Aspects Of Clinical Trials Research Articles

Decentralized clinical trials are better for the participants and for the planet: the case study of a double-blind randomized controlled trial in Singapore (PROMOTE study)

IntroductionNovel technologies have enabled the decentralization of many aspects of clinical trials, but little research has been done on the impact of these changes on the participant experience, trial operations, or the environment.MethodsA fully decentralized clinical trial conducted in Singapore is used as a case study to evaluate the operational outcomes, environmental impact (via life cycle assessment), and participants experience (qualitative interviews) of the decentralized model compared to a traditional study with in-person visits.ResultsThe decentralized study achieved high participant retention rates (97%) and high completion rates for clinical data, even for biological samples. Participants found the decentralized model to be convenient and safe, especially during the pandemic. Moreover, the decentralized model was found to be more environmentally friendly and less detrimental to human health compared to traditional face-to-face clinical trials, primarily by reducing participants’ use of cars for site visits.DiscussionWhile this study focused on the environmental impact, it is important to consider other factors such as participant safety, convenience, and data quality when evaluating the suitability of a decentralized clinical trial approach. Careful planning of data flow, database structure, and data protection measures is essential. This study contributes to improving the environmental footprint of clinical trials. Environmental sustainability should be among the factors that are evaluated when selecting trial models. Decentralized and hybrid clinical trials offer efficiency, effectiveness, and environmental benefits. Further research and adoption of these approaches are encouraged.

Investigator’s gender and clinical trials performance in recruitment of patients

Mostly of attraction to gender is related with participant subjects of clinical trials. Based on percentage of subject of each gender it is calculating enrollment fracture, bias and some other indexes. Enrollment is very important parameter and genders is considering as one of the internal factors which is influencing to enrollment. Authors also marking the more prevalence of male above the female in some aspects of clinical trials. It is obviously that investigators also has a differences in gender and this could have a differences in some parameters and enrollment is one of them. Enrolment parameters also not developed very much. We stepped forward to find out the relations of gender’s investigator and the enrollment. Materials and methods: Data of four clinical trials II-III phases in oncology and hematology, conducted since 2007 to 2017 years has been used for retrospective analysis. Study objectives: to investigate the study recruitment rate using different parameters and it’s changes along with acting of gender’s of investigator; to develop new parameters and values (derivatives) which could be sensitive for evaluation of enrollment. Statistical analysis: data had been collected from feasibility questionnaires, open statistical sources. Results: It was showed the values of enrollment parameters in perspective of investigator’s gender. Discussion: Statistical differences in some existing and developed enrollment parameters has been found. Gender’s influence to enrollment also was investigated.

Are We Scared of Clinical Trials if Not Sufficiently Informed and Educated?

Educational interventions have already been shown to positively affect awareness of clinical trials (CTs) among medical students. We aimed to explore basic knowledge and attitudes about CTs among medical students in terms of educational interventions that should be reflected in their further involvement in performing CTs and their role in raising awareness about CTs. This cross-sectional, self-report anonymous online survey involved undergraduate medical students of the Medical Faculty University of Sarajevo enrolled in classes held within the Department of Pharmacology and Toxicology in the academic year 2015-2016. To include all accessible subjects for better representation of the whole population, consecutive sampling was applied. Among 142 students who completed questionnaire, 50% of them expressed partial or full agreement with the questionnaire statement that they were satisfied with the available information on CTs. Only 38% said they would participate in a CT, 21% would not, while 41% were not sure. Positive correlations were detected for composite subscale scores of agreement with questionnaire statements conveying the student's knowledge about ethical and legal aspects of CTs and their perception about reliability/integrity and impact of CTs on medical practice. Students have knowledge of the basic design and ethical aspects of CTs. Positive attitudes toward the impact of CTs on medical practice were shown in students of higher years of study, where educational intervention of additional knowledge of CTs was inserted and those students expressed better knowledge of CTs. However, no significant impact was detected between knowledge and willingness to participate in CTs, irrespective of years of study, reflecting the third of students that would participate in CTs. Changes in medical curricula led to the change in students' knowledge and attitudes regarding CTs as well as their involvement in CTs.

Patient Recruitment System for Clinical Trials: Mixed Methods Study About Requirements at Ten University Hospitals.

BackgroundClinical trials are the gold standard for advancing medical knowledge and improving patient outcomes. For their success, an appropriately sized cohort is required. However, patient recruitment remains one of the most challenging aspects of clinical trials. Information technology (IT) support systems—for instance, patient recruitment systems—may help overcome existing challenges and improve recruitment rates, when customized to the user needs and environment.ObjectiveThe goal of our study is to describe the status quo of patient recruitment processes and to identify user requirements for the development of a patient recruitment system.MethodsWe conducted a web-based survey with 56 participants as well as semistructured interviews with 33 participants from 10 German university hospitals.ResultsWe here report the recruitment procedures and challenges of 10 university hospitals. The recruitment process was influenced by diverse factors such as the ward, use of software, and the study inclusion criteria. Overall, clinical staff seemed more involved in patient identification, while the research staff focused on screening tasks. Ad hoc and planned screenings were common. Identifying eligible patients was still associated with significant manual efforts. The recruitment staff used Microsoft Office suite because tailored software were not available. To implement such software, data from disparate sources will need to be made available. We discussed concrete technical challenges concerning patient recruitment systems, including requirements for features, data, infrastructure, and workflow integration, and we contributed to the support of developing a successful system.ConclusionsIdentifying eligible patients is still associated with significant manual efforts. To fully make use of the high potential of IT in patient recruitment, many technical and process challenges have to be solved first. We contribute and discuss concrete technical challenges for patient recruitment systems, including requirements for features, data, infrastructure, and workflow integration.

Optimization of adaptive designs with respect to a performance score.

Adaptive designs are an increasingly popular method for the adaptation of design aspects in clinical trials, such as the sample size. Scoring different adaptive designs helps to make an appropriate choice among the numerous existing adaptive design methods. Several scores have been proposed to evaluate adaptive designs. Moreover, it is possible to determine optimal two-stage adaptive designs with respect to a customized objective score by solving a constrained optimization problem. In this paper, we use the conditional performance score by Herrmann etal.(2020) as the optimization criterion to derive optimal adaptive two-stage designs. We investigate variations of the original performance score, for example, by assigning different weights to the score components and by incorporating prior assumptions on the effect size. We further investigate a setting where the optimization framework is extended by a global power constraint, and additional optimization of the critical value function next to the stage-two sample size is performed. Those evaluations with respect to the sample size curves and the resulting design's performance can contribute to facilitate the score's usage inpractice.

Regulatory aspects of clinical trials in case of emergency

The article deals with aprocedure of clinical trial of medical product for human use and describes regulatory aspects of а clinical trial in case of emergency, including the COVID-19 pandemic, analyses the grounds and conditions of studding properties of medical product, passed the state registration, for off-label use, without post-marketing clinical trial (low-interventional study). An assessment is made of the streamlined procedure of the registration of medical products, referring for the prophylactic and treatment of the diseases incase of emergency, andit is concluded about necessity ofextension this proceduretomedical products, which can be used for the treatment of other types of diseases.

Survey Results and Recommendations from Japanese Stakeholders for Good Clinical Practice Renovation

BackgroundThe International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is undertaking a major revision of ICH E6 Good Clinical Practice (GCP) decided to involve external stakeholders in ICH-GCP renovation. Activities such as surveys and public conferences have taken place in the United States, European Union, and Japan. For stakeholder engagement in Japan, a designated research group conducted a survey of academic stakeholders.MethodsA total of 105 academic stakeholders from 18 institutions responded to the survey. The research group developed recommendations reflecting the survey results and the opinions from patients and the public.ResultsThe survey showed the top four principles needing renovation were (i) informed consent (Chapter 2.9, 12.4% of respondents believed it needed renovation), (ii) systems for quality assurance (Chapter 2.13, 9.5%), (iii) information on an investigational product (Chapter 2.4, 5.7%), and (iv) procedures on clinical trial information (Chapter 2.10, 5.7%). The top three sections identified as needing renovation were: (i) informed consent (Chapter 4.8, 27.6%), (ii) monitoring (Chapter 5.18, 22.9%), and (iii) composition, functions, and operations of the ethics committee (Chapter 3.2, 14.3%). Recommendations included clarification of ICH-GCP’s scope, proportionality in various aspects of clinical trials, diversity and liquidity of ethics committee members, modernization of informed consent procedures, variations in monitoring, and regulatory grade when using real-world data.ConclusionThe recommendations from Japanese investigators and patients have been submitted to the ICH E6 Expert Working Group, which will strengthen the robustness of the GCP renovation.

Current ethical issues of clinical trials of drugs for the pathogenetic therapy of multiple sclerosis in the context of the COVID-19 pandemic

The spread of the COVID-19 pandemic posed a serious challenge for scientific and clinical medical institutions in terms of research for new multiple sclerosis (MS) treatments. In this review we discuss the associations between coronavirus infection and MS and provide data on the features of MS pathogenetic therapy during a pandemic. We also analyze the ethical aspects of clinical trials, the problems faced by researchers and patients, especially when using immunosuppressive therapy for MS. We provide examples of violations during research caused by the influence of a pandemic, as well as ways of solving them. Improving ethical standards is an essential component of ensuring the safety of MS and other immune-mediated diseases treatment.

Implementing oncology clinical trials in Nigeria: a model for capacity building

BackgroundThere is both higher mortality and morbidity from cancer in low and medium income countries (LMICs) compared with high income countries (HICs). Clinical trial activities and development of more effective and less toxic therapies have led to significant improvements in morbidity and mortality from cancer in HICs. Unfortunately, clinical trials remain low in LMICs due to poor infrastructure and paucity of experienced personnel to execute clinical trials. There is an urgent need to build local capacity for evidence-based treatment for cancer patients in LMICs.MethodsWe conducted a survey at facilities in four Teaching Hospitals in South West Nigeria using a checklist of information on various aspects of clinical trial activities. The gaps identified were addressed using resources sourced in partnership with investigators at HIC institutions.ResultsDeficits in infrastructure were in areas of patient care such as availability of oncology pharmacists, standard laboratories and diagnostic facilities, clinical equipment maintenance and regular calibrations, trained personnel for clinical trial activities, investigational products handling and disposals and lack of standard operating procedures for clinical activities. There were two GCP trained personnel, two study coordinators and one research pharmacist across the four sites. Interventions were instituted to address the observed deficits in all four sites which are now well positioned to undertake clinical trials in oncology. Training on all aspects of clinical trial was also provided.ConclusionsPartnerships with institutions in HICs can successfully identify, address, and improve deficits in infrastructure for clinical trial in LMICs. The HICs should lead in providing funds, mentorship, and training for LMIC institutions to improve and expand clinical trials in LMIC countries.

1253-P: Yields and Costs of Recruitment Methods with Participant Baseline Characteristics for a Diabetes Prevention Research Study in an Underserved Pediatric Population

Background: Diabetes disproportionately impacts Latino youth, yet few diabetes prevention programs (DPP) have prioritized inclusion of this vulnerable population. Recruitment is often the most challenging aspect of clinical trials and the optimal strategy to meet enrollment goals is unknown. This report describes the recruitment yields, costs, and baseline characteristics for a DPP focused on Latino youth. Methods: Recruitment methods included clinics, community efforts, media, and word-of-mouth with the goal of enrolling 120 Latino youth age 12-16 with obesity and prediabetes. Yields, costs, and baseline characteristics of youth were compared by recruitment method with final prediabetes eligibility determined by an Oral Glucose Tolerance Test (OGTT). Results: Recruitment spanned 47 months and yielded 655 referrals from clinics (N=344), community efforts (N=143), media (N=137), and word-of-mouth (N=31). From this pool, 50% (N=325) declined participation and 14% (N=93) were ineligible by general inclusion criteria. A screening OGTT was performed on 237 youth with 52% (N=122) meeting prediabetes eligibility and 117 subsequently randomized. The clinical sites yielded the highest number of total referrals (53%, N=344/655) while word-of-mouth yielded the highest proportion (35%, N=11/31) of randomized participants per referral. There were no significant differences in anthropologic or diabetes risk biomarkers between recruitment sources. Community recruitment efforts were the most costly ($486/randomized participant) followed by media ($236/randomized participant) and clinic ($248/randomized participant). Conclusions: These data suggest that yields and costs to recruit Latino youth into a DPP vary by method, and there were no differences in youth diabetes risk profiles. Recruiting hard-to-reach populations into clinical trials requires multiple strategies to meet target enrollment. Disclosure K.B. Vander Wyst: None. M. Olson: None. E.G. Soltero: None. Y.P. Konopken: None. C. Keller: None. F. González Castro: None. A. Williams: None. A.D.R. Fernandez: None. E. Hooker: None. D.L. Patrick: None. S. Ayers: None. H.H. Hu: None. A. Pena: None. W.C. Knowler: None. G.Q. Shaibi: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK10757901)

Need for better evidences and methodological aspects of clinical trials in snakebites

Need for better evidences and methodological aspects of clinical trials in snakebites

‘Real-world’ comparison of first-line direct aspiration and stent retriever mechanical thrombectomy for the treatment of acute ischemic stroke in the anterior circulation: a multicenter international retrospective study

BackgroundThrombectomy for anterior large vessel occlusion less than 24 hours since last known well is now standard of care. Certain aspects of clinical trials may limit generalizability to ’real-world' practice.ObjectiveTo...

Research Techniques Made Simple:Teledermatology in Clinical Trials

Telemedicine is well established as a means of providing high-quality healthcare at a distance, particularly to patients in underserved populations. Technologies in teledermatology can be used to complement traditional methodologies of clinical trials, expanding accessibility of trials to people typically unable to participate in research. Tools of communication technology may enhance many aspects of clinical trials in dermatology, from recruitment and retention of participants to collection of real-time data. Clinical trials can be made completely virtual or incorporate aspects of virtual technologies at any stage of research. Virtual clinical trials are considered highly patient-centered, as the ability of participants to engage with research staff from their own home often supplants the need for many or all on-site clinic visits. As technological advances influence every aspect of modern life, clinical trials will also evolve to incorporate these tools, meeting participant expectations and overcoming traditional challenges of conducting research. Virtual clinical trials come with specific issues pertaining to analysis of data, technology, and oversight. As more virtual trials are conducted, advantages and limitations of using such technology in research will become clearer and regulatory guidelines will be more firmly established.

Knowledge of medical students on clinical trials

Background: Basic research can help medical school students improve critical thinking skills required by medical practice. In this era of evidence-based medicine, the combination of medical education with clinical research is the key to ensure scientific discoveries are translated into clinical practice. This study’s objective was to know the awareness about clinical trials among undergraduate medical students.Methods: After obtaining approval from the Institutional Ethics Committee of NRI Academy of Medical Sciences, Guntur, India, this cross sectional study was conducted in second year medical students after taking their consent. A sample of 90was considered for statistical analysis. A structured questionnaire was used to measure the objective of this study, which had general, regulatory and ethical questions related to clinical trials. Qualitative data variables were expressed by using frequency and Percentage (%).Results: Out of 90 students, it was observed that in the general questions category, 70% of students were aware of the purpose of conducting clinical trials, 50% were aware of the pre-requisites for a participant before participating in a clinical trial and 50% were aware of the parameters evaluated in a clinical trial. 95% of students did not know the response for regulatory questions. The students’ awareness regarding ethics related to clinical trials was better than the other two categories.Conclusions: The overall awareness of clinical trials was low among students though they demonstrated good awareness regarding few aspects of clinical trials.

Herd immunity alters the conditions for performing dose schedule comparisons: an individual-based model of pneumococcal carriage

BackgroundThere is great interest in the use of reduced dosing schedules for pneumococcal conjugate vaccines, a strategy premised on maintaining an acceptable level of protection against disease and carriage of the organism. We asked about the practicality of measuring differential effectiveness against carriage in a population with and without widespread use of the vaccine for infants.MethodsWe adapted an existing transmission-dynamic, individual-based stochastic model fitted to the prevaccine epidemiology of pneumococcal carriage in the United States, and compared the observed vaccine-type carriage prevalence in different arms of a simulated trial with one, two, or three infant doses plus a 12-month booster. Using these simulations, we calculated vaccine efficacy that would be estimated at different times post-enrollment in the trial and calculated required sample sizes to see a difference in carriage prevalence.ResultsIn a pneumococcal conjugate vaccine (PCV)-naïve population, the difference in vaccine-type (VT) pneumococcal carriage prevalence between trial arms was less than 7% and varied with sampling time. In a population already receiving routine PCV administration, VT pneumococcal prevalence is nearly indistinguishable between trial arms. Relative efficacy of different dosing schedules was strongly dependent on the time between enrollment and sampling, with maximal prevalence differences reached 1–3 years post-enrollment. Moreover, vaccine efficacy estimates were typically slightly higher in trials in communities already receiving vaccination. Despite this, much larger sample sizes—by more than an order of magnitude—are required for a vaccine trial conducted in a population receiving routine PCV administration as compared to in a PCV-naïve population.ConclusionsThese findings highlight some underappreciated aspects of clinical trials of pneumococcal conjugate vaccines with efficacy endpoints, such as the context- and time-dependence of efficacy estimates. They support the wisdom of conducting comparative dose schedule trials of conjugate vaccine effects on carriage in vaccine-naïve populations.

Los aspectos bioéticos en los pacientes con cáncer tratados mediante ensayos clínicos en Cuba

Los aspectos bioéticos en los ensayos clínicos están regulados por organizaciones como la FDA, la Agencia Europea y, en Cuba, el Centro Nacional Coordinador de Ensayos Clínicos. El objetivo de este artículo es determinar la importancia de códigos, pautas y reglamentos para la seguridad y bienestar del sujeto de experimentación. Se ha utilizado como método la revisión sobre el tema de las bases de datos Medline, Hinari, Scielo, Springer, Wiley y otras en la página http://www.infomed.sld.cu. En conclusión, se analizaron los códigos, pautas y reglamentos sobre seguridad y bienestar del sujeto de experimentación, para que las personas con cáncer sean tratadas éticamente y no como medios u objetos.

A Questionnaire Survey on awareness of Clinical Trials Among Medical Students

There is an immense need to inculcate research in the medical curriculum of undergraduate medical students, which will help them to interpret the evidence based literature like journal articles, analyze, interpret & to help their decision making ability. Involvement in innovative research will help them develop a holistic attitude towards the patients especially in terms of informed consent and ethical decisions. This study a questionnaire survey was conducted on undergraduate medical students. It consists of statements spread over various aspects of clinical trials. The percentage of questions answered correctly in each group was graded as good, average and poor depending on scores. A total of 257 students participated in the study. Students had average knowledge about statements describing concept, need of clinical trial, participation, about Food and Drug Administration, informed consent had average knowledge. The response was poor for statements on Institutional Review Board (IRB) and Drug Controller General of India (DCGI). The medical undergraduates are future innovators, clinicians and scientific explorers. It would be better if they are trained at earlier days of learning about clinical trials/research and medical ethics these can be made a part of medical curriculum so that they can build their concrete future.

Implementation of imitation modelling for quantative risk assessment in clinical trial data collection

Appropriate data collection is an essential aspect of clinical trial (CT) quality and includes accurate and precise data entered into a case report form (CRF). The paper presents the results of risk assessment and modelling for the data collection process in the trial site. In research 292 CRF were analysed and CRF corrections documentation for 12 CT carried out in Clinical and Diagnostic Centre of the National University of Pharmacy (CDC NPhaU). In order to evaluate the rate of errors made in CRF we proposed a key risk indicator – error coefficient (k n ) with specific intervals of values: optimal (0-3); threatening (3,1-5); critical (more than 5). The model of the error coefficient changes was created by Monte-Carlo method and probability of critical values of the error coefficient was 0.026. The economic consequences for these cases were predicted by modelling on the basis of expert estimates regarding CT project time and required costs. Probability of the maximal project time increase to 4 days was 0.019; probability of maximal additional costs up to 3% of the budget was 0.02. The results obtained indicate the high quality of the data collection process in the CDC NPhaU. The method proposed may be recommended for sponsors for risk-based monitoring implementation, for trial sites preparing to monitoring visits, audits or inspections, for regulatory bodies for planning inspections of trial sites.

Probiotic and synbiotic safety in infants under two years of age

In this study, we systematically evaluated safety aspects in clinical trials with probiotics and synbiotics in young infants (0-2 years of age). This study is an update of earlier reports and covers the recent literature from 2008-2013. The safety evaluation is performed along the Common Terminology Clinical Adverse Events (CTCAE) version 4.0 scale, hereby also providing guidance for future studies. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. The results show a deficiency in the precise reporting and classification of adverse events in most studies. Analysis of 57 clinical trials with probiotics and synbiotics in combination with eight follow-up studies indicate that probiotic administration to infants between 0 and 24 months is safe with regard to the evaluated strains in infants with a particular health status or susceptibility. Most adverse events and serious adverse events were considered unrelated to the study product, and there were no major safety concerns. Almost all studies concluded that none of the adverse effects were related to the study product; the study products are generally well tolerated. Finally, inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes, greatly limit the generalizability of conclusions and argue convincingly for obligatory and standardised behaviour on adverse events (CTCAE) reporting in 'food' studies.

Lessons Learned from Negative Clinical Trials Evaluating Antithrombotic Therapy for Ischemic Heart Disease

The clinical trials that failed to demonstrate significant efficacy may not result in development of new therapy but contribute to better understanding of antithrombotic therapy for ischemic heart disease. Negative trials provide important messages about how to interpret and understand the results of clinical trials and apply these results to clinical practices. Although every aspect of clinical trials may influence the outcomes of trials and interpretation of their results, selection of study subjects, endpoints, and measuring risk/benefit are crucial to success of clinical trial. We will review the recent key negative trials on antithrombotic therapy for ischemic heart disease and discuss about their results and implications. The challenge in the future for the development of antithrombotic therapies is to leverage these "lessons learned" from negative clinical trials to improve the design, conduct, and interpretation of future randomized clinical trials.