Improving Clinical Trial Participant Tracking Tools Using Knowledge-anchored Design Methodologies.
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ABSTRACT:
SUBMITTER: Payne PR
PROVIDER: S-EPMC3225206 | biostudies-other | 2010
REPOSITORIES: biostudies-other
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Project description:BackgroundCurrently, the most promising therapies for Duchenne muscular dystrophy (DMD) are exon skipping and stop codon read-through, two strategies aimed at restoring the expression of dystrophin. A phase 3 clinical trial with drisapersen, a drug designed to induce exon 51-skipping, has failed to show significant improvement of the primary outcome measure, the six-minute walk test.DiscussionHere, we review some key points that should be considered when designing clinical trials for these new therapies. First, younger patients have more functional abilities and more muscle fibers to preserve than older patients and therefore are better subjects for trials designed to demonstrate the success of new treatments. Second, the inclusion of patients on corticosteroids both in the treatment and placebo groups is of concern because the positive effect of corticosteroids might mask the effect of the treatment being tested. Additionally, the reasonable expectation from these therapies is the slowing of disease progression rather than improvement. Therefore, the appropriate clinical endpoints are the prolongation of the ability to stand from the floor, climb stairs, and walk, not an increase in muscle strength or function. Hence, the time frames for the detection of new dystrophin, which occurs within months, and the ability to demonstrate a slowing of disease progression, which requires years, are strikingly different. Finally, placebo-controlled trials are difficult to manage if years of blindness are required to demonstrate a slowing of disease progression. Thus, accelerated/conditional approval for new therapies should be based on surrogate biochemical outcomes: the demonstration of de novo dystrophin production and of its beneficial effect on the functional recovery of muscle fiber. These data suggest that clinical trials for DMD patients must be adapted to the particular characteristics of the disease in order to demonstrate the expected positive effect of new treatments.
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Project description:BackgroundClinical trials are the primary mechanism for advancing clinical care and evidenced-based practice, yet challenges with the recruitment of participants for such trials are widely recognized as a major barrier to these types of studies. Data warehouses (DW) store large amounts of heterogenous clinical data that can be used to enhance recruitment practices, but multiple challenges exist when using a data warehouse for such activities, due to the manner of collection, management, integration, analysis, and dissemination of the data. A critical step in leveraging the DW for recruitment purposes is being able to match trial eligibility criteria to discrete and semi-structured data types in the data warehouse, though trial eligibility criteria tend to be written without concern for their computability. We present the multi-modal evaluation of a web-based tool that can be used for pre-screening patients for clinical trial eligibility and assess the ability of this tool to be practically used for clinical research pre-screening and recruitment.MethodsThe study used a validation study, usability testing, and a heuristic evaluation to evaluate and characterize the operational characteristics of the software as well as human factors affecting its use.ResultsClinical trials from the Division of Cardiology and the Department of Family Medicine were used for this multi-modal evaluation, which included a validation study, usability study, and a heuristic evaluation. From the results of the validation study, the software demonstrated a positive predictive value (PPV) of 54.12% and 0.7%, respectively, and a negative predictive value (NPV) of 73.3% and 87.5%, respectively, for two types of clinical trials. Heuristic principles concerning error prevention and documentation were characterized as the major usability issues during the heuristic evaluation.ConclusionsThis software is intended to provide an initial list of eligible patients to a clinical study coordinators, which provides a starting point for further eligibility screening by the coordinator. Because this software has a high "rule in" ability, meaning that it is able to remove patients who are not eligible for the study, the use of an automated tool built to leverage an existing enterprise DW can be beneficial to determining eligibility and facilitating clinical trial recruitment through pre-screening. While the results of this study are promising, further refinement and study of this and related approaches to automated eligibility screening, including comparison to other approaches and stakeholder perceptions, are needed and future studies are planned to address these needs.
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Project description:We consider why and how women track their menstrual cycles, examining their experiences to uncover design opportunities and extend the field's understanding of personal informatics tools. To understand menstrual cycle tracking practices, we collected and analyzed data from three sources: 2,000 reviews of popular menstrual tracking apps, a survey of 687 people, and follow-up interviews with 12 survey respondents. We find that women track their menstrual cycle for varied reasons that include remembering and predicting their period as well as informing conversations with healthcare providers. Participants described six methods of tracking their menstrual cycles, including use of technology, awareness of their premenstrual physiological states, and simply remembering. Although women find apps and calendars helpful, these methods are ineffective when predictions of future menstrual cycles are inaccurate. Designs can create feelings of exclusion for gender and sexual minorities. Existing apps also generally fail to consider life stages that women experience, including young adulthood, pregnancy, and menopause. Our findings encourage expanding the field's conceptions of personal informatics.
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Project description:BackgroundAnaemia is common in chronic kidney disease (CKD) and assessment of the risks and benefits of new therapies is important.MethodsThe Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3-5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8-10 g/dL or receiving ESAs with screening Hb of 8-12 g/dL. Participants were randomized to daprodustat or darbepoetin alfa (1:1) in an open-label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28-52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials.ResultsOverall, 3872 patients were randomized from 39 countries (median age 67 years, 56% female, 56% White, 27% Asian and 10% Black). The median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and estimated glomerular filtration rate was 18 mL/min/1.73 m2. Among randomized patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin-angiotensin system blockers, 55% were taking statins and 49% were taking oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials.ConclusionASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis.
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Project description:Clinical trial oversight is a critical element that ensures the protection of research participants and integrity of the data collected. The trial sponsor, a local Institutional Review Board, and independent monitoring committees all contribute with complementary but overlapping responsibilities. Consistency among these groups is essential for the smooth conduct of a clinical trial but may be challenging in resource-limited settings (RLS). Capacity building and training for RLS may improve clinical trials oversight and ultimately medical management. In this article, we review the components necessary for optimal clinical trial oversight and the issues that arise in the RLS, with some suggested strategies for improvement.
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Project description:Background:Positive impacts of quality improvement initiatives on health care and services have not been substantial. Knowledge translation (KT) strategies (tools, products and interventions) strive to facilitate the uptake of knowledge thereby the potential to improve care, but there is little guidance on how to develop them. Existing KT guidance or planning tools fall short in operationalizing all aspects of KT practice activities conducted by knowledge users (researchers, clinicians, patients, decision-makers), and most do not consider their variable needs or to deliver recommendations that are most relevant and useful for them. Methods:We conducted a 3-phase study. In phase 1, we used several sources to develop a conceptual framework for creating optimized Knowledge-activated Tools (KaT) (consultation with our integrated KT team, the use of existing KT models and frameworks, findings of a systematic review of multimorbidity interventions and a literature review and document analysis on existing KT guidance tools). In phase 2, we invited KT experts to participate in a Delphi study to refine and evaluate the conceptual KaT framework. In phase 3, we administered an online survey to knowledge users (researchers, clinicians, decision-makers, trainees) to evaluate the potential usefulness of an online mock-up version of the KaT framework. Results:We developed the conceptual KaT framework, and iteratively refined it with 35 KT experts in a 3-round Delphi study. The final framework represents the blueprint for what is needed to create KT strategies. Feedback from 201 researcher, clinician, decision-maker and trainee knowledge users on the potential need and usefulness of an online, interactive version of KaT indicated that they liked the idea of it (mean score 4.36 on a 5-point Likert scale) and its proposed features (mean score range 4.30-4.79). Conclusions:Our findings suggest that mostly Canadian KT experts and knowledge users perceived the KaT framework and the future development of an online, interactive version to be important and needed. We anticipate that the KaT framework will provide clarity for knowledge users about how to identify their KT needs and what activities can address these needs, and to help streamline the process of these activities to facilitate efficient uptake of knowledge.
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2020-07-09 | GSE144604 | GEO
Project description:Clinical trial and epidemiological studies need high quality biospecimens from a representative sample of participants to investigate genetic influences on treatment response and disease. Obtaining blood biospecimens presents logistical and financial challenges. As a result, saliva biospecimen collection is becoming more frequent because of the ease of collection and lower cost. This article describes an assessment of saliva biospecimen samples collected through the mail, trial participant demographic and behavioral characteristics, and their association with saliva and DNA quantity and quality.Saliva biospecimens were collected using the Oragene(R) DNA Self-Collection Kits from participants in a National Cancer Institute funded smoking cessation trial. Saliva biospecimens from 565 individuals were visually inspected for clarity prior to and after DNA extraction. DNA samples were then quantified by UV absorbance, PicoGreen(R), and qPCR. Genotyping was performed on 11 SNPs using TaqMan(R) SNP assays and two VNTR assays. Univariate, correlation, and analysis of variance analyses were conducted to observe the relationship between saliva sample and participant characteristics.The biospecimen kit return rate was 58.5% among those invited to participate (n = 967) and 47.1% among all possible COMPASS participants (n = 1202). Significant gender differences were observed with males providing larger saliva volume (4.7 vs. 4.5 ml, p = 0.019), samples that were more likely to be judged as cloudy (39.5% vs. 24.9%, p < 0.001), and samples with greater DNA yield as measured by UV (190.0 vs. 138.5, p = 0.002), but reduced % human DNA content (73.2 vs. 77.6 p = 0.005) than females. Other participant characteristics (age, self-identified ethnicity, baseline cigarettes per day) were associated with saliva clarity. Saliva volume and saliva and DNA clarity were positively correlated with total DNA yield by all three quantification measurements (all r > 0.21, P < 0.001), but negatively correlated with % human DNA content (saliva volume r = -0.148 and all P < 0.010). Genotyping completion rate was not influenced by saliva or DNA clarity.Findings from this study show that demographic and behavioral characteristics of smoking cessation trial participants have significant associations with saliva and DNA metrics, but not with the performance of TaqMan(R) SNP or VNTR genotyping assays.COMPASS; registered as NCT00301145 at clinicaltrials.gov.
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