Clinical Trials Update 2014: Year in Review

This section of Headache annually reviews the status of recently completed and ongoing major clinical trials involving common headache disorders. The review will focus on multicenter trials of new therapies as well as novel formulations of previously approved therapeutics. Table 1 summarizes the major therapeutic headache trials that were ongoing at the end of 2014, according to data obtained from both the “ClinicalTrials.Gov” website and from corporate press releases and presentations.     

Research Fundamentals: Statistical Considerations in Research Design: A Simple Person's Approach

A basic understanding of statistical methodology is essential, both for designing quality research projects and for evaluating the medical literature. Careful statistical planning, including the selection of study endpoints, the determination of the required sample size, and the selection of statistical tests to be used in the data analysis, is important to ensure a successful research project. The purpose of this article is to provide a basic review of statistical terms and methods for both the researcher and the clinician, as well as to clarify questions that need to be answered prior to embarking on an experimental study. The advantages of collaborating with statistical consultants, and some guidelines for such collaborations, are discussed as well.     

电话传输心电图监测系统的临床应用分析

目的:通过回顾性分析我院794例运用电话传输心电监护系统患者的监测情况,总结分析TTM系统在临床应用中的价值和作用。方法:运用自行研制开发的XDJ系列电话心电传输系统对794例监测对象进行了3080次远程传输,对急症患者予以现场急救指导。结果:检出各种心律失常和心肌缺血2180例次,总的阳性检出率70.8%。其中发现高危情况95例次,均由现场指导抢救解决。结论:TTM系统适合于对各种心脏病患者或高危人群进行有效的院外监测,有利于预防各种心血管严重事件及心脏性猝死的发生,降低死亡率。     

What Industry Wants: An Empirical Analysis of Health Informatics Job Postings

Objectives  To describe the education, experience, skills, and knowledge required for health informatics jobs in the United States. Methods  Health informatics job postings ( n  = 206) from Indeed.com on April 14, 2020 were analyzed in an empirical analysis, with the abstraction of attributes relating to requirements for average years and types of experience, minimum and desired education, licensure, certification, and informatics skills. Results  A large percentage (76.2%) of posts were for clinical informaticians, with 62.1% of posts requiring a minimum of a bachelor''s education. Registered nurse (RN) licensure was required for 40.8% of posts, and only 7.3% required formal education in health informatics. The average experience overall was 1.6 years (standard deviation = 2.2), with bachelor''s and master''s education levels increasing mean experience to 3.5 and 5.8 years, respectively. Electronic health record support, training, and other clinical systems were the most sought-after skills. Conclusion  This cross-sectional study revealed the importance of a clinical background as an entree into health informatics positions, with RN licensure and clinical experience as common requirements. The finding that informatics-specific graduate education was rarely required may indicate that there is a lack of alignment between academia and industry, with practical experience preferred over specific curricular components. Clarity and shared understanding of terms across academia and industry are needed for defining and advancing the preparation for and practice of health informatics.     

Optimizing Clinical Monitoring Tools to Enhance Patient Review by Pharmacists

Background  The Clinical Monitoring List (CML) is a real-time scoring system and intervention tool used by Mayo Clinic pharmacists caring for hospitalized patients. Objective  The study aimed to describe the iterative development and implementation of pharmacist clinical monitoring tools within the electronic health record at a multicampus health system enterprise. Methods  Between October 2018 and January 2019, pharmacists across the enterprise were surveyed to determine opportunities and gaps in CML functionality. Responses were received from 39% ( n  = 162) of actively staffing inpatient pharmacists. Survey responses identified three main gaps in CML functionality: (1) the desire for automated checklists of tasks, (2) additional rule logic closely aligning with clinical practice guidelines, and (3) the ability to dismiss and defer rules. The failure mode and effect analysis were used to assess risk areas within the CML. To address identified gaps, two A/B testing pilots were undertaken. The first pilot analyzed the effect of updated CML rule logic on pharmacist satisfaction in the domains of automated checklists and guideline alignment. The second pilot assessed the utility of a Clinical Monitoring Navigator (CMN) functioning in conjunction with the CML to display rules with selections to dismiss or defer rules until a user-specified date. The CMN is a workspace to guide clinical end user workflows; permitting the review and actions to be completed within one screen using EHR functionality. Results  A total of 27 pharmacists across a broad range of practice specialties were selected for two separate two-week pilot tests. Upon pilot completion, participants were surveyed to assess the effect of updates on performance gaps. Conclusion  Findings from the enterprise-wide survey and A/B pilot tests were used to inform final build decisions and planned enterprise-wide updated CML and CMN launch. This project serves as an example of the utility of end-user feedback and pilot testing to inform project decisions, optimize usability, and streamline build activities.     

Patient Engagement in Neurological Clinical Trials Design: A Conference Summary

Objectives

The conference objectives included educating patients and advocates about clinical trials, educating the clinical research community about patient perspectives on participating in clinical trial design, and identifying strategies to increase participation in clinical trial design for neurological disorders.

Design

Observations were noted during a 1‐day conference attended by patients, patient advocates, clinical trial staff, and investigators. The conference offered didactic sessions, small, and large group discussions.

Participants

Conference participants were patients, patient advocates, clinical trial staff, students, and investigators interested in engaging patients in clinical trial design for neurological disorders.

Measures

Conference participants were asked to consider lessons learned that could increase patient engagement in clinical trial design.

Results

We found that there is growing interest in including patients in the design of clinical trials for neurological disorders. Several themes emerged on how to move forward: networking; the multifaceted roles of advocates in research; training and education; creating patient–researcher partnerships; and clinical trials regulation issues.

Conclusions

The conference provided a forum for dialogue regarding stakeholder engagement in the design of clinical trials for neurological disorders. This experience provides a template for replication and dissemination of this conference and informs next steps to accelerate the pathway from dialogue to action.     

Psychophysiological and MMPI Personality Assessment of Headaches: An Integrative Approach

SYNOPSIS
Multiple psychophysiological measures and personality assessment techniques were combined to facilitate the diagnosis of headache type and improve upon existing methodology. Twenty-four migraine, 24 chronic tension headache patients, and 24 normal age- and gender-matched controls were assessed with bilateral measures of frontalis and occipitalis EMG and blood volume pulse. All subjects completed the MMPI. Results suggest that headache subjects could be differentiated on baseline heart rates and MMPI scales 1,2,3, and 7. Only one physiological measure served as an index of psychological distress, suggesting issues of an interaction between psychophysiological and personality variables, as well as the chronicity of the headache.     

Tracking the Pharmaceutical Pipeline: Clinical Trials and Global Disease Burden

Aggregate data about pharmaceutical research and development (R&D) tend to examine Phase III trials. Hence, there are few published data about investigational drugs in earlier phases of clinical development that might fail. It is also unclear how well R&D corresponds to disease burden. We track the pharmaceutical pipeline using data from industry publications that provide otherwise unreported information about industry‐sponsored clinical trials. The sample includes 2,477 unique drug entities in 4,182 clinical trials. The majority of drugs targeted neoplasms (26.20%), neurological diseases/diseases of the sense organs (13.48%), infectious and parasitic diseases (10.5%), and endocrine, metabolic, nutrition, and immunity disorders (9.45%). Less than 6% of drugs targeted diseases of the circulatory system, which represent the most prevalent causes of global mortality. Detailing the pharmaceutical pipeline, our findings suggest that pharmaceutical development does not adequately address global disease burden. Future research on the under‐reported details of Phase I and II clinical trials is needed to understand how the industry operates and how its resource‐allocation matches global health concerns.     

Challenges in Implementing Hospice Clinical Trials: Preserving Scientific Integrity While Facing Change

Background/AimsNumerous changes can occur between the original design plans for clinical trials, the submission of funding proposals, and the implementation of the clinical trial. In the hospice setting, environmental changes can present significant obstacles, which require changes to the original plan designs, recruitment, and staffing. The purpose of the study was to share lessons and problem-solving strategies that can assist in future hospice trials.MethodsThis study uses one hospice clinical trial as an exemplar to demonstrate challenges for clinical trial research in this setting. Using preliminary data collected during the first months of a trial, the research team details the many ways their current protocol reflects changes from the originally proposed plans. Experiences are used as an exemplar to address the following questions: 1) How do research environments change between the initial submission of a funding proposal and the eventual award? 2) How can investigators maintain the integrity of the research and accommodate unexpected changes in the research environment?ResultsThe changing environment within the hospice setting required design, sampling, and recruitment changes within the first year. The decision-making process resulted in a stronger design with greater generalization. As a result of necessary protocol changes, the study results are positioned to be translational following the study conclusion.ConclusionResearchers would do well to review their protocol and statistics early in a clinical trial. They should be prepared for adjustments to accommodate market and environmental changes outside their control. Ongoing data monitoring, specifically related to recruitment, is advised.     

A Narrative Review of Clinical Decision Support for Inpatient Clinical Pharmacists

Objective  Increasingly, pharmacists provide team-based care that impacts patient care; however, the extent of recent clinical decision support (CDS), targeted to support the evolving roles of pharmacists, is unknown. Our objective was to evaluate the literature to understand the impact of clinical pharmacists using CDS. Methods  We searched MEDLINE, EMBASE, and Cochrane Central for randomized controlled trials, nonrandomized trials, and quasi-experimental studies which evaluated CDS tools that were developed for inpatient pharmacists as a target user. The primary outcome of our analysis was the impact of CDS on patient safety, quality use of medication, and quality of care. Outcomes were scored as positive, negative, or neutral. The secondary outcome was the proportion of CDS developed for tasks other than medication order verification. Study quality was assessed using the Newcastle–Ottawa Scale. Results  Of 4,365 potentially relevant articles, 15 were included. Five studies were randomized controlled trials. All included studies were rated as good quality. Of the studies evaluating inpatient pharmacists using a CDS tool, four showed significantly improved quality use of medications, four showed significantly improved patient safety, and three showed significantly improved quality of care. Six studies (40%) supported expanded roles of clinical pharmacists. Conclusion  These results suggest that CDS can support clinical inpatient pharmacists in preventing medication errors and optimizing pharmacotherapy. Moreover, an increasing number of CDS tools have been developed for pharmacists'' roles outside of order verification, whereby further supporting and establishing pharmacists as leaders in safe and effective pharmacotherapy.     

Recruitment and Retention of Patients into Emergency Medicine Clinical Trials

The emergency medicine (EM) and prehospital environments are unlike any other clinical environments and require special consideration to allow the successful implementation of clinical trials. This article reviews the specific issues involved in EM clinical trials and provides strategies from EM and non‐EM trials to maximize recruitment and retention. While the evidence supporting some of these strategies is deficient, addressing recruitment and retention issues with specific strategies will help researchers deal with these issues in their funding applications and in turn develop the necessary infrastructure to participate in EM clinical trials. ACADEMIC EMERGENCY MEDICINE 2010; 17:1104–1112 © 2010 by the Society for Academic Emergency Medicine     

Research Fundamentals: III. Elements of a Research Protocol for Clinical Trials

Abstract. A clinical trial is a powerful technique for evaluating the effectiveness of an experimental intervention. The initial stages of planning a clinical trial involve choosing and refining a research question, selecting a study design, and deciding on appropriate statistical tests and sample sizes. The success of the study depends upon how well these issues are thought out in advance, and how they can be put into practice. The protocol is the written document that allows the investigator to communicate details of how the research question will be answered. In the following article, the basic components of the research protocol are described. Issues related to quality control, data entry, and pilot testing are discussed. This is the third in a series of research fundamental concept papers, written by members of the SAEM Research Committee.     

Update on Vaccination Clinical Trials for HPV-Related Disease

Background

Cervical cancer remains a major cause of cancer death in women worldwide. Moreover, human papillomavirus (HPV)-related disease of the urogenital tract (including preinvasive and invasive cervical, vaginal, vulvar, penile, and anal disease) remains a major cause of morbidity and mortality in the United States and internationally.

Objective

The goal of this article was to review the vaccines available as well as the major Phase III trials of the quadrivalent and bivalent vaccines for the prevention of HPV-related genital tract disease.

Methods

A literature search was performed through PubMed using the terms “HPV vaccination” and limited to clinical trials over the last 6 years. The most relevant and largest scale trials were included in this report.

Results

Prophylactic vaccination has emerged as an important tool that holds promise in decreasing the burden of HPV disease. However, HPV vaccination is known to be largely type-specific. Vaccination is most effective when administered at a younger age and before sexual activity and exposure to HPV. Large trials have been conducted and show efficacy of both the bivalent (HPV types 16 and 18) and quadrivalent (HPV types 6, 11, 16, and 18) vaccine in the prevention of preinvasive lesions and infection with these HPV types.

Conclusions

Future directions include development of more affordable vaccines with extended HPV-type coverage as well as implementation of feasible worldwide vaccination programs.     

Emergency Medicine Leadership in Industry-sponsored Clinical Trials

OBJECTIVE: To identify and characterize emergency medicine (EM) researchers who, since 1990, have served on a steering committee (SC) or as overall principal investigator (PI) of an industry-sponsored, multicenter clinical trial involving a pharmaceutical or device. METHODS: North American EM research directors (RDs) and other prominent EM investigators (for those hospitals without a RD) were identified from eight sources, including the Society for Academic Emergency Medicine RD Interest Group and the Multicenter Airway Research Collaboration (MARC) database. The identified investigators were sent a screening survey requesting information regarding industry-sponsored clinical research at their site. The individual EM investigators identified by this screening survey were then interviewed by telephone (validation survey) to further explore their leadership experience in industry-sponsored clinical trials. RESULTS: Of 153 identified RDs and prominent EM researchers, 138 responded to the screening survey (90% response rate). Eighty-five EM investigators reportedly had served on a SC or as overall PI for an industry-sponsored clinical trial. Of these 85 North American EM investigators, 77 were available for a structured telephone interview (91% response rate). Although 41 (53%) of the investigators confirmed their leadership role, 36 (47%) had not served in either role. Among the 41 confirmed investigators, 19 (25%) had served as a SC member, 10 (13%) had served as overall PI, and 12 (16%) had experience in both roles. Individual responses provided suggestions for pursuing such leadership positions. CONCLUSIONS: These data suggest the opportunity to expand EM leadership in industry-sponsored clinical trials and demonstrate the need for validation of reports obtained by a departmental research contact. The suggestions from EM researchers who have attained these leadership roles may provide strategies for investigators interested in pursuing these positions.     

Oxygraphy: An Unexplored Perioperative Monitoring Modality

Capnography waveforms and capnometry are useful perioperative monitoring tools. The paramagnetic oxygen analyzers incorporated in many clinical monitoring systems estimate oxygen concentration in the breathing circuit during various phases of ventilation. The oxygen concentration is plotted as a real-time waveform and displayed as an oxygraph. However, the clinical utility of oxygraphy is under evaluated. We are reporting four different clinical scenarios in neurosurgical patients, wherein the information yielded by oxygraphy were either not available on the capnograph or were revealed in a more promising way on the oxygraph than on the capnograph. A real-time oxygraphy waveform has four phases similar to a capnograph, although displayed in a reverse manner. Oxygraphy was useful in our patient to determine the adequacy of preoxygenation. Airway complications and unwanted neuromuscular recovery can be detected earlier by oxygraphy compared to capnography. The oxygraphy peak-to-baseline scale difference can be compressed to as low as to 6% of oxygen concentration. When the peak-to-baseline scale difference is 6 mmHg, the oxygraph becomes sensitive to even minute changes in respiratory flow characteristics. Oxygraphy may have a potential role in clinical monitoring. Gadhinglajkar S, Sreedhar R, Unnikrishnan KP. Oxygraphy: an unexplored Perioperative monitoring modality.     

Assessing the Impact of the NIH CTSA Program on Institutionally Sponsored Clinical Trials

Objective

To assess the impact of the NIH CTSA program on patient enrollment in clinical trials sponsored/collaborated by CTSA consortium institutions.

Material and Methods

Using publicly available clinical trial data at ClinicalTrials.gov, we identify positive trend changes in the number of patients enrolled in clinical trials performed at CTSA consortium institutions over the years before and after their respective CTSA award dates. CTSA consortium institutions were matched with similar non‐CTSA institutions.

Results

As compared to matched non‐CTSA institutions CTSA consortium sites noted an increase in patient enrollment after the CTSA awards. In particular, we detected a change‐point, where a new enrollment trend emerged, 338 days after the CTSA award. No such trend was noted over the same period in the non‐CTSA institutions.

Conclusion

Our analysis provides evidence that the NIH CTSA funding program made a positive impact on patient enrollment.