An eye on the dog as the scientist's best friend for translational research in ophthalmology: Focus on the ocular surface

Preclinical animal studies provide valuable opportunities to better understand human diseases and contribute to major advances in medicine. This review provides a comprehensive overview of ocular parameters in humans and selected animals, with a focus on the ocular surface, detailing species differences in ocular surface anatomy, physiology, tear film dynamics and tear film composition. We describe major pitfalls that tremendously limit the translational potential of traditional laboratory animals (i.e., rabbits, mice, and rats) in ophthalmic research, and highlight the benefits of integrating companion dogs with clinical analogues to human diseases into preclinical pharmacology studies. This One Health approach can help accelerate and improve the framework in which ophthalmic research is translated to the human clinic. Studies can be conducted in canine subjects with naturally occurring or noninvasively induced ocular surface disorders (e.g., dry eye disease, conjunctivitis), reviewed herein, and tear fluid can be easily retrieved from canine eyes for various bioanalytical purposes. In this review, we discuss common tear collection methods, including capillary tubes and Schirmer tear strips, and provide guidelines for tear sampling and extraction to improve the reliability of analyte quantification (drugs, proteins, others).     

Participation in Clinical Research: Perspectives of Adult Patients and Parents of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

Despite major improvements over the past several decades, many patients undergoing hematopoietic stem cell transplantations (HSCT) continue to suffer from significant treatment-related morbidity and mortality. Clinical research studies (trials) have been integral to advancing the standard of care in HSCT. However, 1 of the biggest challenges with clinical trials is the low participation rate. Although barriers to participation in cancer clinical trials have been previously explored, studies specific to HSCT are lacking. The current study was undertaken to examine the knowledge, attitudes, and perceptions of HSCT patients regarding clinical trials. As members of focus groups, participants responded to open-ended questions that assessed factors influencing decision-making about HSCT clinical trials. Suggestions for improvements in the recruitment process were also solicited among participants. Seventeen adult HSCT patients and 6 parents of pediatric HSCT patients participated in the study. The median age was 56 years (range, 18 to 70) and 44 years (range, 28 to 54) for adult patients and parents, respectively. Participants universally indicated that too much information was provided within the informed consents and they were intimidated by the medical and legal language. Despite the large amount of information provided to them at the time of study enrollment, the participants had limited knowledge retention and recall of study details. Nevertheless, participants reported overall positive experiences with clinical trial participation and many would readily choose to participate again. A common concern among participants was the uncertainty of study outcome and general lack of feedback about results at the end of the study. Participants suggested that investigators provide more condensed and easier to understand informed consents and follow-up of study findings. These findings could be used to help guide the development of improved consent documents and enhanced participation in research studies, thereby affecting the future design of HSCT research protocols.     

How Can Research Keep Up With eHealth? Ten Strategies for Increasing the Timeliness and Usefulness of eHealth Research

Background

eHealth interventions appear and change so quickly that they challenge the way we conduct research. By the time a randomized trial of a new intervention is published, technological improvements and clinical discoveries may make the intervention dated and unappealing. This and the spate of health-related apps and websites may lead consumers, patients, and caregivers to use interventions that lack evidence of efficacy.

Objective

This paper aims to offer strategies for increasing the speed and usefulness of eHealth research.

Methods

The paper describes two types of strategies based on the authors’ own research and the research literature: those that improve the efficiency of eHealth research, and those that improve its quality.

Results

Efficiency strategies include: (1) think small: conduct small studies that can target discrete but significant questions and thereby speed knowledge acquisition; (2) use efficient designs: use such methods as fractional-factorial and quasi-experimental designs and surrogate endpoints, and experimentally modify and evaluate interventions and delivery systems already in use; (3) study universals: focus on timeless behavioral, psychological, and cognitive principles and systems; (4) anticipate the next big thing: listen to voices outside normal practice and connect different perspectives for new insights; (5) improve information delivery systems: researchers should apply their communications expertise to enhance inter-researcher communication, which could synergistically accelerate progress and capitalize upon the availability of “big data”; and (6) develop models, including mediators and moderators: valid models are remarkably generative, and tests of moderation and mediation should elucidate boundary conditions of effects and treatment mechanisms. Quality strategies include: (1) continuous quality improvement: researchers need to borrow engineering practices such as the continuous enhancement of interventions to incorporate clinical and technological progress; (2) help consumers identify quality: consumers, clinicians, and others all need to easily identify quality, suggesting the need to efficiently and publicly index intervention quality; (3) reduce the costs of care: concern with health care costs can drive intervention adoption and use and lead to novel intervention effects (eg, reduced falls in the elderly); and (4) deeply understand users: a rigorous evaluation of the consumer’s needs is a key starting point for intervention development.

Conclusions

The challenges of distinguishing and distributing scientifically validated interventions are formidable. The strategies described are meant to spur discussion and further thinking, which are important, given the potential of eHealth interventions to help patients and families.     

Using Online Social Media for Recruitment of Human Immunodeficiency Virus-Positive Participants: A Cross-Sectional Survey

Background

There are many challenges in recruiting and engaging participants when conducting research, especially with HIV-positive individuals. Some of these challenges include geographical barriers, insufficient time and financial resources, and perceived HIV-related stigma.

Objective

This paper describes the methodology of a recruitment approach that capitalized on existing online social media venues and other Internet resources in an attempt to overcome some of these barriers to research recruitment and retention.

Methods

From May through August 2013, a campaign approach using a combination of online social media, non-financial incentives, and Web-based survey software was implemented to advertise, recruit, and retain participants, and collect data for a survey study with a limited budget.

Results

Approximately US $5,000 was spent with a research staff designated at 20% of full-time effort, yielding 2034 survey clicks, 1404 of which met the inclusion criteria and initiated the survey, for an average cost of US $3.56 per survey initiation. A total of 1221 individuals completed the survey, yielding 86.97% retention.

Conclusions

These data indicate that online recruitment is a feasible and efficient tool that can be further enhanced by sophisticated online data collection software and the addition of non-financial incentives.     

From expert-derived user needs to user-perceived ease of use and usefulness: A two-phase mixed-methods evaluation framework

Underspecified user needs and frequent lack of a gold standard reference are typical barriers to technology evaluation. To address this problem, this paper presents a two-phase evaluation framework involving usability experts (phase 1) and end-users (phase 2). In phase 1, a cross-system functionality alignment between expert-derived user needs and system functions was performed to inform the choice of “the best available” comparison system to enable a cognitive walkthrough in phase 1 and a comparative effectiveness evaluation in phase 2. During phase 2, five quantitative and qualitative evaluation methods are mixed to assess usability: time-motion analysis, software log, questionnaires – System Usability Scale and the Unified Theory of Acceptance of Use of Technology, think-aloud protocols, and unstructured interviews. Each method contributes data for a unique measure (e.g., time motion analysis contributes task-completion-time; software log contributes action transition frequency). The measures are triangulated to yield complementary insights regarding user-perceived ease-of-use, functionality integration, anxiety during use, and workflow impact. To illustrate its use, we applied this framework in a formative evaluation of a software called Integrated Model for Patient Care and Clinical Trials (IMPACT). We conclude that this mixed-methods evaluation framework enables an integrated assessment of user needs satisfaction and user-perceived usefulness and usability of a novel design. This evaluation framework effectively bridges the gap between co-evolving user needs and technology designs during iterative prototyping and is particularly useful when it is difficult for users to articulate their needs for technology support due to the lack of a baseline.     

The Ontology of Clinical Research (OCRe): An informatics foundation for the science of clinical research

To date, the scientific process for generating, interpreting, and applying knowledge has received less informatics attention than operational processes for conducting clinical studies. The activities of these scientific processes – the science of clinical research – are centered on the study protocol, which is the abstract representation of the scientific design of a clinical study. The Ontology of Clinical Research (OCRe) is an OWL 2 model of the entities and relationships of study design protocols for the purpose of computationally supporting the design and analysis of human studies. OCRe’s modeling is independent of any specific study design or clinical domain. It includes a study design typology and a specialized module called ERGO Annotation for capturing the meaning of eligibility criteria. In this paper, we describe the key informatics use cases of each phase of a study’s scientific lifecycle, present OCRe and the principles behind its modeling, and describe applications of OCRe and associated technologies to a range of clinical research use cases. OCRe captures the central semantics that underlies the scientific processes of clinical research and can serve as an informatics foundation for supporting the entire range of knowledge activities that constitute the science of clinical research.