, and the United Kingdom) and a Coordinating Center. A Steering Committee, with representatives from each network, the Coordinating Center, and the funding organizations, was responsible for T1DGC operations. The Coordinating Center, with regional network representatives, developed study documents and data systems. Each network established laboratories for: DNA extraction and cell line production; human leukocyte antigen genotyping; and autoantibody measurement. Samples were tracked from the point of collection, processed at network laboratories and stored for deposit at National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories. Phenotypic data were collected and entered into the study database maintained by the Coordinating Center. Results T1DGC achieved its original ASP recruitment goal. In response to research design changes, the T1DGC infrastructure also recruited trios, cases, and controls. Results of genetic analyses have identified many novel regions that affect susceptibility to type 1 diabetes. T1DGC created a resource of data and samples that is accessible to the research community. Limitations Participation in T1DGC was declined by some countries due to study requirements for the processing of samples at network laboratories and/or final deposition of samples in NIDDK Central Repositories. Re-contact of participants was not included in informed consent templates, preventing collection of additional samples for functional studies. Conclusions T1DGC implemented a distributed, regional network structure to reach ASP recruitment targets. The infrastructure proved robust and flexible enough to accommodate additional recruitment. T1DGC has established significant resources that provide a basis for future discovery in the study of type 1 diabetes genetics. Clinical Trials 2010; 7: S5—S32. http://ctj.sagepub.com
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| 6. |
- Karpefors, Martin, et al.
(author)
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The Maraca Plot : A Novel Visualization of Hierarchical Composite Endpoints.
- 2023
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In: Clinical trials (London, England). - : SAGE Publications. - 1740-7745 .- 1740-7753. ; 20:1, s. 84-88
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Journal article (peer-reviewed)abstract
- BACKGROUND: Hierarchical composite endpoints are complex endpoints combining outcomes of different types and different clinical importance into an ordinal outcome that prioritizes the clinically most important (e.g. most severe) event of a patient. Hierarchical composite endpoint can be analysed with the win odds, an adaptation of win ratio to include ties. One of the difficulties in interpreting hierarchical composite endpoint is the lack of proper tools for visualizing the treatment effect captured by hierarchical composite endpoint, given the complex nature of the endpoint which combines events of different types. METHODS: Hierarchical composite endpoints usually combine time-to-event outcomes and continuous outcomes into a composite; hence, it is important to capture not only the shift from more severe categories to less severe categories in the active group in comparison to the control group (as in any ordinal endpoint), but also changes occurring within each category. We introduce the novel maraca plot which combines violin plots (with nested box plots) to visualize the density of the distribution of the continuous outcome and Kaplan-Meier plots for time-to-event outcomes into a comprehensive visualization. CONCLUSION: The novel maraca plot is suggested for visualization of hierarchical composite endpoints consisting of several time-to-event outcomes and a continuous outcome. It has a very simple structure and therefore easily communicates both the overall treatment effect and the effect on individual components.
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| 7. |
- Mychaleckyj, Josyf C., et al.
(author)
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HLA genotyping in the international Type 1 Diabetes Genetics Consortium
- 2010
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In: Clinical Trials. - : SAGE Publications. - 1740-7753 .- 1740-7745. ; 7:1 suppl., s. 75-87
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Journal article (peer-reviewed)abstract
- Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loci in all affected sibling pair and trio families, and cases and controls, recruited from four networks worldwide, for analysis with clinical phenotypes and immunological markers. Purpose In this article, we present the operational strategy of training, classification, reporting, and quality control of HLA genotyping in four laboratories on three continents over nearly 5 years. Methods Methods to standardize HLA genotyping at eight loci included: central training and initial certification testing; the use of uniform reagents, protocols, instrumentation, and software versions; an automated data transfer; and the use of standardized nomenclature and allele databases. We implemented a rigorous and consistent quality control process, reinforced by repeated workshops, yearly meetings, and telephone conferences. Results A total of 15,246 samples have been HLA genotyped at eight loci to four-digit resolution; an additional 6797 samples have been HLA genotyped at two loci. The genotyping repeat rate decreased significantly over time, with an estimated unresolved Mendelian inconsistency rate of 0.21%. Annual quality control exercises tested 2192 genotypes (4384 alleles) and achieved 99.82% intra-laboratory and 99.68% inter-laboratory concordances. Limitations The chosen genotyping platform was unable to distinguish many allele combinations, which would require further multiple stepwise testing to resolve. For these combinations, a standard allele assignment was agreed upon, allowing further analysis if required. Conclusions High-resolution HLA genotyping can be performed in multiple laboratories using standard equipment, reagents, protocols, software, and communication to produce consistent and reproducible data with minimal systematic error. Many of the strategies used in this study are generally applicable to other large multi-center studies. Clinical Trials 2010; 7: S75-S87. http://ctj.sagepub.com.
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| 8. |
- Rylance, Rebecca T., et al.
(author)
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Assessing the external validity of the VALIDATE-SWEDEHEART trial
- 2021
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In: Clinical Trials. - : Sage Publications. - 1740-7745 .- 1740-7753. ; 18:4, s. 427-435
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Journal article (peer-reviewed)abstract
- Aims: The VALIDATE-SWEDEHEART trial was a registry-based randomized trial comparing bivalirudin and heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention. It showed no differences in mortality at 30 or 180 days. This study examines how well the trial population results may generalize to the population of all screened patients with fulfilled inclusion criteria in regard to mortality at 30 and 180 days.Methods: The standardized difference in the mean propensity score for trial inclusion between trial population and the screened not-enrolled with fulfilled inclusion criteria was calculated as a metric of similarity. Propensity scores were then used in an inverse-probability weighted Cox regression analysis using the trial population only to estimate the difference in mortality as it would have been had the trial included all screened patients with fulfilled inclusion criteria. Patients who were very likely to be included were weighted down and those who had a very low probability of being in the trial were weighted up.Results: The propensity score difference was 0.61. There were no significant differences in mortality between bivalirudin and heparin in the inverse-probability weighted analysis (hazard ratio 1.11, 95% confidence interval (0.73, 1.68)) at 30 days or 180 days (hazard ratio 0.98, 95% confidence interval (0.70, 1.36)).Conclusion: The propensity score difference demonstrated that the screened not-enrolled with fulfilled inclusion criteria and trial population were not similar. The inverse-probability weighted analysis showed no significant differences in mortality. From this, we conclude that the VALIDATE results may be generalized to the screened not-enrolled with fulfilled inclusion criteria.
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| 9. |
- Vickers, A. J., et al.
(author)
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Patient accrual and understanding of informed consent in a two-stage consent design
- 2021
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In: Clinical Trials. - : SAGE Publications. - 1740-7745 .- 1740-7753. ; 18:3, s. 377-382
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Journal article (peer-reviewed)abstract
- Background: We previously introduced the concept of "two-stage" (or "just-in-time") informed consent for randomized trials with usual care control. We argued that conducting consent in two stages-splitting information about research procedures from information about the experimental intervention-would reduce the decisional anxiety, confusion, and information overload commonly associated with informed consent. We implemented two-stage consent in a low-stakes randomized trial of a mindfulness meditation intervention for procedural distress in patients undergoing prostate biopsy. Here, we report accrual rates and patient understanding of the consent process. Methods: Patients approached for consent for the biopsy trial were asked to complete the standard "Quality of Informed Consent" questionnaire to assess their knowledge and understanding of the trial. Results: Accrual was excellent with 108 of 110 (98%) patients approached for consent signing first-stage consent. All 51 patients randomized to the experimental arm and who later presented for biopsy signed second-stage consent and received the mindfulness intervention. Quality of Informed Consent data were available for 48 patients assigned to the mindfulness treatment arm and 44 controls. The mean Quality of Informed Consent score was similar in the meditation and control arms with and overall mean of 75 (95% confidence interval = 74-76) for the knowledge section and 86 (95% confidence interval = 81-90) for understanding, comparable to the normative scores of 80 and 88. On further analysis and patient interview, two of the Quality of Informed Consent questions were found to be misleading in the context of a two-stage consent study for a mindfulness intervention. Excluding these questions increased knowledge scores to 88 (95% confidence interval = 87-90). Conclusion: We found promising data that two-stage consent facilitated accrual without compromising patient understanding of randomized trials or compliance with allocated treatment. Further research is needed incorporating randomized comparison of two-stage consent to standard consent approaches, measuring patient anxiety and distress as an outcome, using suitable modifications to the Quality of Informed Consent questionnaire and trials with higher stakes.
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| 10. |
- Vickers, A. J., et al.
(author)
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A randomized comparison of two-stage versus traditional one-stage consent for a low-stakes randomized trial
- 2023
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In: Clinical Trials. - 1740-7745. ; 20:6, s. 642-648
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Journal article (peer-reviewed)abstract
- Background/Aims It has been proposed that informed consent for randomized trials should be split into two stages, with the purported advantage of decreased information overload and patient anxiety. We compared patient understanding, anxiety and decisional quality between two-stage and traditional one-stage consent. Methods We approached patients at an academic cancer center for a low-stakes trial of a mind-body intervention for procedural distress during prostate biopsy. Patients were randomized to hear about the trial by either one- or two-stage consent (n = 66 vs n = 59). Patient-reported outcomes included Quality of Informed Consent (0-100); general and consent-specific anxiety and decisional conflict, burden, and regret. Results Quality of Informed Consent scores were non-significantly superior for two-stage consent, by 0.9 points (95% confidence interval = -2.3, 4.2, p = 0.6) for objective and 1.1 points (95% CI = -4.8, 7.0, p = 0.7) for subjective understanding. Differences between groups for anxiety and decisional outcomes were similarly small. In a post hoc analysis, consent-related anxiety was lower among two-stage control patients, likely because scores were measured close to the time of biopsy in the two-stage patients receiving the experimental intervention. Conclusion Two-stage consent maintains patient understanding of randomized trials, with some evidence of lowered patient anxiety. Further research is warranted on two-stage consent in higher-stakes settings.
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