Роль информированного согласия в принятии решения об участии в исследовании: данные многоцентрового исследования в России «Лицом к лицу»

Introduction. Currently, clinical trials (CT) remain the only technology, which provides proof of efficacy and safety of new drugs and their subsequent release to the market. Medical researcher and informed consent (IC) are the main (and often the only) source of information for the patient about the upcoming clinical trials, and thus have a direct impact on the perception of clinical trials, and on the patient’s decision about participation. However, the degree of influence of these factors on the clinical trials participants still remains unclear.Materials and methods. A multicenter cross-sectional study was conducted in different cities of the Russian Federation. Patients who had previous experience in CTs (or were enrolled in a CT at the time of this study) were asked to complete a questionnaire.Results. To assess the impact of researcher, all respondents were divided into 2 groups: patients that acquainted with IC in collaboration with the researcher, and the other group, which reviewed IC form independently. We evaluated the importance of the factors influencing the decision-making process on participation in clinical trials. According to our data, the most important factors were professional monitoring services (3,72 ± 1,00), regular condition monitoring (3,66 ± 0,98), and better medical care (3,62 ± 1,00). These factors were evaluated at significantly lower score by group of patients that acquainted with IC together with the researcher (3,55 ±0,94, vs 4,01 ± 0,90, p = 0,002; 3,52 ± 1,01 vs 3,87 ± 0,90, p = 0,040; 3,49 ± 0,94, vs 3,83 ± 1,06, p = 0,020 respectively). In assessing the factors that had negative impact on the interest in participating in a clinical trial, the most significant were risk of side effects (3,01 ± 1,27), study of new medication (2,68 ± 1,21), and the risk of getting into the placebo group (2,64 ± 1,34) (so-called “objective” risk factors). At the same time, risk of side effects and risk of getting into the placebo group were also assessed at significantly lower score by group of patients that acquainted with IC together with the researcher (2,87 ± 1,28, vs 3,33 ± 1,17, p = 0,024; 2,51 ±1,25, vs 3,03 ± 1,34, p = 0,022 respectively). Furthermore, it was found that in the case of the researcher’s assistance acquaintance time with IC reduced threefold. We also evaluated the effect of the complexity of IC text on the decision-making process on participation in clinical trials. The group of respondents, who rated the IC as easy, appeared to be more interested in the final results of the study.Conclusion. Thus, when assessing the impact of the researcher on the review process of informed consent with the decision to participate in clinical trials, we found that in the case of assistance of the researcher, the acquaintance time with IC is reduced three times. In addition, this group of patients during the conversation with the researcher shows better and more clear understanding of the nature and general methodology of clinical trials, resulting in an adequate assessment “objective” risk factors for participation in clinical trials. Thus, this group of patients is more informed, compared with an “independent” group. According to the study “Face to Face”, we can recommend mandatory participation of a researcher during review process of the IC.Введение. В настоящее время клинические исследования (КИ) остаются единственной технологией, обеспечивающей доказательство эффективности и безопасности новых лекарственных средств и последующего их выхода на рынок. Врач-исследователь и информированное согласие (ИС) являются основными (и часто единственными) источниками информации для пациента о предстоящем КИ и тем самым непосредственно влияют на восприятие КИ и на решение пациента об участии. Однако до сих пор остается неясной степень влияния данных факторов на участников КИ.Материал и методы. В исследовании приняли участие девять центров, расположенных в разных городах Российской Федерации. Основным методом исследования являлось анкетирование пациентов. В рамках исследования пациенту, имеющему опыт участия в КИ и удовлетворяющему критериям отбора, однократно было предложено самостоятельно заполнить вопросник.Результаты. Для оценки влияния врача-исследователя все респонденты были поделены на две группы: пациенты, знакомившиеся с ИС совместно с врачом и самостоятельно. Самыми важными факторами, влияющими на принятие решения об участии в КИ, оказались: наблюдение профессиональными специалистами (3,72 ± 1,00), регулярное наблюдение за состоянием (3,66 ± 0,98) и более качественная медицинская помощь (3,62 ± 1,00). Данные факторы были оценены на достоверно более низкий балл группой пациентов, знакомившихся совместно с врачом (3,55 ± 0,94, vs 4,01 ± 0,90, p = 0,002; 3,52 ± 1,01, vs 3,87 ± 0,90, p = 0,040; 3,49 ± 0,94, vs 3,83 ± 1,06, p = 0,020 соответственно). При оценке факторов, отрицательно повлиявших на интерес к участию в клиническом исследовании, наиболее значимыми оказались: риск побочных явлений (3,01 ± 1,27), использование нового препарата (2,68 ± 1,21), а также риск попадания в группу плацебо (2,64 ± 1,34) (так называемые объективные факторы риска). При этом факторы – риск побочных явлений и риск попадания в группу плацебо – также были оценены на достоверно более низкий балл группой пациентов, знакомившихся с ИС совместно с врачом (2,87 ± 1,28, vs 3,33 ± 1,17, p = 0,024; 2,51 ± 1,25, vs 3,03 ± 1,34, p = 0,022 соответственно). Кроме того, установлено, что в случае помощи исследователя время ознакомления с ИС сокращается в три раза. Также отмечено влияние сложности текста ИС на принятие решения об участии в КИ. Группа респондентов, оценивших ИС как легкое, оказались более заинтересованы в конечных результатах исследования. Выводы. При оценке влияния исследователя на процесс ознакомления с информированным согласием принятия решения об участии в КИ установлено, что в случае помощи исследователя время ознакомления с информированным согласием сокращается в три раза. Кроме того, данная группа пациентов в ходе беседы с исследователем начинает ясно представлять суть и общую методологию клинических исследований, что выражается в адекватной оценке объективных факторов риска участия в клинических исследованиях. Таким образом, данная группа пациентов более информирована по сравнению с группой «самостоятельных» участников. По результатам исследования «Лицом к лицу» при проведении клинических исследований в дальнейшем рекомендуется обязательное участие врача при ознакомлении потенциальных участников с ИС

Role of Informed Consent in a Decision-making on Participation in The Clinical Trial: Multicenter study in Russia "Face to Face"

Introduction. Currently, clinical trials (CT) remain the only technology, which provides proof of efficacy and safety of new drugs and their subsequent release to the market. Medical researcher and informed consent (IC) are the main (and often the only) source of information for the patient about the upcoming clinical trials, and thus have a direct impact on the perception of clinical trials, and on the patient’s decision about participation. However, the degree of influence of these factors on the clinical trials participants still remains unclear.Materials and methods. A multicenter cross-sectional study was conducted in different cities of the Russian Federation. Patients who had previous experience in CTs (or were enrolled in a CT at the time of this study) were asked to complete a questionnaire.Results. To assess the impact of researcher, all respondents were divided into 2 groups: patients that acquainted with IC in collaboration with the researcher, and the other group, which reviewed IC form independently. We evaluated the importance of the factors influencing the decision-making process on participation in clinical trials. According to our data, the most important factors were professional monitoring services (3,72 ± 1,00), regular condition monitoring (3,66 ± 0,98), and better medical care (3,62 ± 1,00). These factors were evaluated at significantly lower score by group of patients that acquainted with IC together with the researcher (3,55 ±0,94, vs 4,01 ± 0,90, p = 0,002; 3,52 ± 1,01 vs 3,87 ± 0,90, p = 0,040; 3,49 ± 0,94, vs 3,83 ± 1,06, p = 0,020 respectively). In assessing the factors that had negative impact on the interest in participating in a clinical trial, the most significant were risk of side effects (3,01 ± 1,27), study of new medication (2,68 ± 1,21), and the risk of getting into the placebo group (2,64 ± 1,34) (so-called “objective” risk factors). At the same time, risk of side effects and risk of getting into the placebo group were also assessed at significantly lower score by group of patients that acquainted with IC together with the researcher (2,87 ± 1,28, vs 3,33 ± 1,17, p = 0,024; 2,51 ±1,25, vs 3,03 ± 1,34, p = 0,022 respectively). Furthermore, it was found that in the case of the researcher’s assistance acquaintance time with IC reduced threefold. We also evaluated the effect of the complexity of IC text on the decision-making process on participation in clinical trials. The group of respondents, who rated the IC as easy, appeared to be more interested in the final results of the study.Conclusion. Thus, when assessing the impact of the researcher on the review process of informed consent with the decision to participate in clinical trials, we found that in the case of assistance of the researcher, the acquaintance time with IC is reduced three times. In addition, this group of patients during the conversation with the researcher shows better and more clear understanding of the nature and general methodology of clinical trials, resulting in an adequate assessment “objective” risk factors for participation in clinical trials. Thus, this group of patients is more informed, compared with an “independent” group. According to the study “Face to Face”, we can recommend mandatory participation of a researcher during review process of the IC

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)