Web-based adaptive training simulator system for cardiac life support

OBJECTIVE: We introduce a web-based adaptive training simulator system to exercise cardiopulmonary resuscitation skills. Our purpose is to provide emergency physicians with an additional training tool for cardiac life support clinical cases, by integrating an adaptive learning environment with a web-based case simulator. METHODS AND MATERIALS: Adaptive systems reflect some features of the user in the user model and apply this model to adapt various visible aspects of the system to the user. Our system follows a stage-based learning model with several steps to personalize student learning. First, students learn the theory and content of life support and take computerized tests to evaluate their declarative knowledge of these areas. Second, they practice with clinical case examples and complete an exam at the appropriate level of difficulty to assess their practical knowledge. Finally, they train with additional clinical cases. RESULTS AND CONCLUSION: In order to evaluate the usefulness of the system, we used it in two traditional advanced life support courses at the Jaen Hospital in Spain, as an additional and complementary tool within the course. Results show that the use of adaptation techniques can improve student performance.     

Predictive factors of telemedicine service acceptance and behavioral intention of physicians

PurposeDespite the proliferation of telemedicine technology, telemedicine service acceptance has been slow in actual healthcare settings. The purpose of this research is to develop a theoretical model for explaining the predictive factors influencing physicians’ willingness to use telemedicine technology to provide healthcare services.MethodsWe developed the Telemedicine Service Acceptance model based on the technology acceptance model (TAM) with the inclusion of three predictive constructs from the previously published telemedicine literature: (1) accessibility of medical records and of patients as clinical factors, (2) self-efficacy as an individual factor and (3) perceived incentives as regulatory factors. A survey was conducted, and structural equation modeling was applied to evaluate the empirical validity of the model and causal relationships within the model using the data collected from 183 physicians.ResultsOur results confirmed the validity of the original TAM constructs: the perceived usefulness of telemedicine directly impacted the behavioral intention to use it, and the perceived ease of use directly impacted both the perceived usefulness and the behavioral intention to use it. In addition, new predictive constructs were found to have ramifications on TAM variables: the accessibility of medical records and of patients directly impacted the perceived usefulness of telemedicine, self-efficacy had a significant positive effect on both the perceived ease of use and the perceived usefulness of telemedicine, and perceived incentives were found to be important with respect to the intention to use telemedicine technology.ConclusionsThis study demonstrated that the Telemedicine Service Acceptance model was feasible and could explain the acceptance of telemedicine services by physicians. These results identified important factors for increasing the involvement of physicians in telemedicine practice.     

Differential clinicopathological features in microsatellite instability-positive colorectal cancers depending on CIMP status

Microsatellite instability-positive (MSI+) colorectal cancers (CRCs) are divided into CpG island methylator phenotype-positive (CIMP+) and CpG island methylator phenotype-negative (CIMP−) tumors. The repertoire of inactivated genes in CIMP+/MSI+ CRCs overlaps with but is likely to differ from that of CIMP−/MSI+ CRCs. Because epigenotypic differences are likely to be manifested as phenotypic differences, CIMP+/MSI+ CRCs are expected to differ from CIMP−/MSI+ CRCs in some clinicopathological features. This study aimed to characterize both common and different features between the two subtypes. A total of 72 MSI+ CRCs were analyzed for their methylation status in eight CIMP panel markers using MethyLight assay. CIMP+/MSI+ and CIMP−/MSI+ CRCs were compared regarding clinicopathologic features and mutation in KRAS/BRAF. An independent set of MSI+ CRCs (n = 97) was analyzed for their relationship of CIMP+ status with clinical outcome. Eighteen cases (25%) were CIMP+, and this CIMP+ subtype was highly correlated with older age (P < 0.001). Polypoid gross appearance without ulceration was observed only in CIMP−/MSI+ CRCs (18.5%, P = 0.057). CIMP+/MSI+ CRCs were closely associated with poor differentiation, medullary appearance, signet ring cell appearance, and acinar-form appearance, whereas the CIMP−/MSI+ subtype was closely associated with intraglandular eosinophilic mucin and stratified nuclei (all P values <0.05). Patients with CIMP+/MSI+ CRCs showed worse overall survival than patients with CIMP−/MSI+ CRCs. Our results demonstrate heterogeneity in the clinicopathological features of MSI+ CRCs depending on CIMP status. The observation that CIMP+ and CIMP− subtypes showed different clinical behaviors may provide a clue for establishing subtype-specific therapeutic strategies for these two subtypes.     

Usability study of clinical exome analysis software: Top lessons learned and recommendations

ObjectivesNew DNA sequencing technologies have revolutionized the search for genetic disruptions. Targeted sequencing of all protein coding regions of the genome, called exome analysis, is actively used in research-oriented genetics clinics, with the transition to exomes as a standard procedure underway. This transition is challenging; identification of potentially causal mutation(s) amongst ∼10⁶ variants requires specialized computation in combination with expert assessment. This study analyzes the usability of user interfaces for clinical exome analysis software. There are two study objectives: (1) To ascertain the key features of successful user interfaces for clinical exome analysis software based on the perspective of expert clinical geneticists, (2) To assess user-system interactions in order to reveal strengths and weaknesses of existing software, inform future design, and accelerate the clinical uptake of exome analysis.MethodsSurveys, interviews, and cognitive task analysis were performed for the assessment of two next-generation exome sequence analysis software packages. The subjects included ten clinical geneticists who interacted with the software packages using the “think aloud” method. Subjects’ interactions with the software were recorded in their clinical office within an urban research and teaching hospital. All major user interface events (from the user interactions with the packages) were time-stamped and annotated with coding categories to identify usability issues in order to characterize desired features and deficiencies in the user experience.ResultsWe detected 193 usability issues, the majority of which concern interface layout and navigation, and the resolution of reports. Our study highlights gaps in specific software features typical within exome analysis. The clinicians perform best when the flow of the system is structured into well-defined yet customizable layers for incorporation within the clinical workflow. The results highlight opportunities to dramatically accelerate clinician analysis and interpretation of patient genomic data.ConclusionWe present the first application of usability methods to evaluate software interfaces in the context of exome analysis. Our results highlight how the study of user responses can lead to identification of usability issues and challenges and reveal software reengineering opportunities for improving clinical next-generation sequencing analysis. While the evaluation focused on two distinctive software tools, the results are general and should inform active and future software development for genome analysis software. As large-scale genome analysis becomes increasingly common in healthcare, it is critical that efficient and effective software interfaces are provided to accelerate clinical adoption of the technology. Implications for improved design of such applications are discussed.     

Prognostic implications of CpG island hypermethylator phenotype in colorectal cancers

CpG island methylator phenotype (CIMP) refers to a subset of colorectal cancers (CRCs) that are characterized by concordant hypermethylation of multiple CpG island loci. CIMP+ CRCs have peculiar clinicopathological features. However, controversy exists over prognostic implications of CIMP in CRCs. We analyzed 320 cases of CRCs for their CIMP status using the MethyLight assay and determined clinicopathological features and prognostic implications of CIMP alone or in combination with microsatellite instability (MSI). With methylation of five or more markers among eight markers examined, CIMP+ tumors were significantly associated with female gender, proximal tumor location, poor differentiation, nodal metastasis, more advanced cancer, BRAF mutations, MSI, and poor prognosis (all P values <0.05). Ogino’s combined eight-marker panel outperformed the Ogino and the Laird five-marker panels in detecting these features. Of the four molecular subtypes generated by the combination of CIMP and MSI status, the CIMP+/MSI? subtype showed the worst clinical outcome (P?=?0.0003). However, poor prognosis of CIMP+/MSI? subtype was found to be attributed to BRAF mutation. In conclusion, the CIMP+/MSI? subtype tends to present with distinct clinicopathological and molecular features and shows the worst clinical outcome among the four molecular subtypes of CRCs.     

Nonverbal communication in doctor-elderly patient transactions (NDEPT): development of a tool

OBJECTIVE: There are several measurement tools to assess verbal dimensions in clinical encounters; in contrast, there is no established tool to evaluate physical nonverbal dimensions in geriatric encounters. The present paper describes the development of a tool to assess the physical context of exam rooms in doctor-older patient visits. METHOD: Salient features of the tool were derived from the medical literature and systematic observations of videotapes and refined during current research. RESULTS: The tool consists of two main dimensions of exam rooms: (1) physical dimensions comprising static and dynamic attributes that become operational through the spatial configuration and can influence the manifestation of (2) kinesic attributes. CONCLUSION: Details of the coding form and inter-rater reliability are presented. The usefulness of the tool is demonstrated through an analysis of 50 National Institute of Aging videotapes. Physicians in exam rooms with no desk in the interaction, no height difference and optimal interaction distance were observed to have greater eye contact and touch than physicians' in exam rooms with a desk, similar height difference and interaction distance. PRACTICE IMPLICATIONS: The tool can enable physicians to assess the spatial configuration of exam rooms (through Parts A and B) and thus facilitate the structuring of kinesic attributes (Part C).     

Physicians’ perspectives of adopting computer-assisted navigation in orthopedic surgery

ObjectivesUsing Computer-assisted orthopedic navigation surgery system (CAOS) has many advantages but is not mandatory to use during an orthopedic surgery. Therefore, opinions obtained from clinical orthopedists with this system are valuable. This paper integrates technology acceptance model and theory of planned behavior to examine the determinants of continued CAOS use to facilitate user management.MethodsOpinions from orthopedists who had used a CAOS for at least two years were collected through a cross-sectional survey to verify the research framework. Follow-up interviews with an expert panel based on their experiences of CAOS were conducted to reason the impacts of factors of the research framework.ResultsThe results show that factors of “perceived usefulness” and “facilitating condition” determine the intention to continue using CAOS, and “perceived usefulness” was driving by “complexity of task” and “social influence”. Additionally, support in practice from high-level managers had an influence on orthopedists’ satisfaction after using a CAOS.ConclusionsThe aging population is accompanied by the increasing requirements for medical care and medical care attendant expenses, especially in total knee replacement. More precision and improvements on survivorship of patients’ artificial joints are needed. This study facilitates suggestions in user management when encountering an obstacle in implementing a CAOS. Based on these findings, scientific and practical implications are then discussed.     

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.     

Preferences for self-management support: findings from a survey of diabetes patients in safety-net health systems

OBJECTIVE: We sought to identify interest in different modes of self-management support among diabetes patients cared for in public hospitals, and to assess whether demographic or disease-specific factors were associated with patient preferences. We explored the possible role of a perceived communication need in influencing interest in self-management support. METHODS: Telephone survey of a random sample of 796 English and Spanish-speaking diabetes patients (response rate 47%) recruited from four urban US public hospital systems. In multivariate models, we measured the association of race/ethnicity, primary language, self-reported health literacy, self-efficacy, and diabetes-related factors on patients' interest in three self-management support strategies (telephone support, group medical visits, and Internet-based support). We explored the extent to which patients believed that better communication with providers would improve their diabetes control, and whether this perception altered the relationship between patient factors and self-management support acceptance. RESULTS: Sixty-nine percent of respondents reported interest in telephone support, 55% in group medical visits, and 42% in Internet. Compared to Non-Hispanic Whites, Spanish-speaking Hispanics were more interested in telephone support (OR 3.45, 95% CI 1.97-6.05) and group medical visits (OR 2.45, 95% CI 1.49-4.02), but less interested in Internet self-management support (OR 0.56, 95% CI 0.33-0.93). African-Americans were more interested than Whites in all three self-management support strategies. Patients with limited self-reported health literacy were more likely to be interested in telephone support than those not reporting literacy deficits. Forty percent reported that their diabetes would be better controlled if they communicated better with their health care provider. This perceived communication benefit was independently associated with interest in self-management support (p<0.001), but its inclusion in models did not alter the strengths of the main associations between patient characteristics and self-management support preferences. CONCLUSION: Many diabetes patients in safety-net settings report an interest in receiving self-management support, but preferences for modes of delivery of self-management support vary by race/ethnicity, language proficiency, and self-reported health literacy. PRACTICE IMPLICATIONS: Public health systems should consider offering a range of self-management support services to meet the needs of their diverse patient populations. More broad dissemination and implementation of self-management support may help address the unmet need for better provider communication among diabetes patients in these settings.     

Understanding technology adoption in clinical care: clinician adoption behavior of a point-of-care reminder system

BACKGROUND: Evaluation studies of clinical decision support systems (CDSS) have tended to focus on assessments of system quality and clinical performance in a laboratory setting. Relatively few studies have used field trials to determine if CDSS are likely to be used in routine clinical settings and whether reminders generated are likely to be acted upon by end-users. Moreover, such studies when performed tend not to identify distinct user groups, nor to classify user feedback. AIM: To assess medical residents' acceptance and adoption of a clinical reminder system for chronic disease and preventive care management and to use expressed preferences for system attributes and functionality as a basis for system re-engineering. DESIGN OF STUDY: Longitudinal, correlational study using a novel developmental trajectory analysis (DTA) statistical method, followed by a qualitative analysis based on user satisfaction surveys and field interviews. SETTING: An ambulatory primary care clinic of an urban teaching hospital offering comprehensive healthcare services. 41 medical residents used a CDSS over 10 months in their daily practice. Use of this system was strongly recommended but not mandatory. METHODS: A group-based, semi-parametric statistical modeling method to identify distinct groups, with distinct usage trajectories, followed by qualitative instruments of usability and satisfaction surveys and structured interviews to validate insights derived from usage trajectories. RESULTS: Quantitative analysis delineates three types of user adoption behavior: "light", "moderate" and "heavy" usage. Qualitative analysis reveals that clinicians of distinct types tend to exhibit views of the system consistent with their demonstrated adoption behavior. Drawbacks in the design of the CDSS identified by users of all types (in different ways) motivate a redesign based on current physician workflows. CONCLUSION: We conclude that this mixed methodology has considerable promise to provide new insights into system usability and adoption issues that may benefit clinical decision support systems as well as information systems more generally.     

Modelling assistive technology adoption for people with dementia

PurposeAssistive technologies have been identified as a potential solution for the provision of elderly care. Such technologies have in general the capacity to enhance the quality of life and increase the level of independence among their users. Nevertheless, the acceptance of these technologies is crucial to their success. Generally speaking, the elderly are not well-disposed to technologies and have limited experience; these factors contribute towards limiting the widespread acceptance of technology. It is therefore important to evaluate the potential success of technologies prior to their deployment.Materials and methodsThe research described in this paper builds upon our previous work on modelling adoption of assistive technology, in the form of cognitive prosthetics such as reminder apps and aims at identifying a refined sub-set of features which offer improved accuracy in predicting technology adoption. Consequently, in this paper, an adoption model is built using a set of features extracted from a user’s background to minimise the likelihood of non-adoption. The work is based on analysis of data from the Cache County Study on Memory and Aging (CCSMA) with 31 features covering a range of age, gender, education and details of health condition. In the process of modelling adoption, feature selection and feature reduction is carried out followed by identifying the best classification models.FindingsWith the reduced set of labelled features the technology adoption model built achieved an average prediction accuracy of 92.48% when tested on 173 participants.ConclusionsWe conclude that modelling user adoption from a range of parameters such as physical, environmental and social perspectives is beneficial in recommending a technology to a particular user based on their profile.     

A study of the influence of task familiarity on user behaviors and performance with a MeSH term suggestion interface for PubMed bibliographic search

PurposePrevious research has shown that information seekers in biomedical domain need more support in formulating their queries. A user study was conducted to evaluate the effectiveness of a metadata based query suggestion interface for PubMed bibliographic search. The study also investigated the impact of search task familiarity on search behaviors and the effectiveness of the interface.MethodsA real user, user search request and real system approach was used for the study. Unlike tradition IR evaluation, where assigned tasks were used, the participants were asked to search requests of their own. Forty-four researchers in Health Sciences participated in the evaluation – each conducted two research requests of their own, alternately with the proposed interface and the PubMed baseline. Several performance criteria were measured to assess the potential benefits of the experimental interface, including users’ assessment of their original and eventual queries, the perceived usefulness of the interfaces, satisfaction with the search results, and the average relevance score of the saved records.ResultsThe results show that, when searching for an unfamiliar topic, users were more likely to change their queries, indicating the effect of familiarity on search behaviors. The results also show that the interface scored higher on several of the performance criteria, such as the “goodness” of the queries, perceived usefulness, and user satisfaction. Furthermore, in line with our hypothesis, the proposed interface was relatively more effective when less familiar search requests were attempted.ConclusionsResults indicate that there is a selective compatibility between search familiarity and search interface. One implication of the research for system evaluation is the importance of taking into consideration task familiarity when assessing the effectiveness of interactive IR systems.     

Evaluation of a computerized contraceptive decision aid for adolescent patients

Recent efforts to involve patients more actively in therapeutic decisions have suggested the relevance of computer-based interventions at clinic visits. This paper presents a longitudinal, experimental study evaluating a computer-based contraceptive decision aid in Chicago and Madison family planning clinic visits. Patient interviews at three time points evaluated patient acceptance by and program impact on 949 young women. Both Chicago and Madison patients reported high acceptance. The program resulted in improved short-term knowledge and confidence in oral contraceptive (OC) efficacy for Chicago and Madison patients. In addition, compared to their control group, Madison experimental group patients had higher OC knowledge 1 year after the initial visit and a trend for fewer pregnancies (P < 0.074). Compared to their control group, a higher percent of the Chicago experimental group patients adopted OC's after stating their intention to do so at the initial visit. Exposure to the computer program had no observable impact on the number of months on the oral contraceptive for Chicago or Madison patients. Overall findings suggest the usefulness of informatics tools as a supplement to patient-provider interactions.     

Near-diploid and near-triploid human sporadic colorectal adenocarcinomas differ for KRAS2 and TP53 mutational status

Mutations of the KRAS2 protoncogene and inactivation of the TP53 oncosuppressor gene have been suggested to contribute to chromosomal instability (CIN) and aneuploidy in colorectal cancer (CRC). Previous work has also shown that the degree of DNA ploidy [DNA index (DI)], as obtained by flow cytometry in CRC, is non-randomly distributed and, in particular, that DI near-diploid and near-triploid values are well separated by a low-probability valley region. At present, it is not known whether a relationship exists between DI and the mutational status of KRAS2 and TP53. Multiple samples obtained from 35 human sporadic CRCs have been used to provide nuclei suspensions for flow cytometric analysis and sorting of specific DI subpopulations. Sorted nuclei were then used to analyze the high-microsatellite-instability (MSI-H) phenotype and the mutation spectrum of the KRAS2 and TP53 genes. A single MSI-H case was detected. There were 6 DNA diploid (DI = 1) and 29 aneuploid (DI not equal 1) CRCs, with the DI aneuploid cases non-randomly subdivided in 9 near-diploid (DI not equal 1 and DI /= 1.6) cases. Proximal CRCs were more often DNA diploid and near-diploid than distal ones, and Dukes' C cases were more commonly high-aneuploid than Dukes' B. Moreover, the incidence of mutations of the KRAS2 and TP53 genes was lowest among the DNA near-triploid subpopulations and highest among the near-diploid ones. We suggest that DNA near-diploid and near-triploid subpopulations in human sporadic CRC reflect different genetic mechanisms of CIN and have a potentially different clinical behavior.     

Use of handheld computers for assessment of prefrontal cortex function in patients with phenylketonuria

Assessment of prefrontal brain cortex function can be helpful in treatment monitoring in patients with phenylketonuria. We aimed to assess the usefulness of computerized neuropsychological tests developed for handheld computers for this purpose. We observed worse test performance among persons with blood phenylalanine concentrations exceeding the recommended range. Use of handheld computers was assessed by patients and by doctors as interesting, not time-consuming and convenient. This method can be helpful during routine follow-up visits.     

Free the Data: One Laboratory's Approach to Knowledge‐Based Genomic Variant Classification and Preparation for EMR Integration of Genomic Data

Current technology allows clinical laboratories to rapidly translate research discoveries from small patient cohorts into clinical genetic tests; therefore, a potentially large proportion of sequence variants identified in individuals with clinical features of a genetic disorder remain unpublished. Without a mechanism for clinical laboratories to share data, interpretation of sequence variants may be inconsistent. We describe here the two components of Emory Genetics Laboratory's (EGL) in‐house developed data management system. The first is a highly curated variant database with a data structure designed to facilitate sharing of information about variants identified at EGL with curated databases. This system also tracks changes in variant classifications, creating a record of previous cases in need of updated reports when a classification is changed. The second component, EmVClass, is a Web‐based interface that allows any user to view the inventory of variants classified at EGL. These software tools provide a solution to two pressing issues faced by clinical genetics laboratories: how to manage a large variant inventory with evolving variant classifications that need to be communicated to healthcare providers and how to make that inventory of variants freely available to the community.     

Correlation of AIB1 overexpression with advanced clinical stage of human colorectal carcinoma

AIB1, a member of the steroid receptor coactivator 1 family, has been cloned on 20q12 and is a candidate oncogene in human breast cancer. It is commonly amplified and overexpressed in several types of human cancers. In this study, we examined the expression of AIB1, as related to clinicopathologic features, in 85 human colorectal cancers (CRCs). The status of the number of AIB1 copies, p53 expression, and DNA ploidy was also analyzed. The overexpression of AIB1 was detected in 35% of CRCs. Amplification of AIB1 was observed in 10% of CRCs. In addition, the overexpression of AIB1 was observed more frequently in CRCs in later clinical stages (T3 N1 M0/T3 N0 2M1), compared with that in T3 N0 M0 stage (P < .05). These results suggest that overexpression of AIB1 might provide a selective advantage for the developmental growth and/or progression of subsets of CRCs. In addition, a significant correlation (P < .05) of overexpression of AIB1 with p53 overexpression as well as with aneuploid DNA content was observed in these CRCs. The overexpression of p53 was also correlated significantly with CRC DNA ploidy (P < .05). Furthermore, there was a substantial population of CRCs showing overexpression of both AIB1 and p53 protein and all had aneuploid DNA content; most of these were in the later clinical stage. These findings suggest a possible convergence of AIB1 with a pathway involving p53, which might induce chromosomal instability and affect the clinical phenotype of a subset of CRCs.     

Evaluation and costs of different haemoglobin methods for use in district hospitals in Malawi

AIMS: To evaluate the characteristics of manual haemoglobin methods in use in Malawi and provide evidence for the Ministry of Health in Malawi to enable them to choose a suitable method for district hospitals. METHODS: Criteria on accuracy, clinical usefulness, user friendliness, speed, training time, and economic costs were determined by local health professionals and used to compare six different manual haemoglobin methods. These were introduced sequentially into use in a district hospital in Malawi alongside the reference method. RESULTS: HemoCue was the optimal method based on most of the outcome measures but was also the most expensive (0.75 US dollars/test). DHT meter and Jenway colorimeter were the second choice because they were cheaper (0.20-0.35 US dollars/test), but they were not as accurate or user friendly as HemoCue. CONCLUSIONS: The process for choosing appropriate laboratory methods is complex and very little guidance is available for health managers in poorer countries. This paper describes the development and testing of a practical model for gathering evidence about test efficiency that could be adapted for use in other resource poor settings.     

Report on a training course for clinical research coordinators

Recently, nurses and pharmacists have become to play important roles in clinical trials as clinical research coordinators (CRC). However, clinical laboratory personnel have a very few chances to contribute to such tasks. CRCs have responsibility to protect the human rights, to assure the safety of volunteers during studies, and to keep quality of data. One of the authors had a chance to participate in a training course for CRC that was held in Tokyo, 2004. In this paper, we report about the training course and roles of CRC. We also discuss how laboratory personnel should contribute to clinical trials.