Complexity Of Clinical Research Research Articles

Understanding the needs and perspectives of ovarian cancer patients when considering PARP inhibitor maintenance therapy: Findings from two online community events

ObjectiveThe online environment is an ideal setting to understand how many women seek, receive, and understand information about cancer treatment. The purpose of this study was to understand women’s needs and information-seeking around Poly ADP ribose polymerase (PARP) inhibitors, an oral medication commonly prescribed as maintenance therapy at the conclusion of primary chemotherapy for ovarian cancer. MethodsWe held online discussion events with two social media communities, #gyncsm social media on Twitter and the Smart Patients ovarian cancer community, in November 2020, to sample ovarian cancer patient perceptions of, and information seeking about PARP inhibitors. Focused questions were presented to both communities, with participants able to answer and elaborate upon these questions, as well as to add their own comments or topics. Qualitative content analysis was performed on the transcripts from the two online events. ResultsA total of 254 unique tweets and 71 messages were generated from the Twitter and Smart Patients conversations, respectively. The majority of the content from these two events could be categorized into five major themes: (1) concerns about side effects, (2) expectations of benefit, (3) desire for more information regarding clinical trials, ) (4) desire to better understand the relationship between mutation status and PARP inhibitor effectiveness, and (5) financial toxicity. Misinformation was rarely identified. ConclusionsWomen with ovarian cancer who are engaged in online patient communities have numerous educational needs regarding PARP inhibitors. Given the complexity of clinical research on PARP inhibitors, patients would likely benefit from patient-centered educational tools.

Are We Ready to Accept Follow-up Rates of 50% in Orthopaedic Research?: Commentary on an article by OME Cleveland Clinic Orthopaedics: "Value in Research: Achieving Validated Outcome Measurements While Mitigating Follow-up Cost".

Commentary Research is important, but bias is everywhere1. Bias is defined as systematic deviation from the truth. Bias is different from non-systematic deviation from the truth, which is simply noise1. We seek research free from bias to answer clinical questions. The results of research are used by surgeons to make clinical decisions and to thereby improve care. The problem with bias is that it can lead to flawed conclusions on study questions1. Flawed conclusions can lead to wrong decisions and poor care. Reduction of bias is integral to the design and analyses of all research. In terms of design, holding all other things constant, randomized studies are generally more valid than nonrandomized studies, prospective studies are generally more valid than retrospective studies, and controlled studies are generally more valid than uncontrolled studies. These generalizations are the basis of Levels of Evidence2. Higher levels of research are generally freer from bias and more valid. However, there are well-performed Level-II studies that are less biased than a poorly performed Level-I study. This is because there are upwards of 100 described sources of bias, many of which can affect the results of any study1. Of the many sources of bias, a particularly important issue is how, when, and what percentage of the study population is assessed for study outcomes. Gaining a sufficient number of eligible patients to consent to participate is the first challenge in meeting sample size requirements. The final challenge is ensuring that a sufficient number of patients are available to ascertain study outcomes. Given that almost no studies achieve 100% follow-up, this potentially introduces bias1. The importance of loss to follow-up is dependent on whether patients are missing at random or not missing at random3. If patients are missing at random, then their missing data are simply noise. However, if the loss to follow-up is not random, then the frequency and how much missing patients deviate from the true population can affect the study results. For example, if patients with worse outcomes seek care somewhere else and are lost to follow-up, this can falsely elevate the rates of positive outcomes. The acceptable rate of missing data has been arbitrarily set at 20%. More than 20% loss to follow-up is generally believed to be problematic, whereas <5% loss to follow-up is generally believed to pose a minimal risk of bias4. However, as stated above, the risk is dependent on the amount of deviation from the truth, so that any threshold short of 100% follow-up cannot guarantee unbiased results. In their study, Spindler et al. evaluate different methods of follow-up and the effect on patient-reported outcome measures (PROMs). The traditional methods of in-person follow-up are being replaced in many studies by automated follow-up such as text and/or emails. Automated methods are appropriate and useful when patients do not need to be seen in person and the outcome such as a PROM can be validly obtained by automated methods. Manual methods such as telephone calls or in-person visits are used to achieve a higher percentage of follow-up, but these methods are expensive. The study by Spindler et al. demonstrated that manual follow-up increased response rates by >20%. However, despite differences in baseline characteristics between those receiving manual follow-up and those receiving automated follow-up, there was no clinically meaningful or significant difference in PROM scores. Thus, if the study had used a solely automated technique, a loss to follow-up of approximately 50% would not have affected the study outcomes. This research could have important implications for reducing the cost and complexity of clinical research. Boosting follow-up rates to get closer to 80% follow-up might not be needed. However, this is only 1 study in 1 setting, and the generalizability of the results to other settings is uncertain. Thus, the study must be replicated in other settings, with other outcomes and other types of interventions. Although exciting, orthopaedics is not yet ready to accept follow-up rates of 50% based on a single study in a single setting.

Exploration of Vitamin D Supplementation Adjuvant Therapy for Childhood Asthma and the Best Treatment Options

Vitamin D not only promotes the health of human bones and muscles but also has an important impact on the metabolism of extraskeletal tissues. As a steroid hormone, vitamin D possesses important physiological functions, including cell differentiation and proliferation and immune regulation. Research has shown that vitamin D insufficiency (VDI) or vitamin D deficiency (VDD) can make children susceptible to asthma. Vitamin D has important immunoregulatory functions associated with preventing the occurrence of asthma or the worsening of its symptoms, improving lung function and enhancing glucocorticoid (GCS) action. An increasing number of randomized controlled intervention studies have confirmed that vitamin D affects the occurrence and development of asthmatic diseases. In recent years, accumulating laboratory and clinical research has supported the use of vitamin D as an adjuvant treatment for asthma and has achieved good clinical results. But the clinical outcome of vitamin D in the treatment of asthma is not as impressive as experimental studies. In addition to the complexity of clinical research, it may be related to clinical application methods. In order to combine theory with clinical practice, focused on exploring and selecting the most effective vitamin D adjuvant treatment of asthma, and comprehensively optimizing and applying these methods is beneficial to improve the therapeutic effect. However, there are different opinions regarding the results of the studies.

Patients with advanced non-small cell lung cancer (NSCLC): Are research biopsies a barrier to participation in clinical trials?

6534 Background: The evolution of targeted therapy in NSCLC has led to growing complexity of clinical research and a heightened expectation of clinical benefit for participants. Clinical trials in ...

A domain analysis model for eIRB systems: Addressing the weak link in clinical research informatics

Institutional Review Boards (IRBs) are a critical component of clinical research and can become a significant bottleneck due to the dramatic increase, in both volume and complexity of clinical research. Despite the interest in developing clinical research informatics (CRI) systems and supporting data standards to increase clinical research efficiency and interoperability, informatics research in the IRB domain has not attracted much attention in the scientific community. The lack of standardized and structured application forms across different IRBs causes inefficient and inconsistent proposal reviews and cumbersome workflows. These issues are even more prominent in multi-institutional clinical research that is rapidly becoming the norm. This paper proposes and evaluates a domain analysis model for electronic IRB (eIRB) systems, paving the way for streamlined clinical research workflow via integration with other CRI systems and improved IRB application throughput via computer-assisted decision support.

Oversight of human participants research: identifying problems to evaluate reform proposals.

The oversight of research involving human participants is widely believed to be inadequate. The U.S. Congress, national commissions, the Department of Health and Human Services, the Institute of Medicine, numerous professional societies, and others are proposing remedies based on the assumption that the main problems are researchers' conflict of interest, lack of institutional review board (IRB) resources, and the volume and complexity of clinical research. Developing appropriate reform proposals requires carefully delineating the problems of the current system to know what reforms are needed. To stimulate a more informed and meaningful debate, we delineate 15 current problems into 3 broad categories. First, structural problems encompass 8 specific problems related to the way the research oversight system is organized. Second, procedural problems constitute 5 specific problems related to the operations of IRB review. Finally, performance assessment problems include 2 problems related to absence of systematic assessment of the outcomes of the oversight system. We critically assess proposed reforms, such as accreditation and central IRBs, according to how well they address these 15 problems. None of the reforms addresses all 15 problems. Indeed, most focus on the procedural problems, failing to address either the structure or the performance assessment problems. Finally, on the basis of the delineation of problems, we outline components of a more effective reform proposal, including bringing all research under federal oversight, a permanent advisory committee to address recurrent ethical issues in clinical research, mandatory single-time review for multicenter research protocols, additional financial support for IRB functions, and a standardized system for collecting and disseminating data on both adverse events and the performance assessment of IRBs.

Design-a-trial: a rule-based decision support system for clinical trial design

The complexity of clinical research has meant that clinical trial protocols are often scientifically and ethically unsound. Trial designers often have limited statistical skills and experience in clinical research. This problem is exacerbated in the academic arena, in which access to statistical expertise is limited. Design-a-Trial (DaT) is an expert system that assists trial designers in designing and planning clinical trials. The system is developed in Visual Basic.NET and Prolog, and is due for commercial release in September 2003. The main aim of DaT is to help trial designers with limited statistical and research experience to design scientifically and ethically sound trials. It also serves as a checklist for the more experienced designers and can potentially be used to assist in the training of new clinical researchers.