Developmental grants are funded through the Developmental Core of the HNRC.

The primary goal of the Developmental Grants Program (DGP) will be the initiation of innovative studies by junior faculty and trainees at UCSD or affiliated institutions with the following objectives:

1. Recruitment to neuroAIDS research of new investigators or established investigators without prior experience in the field;
2. Generation and pilot testing of new research initiatives;
3. Fostering collaboration among investigators from throughout Southern California.

The program provides to qualified investigators and trainees any appropriate combination of the following forms of support:

1. Small, 1-2 year grants to support pilot studies;
2. Access to HNRC core resources such as data, specimens, participants, equipment, administrative support, or expert consultation and technical assistance.

The application and evaluation processes for grants is semiannual, rapid, and relatively simple. For faculty, assistance will be directed to projects that can generate pilot data that support peer-reviewed proposals to outside agencies. For postdoctoral fellows, graduate students, or other trainees, the objective may be completion of projects that fulfill requirements for advanced degrees and/or result in peer-reviewed publications.

Southern California and specifically San Diego hosts a remarkable concentration of talented investigators in the biomedical and neurobehavioral sciences relevant to neuroAIDS. Fostering collaboration among these investigators by providing funding for pilot studies and support for trainees is an important secondary objective of the core.

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Scientific, intellectual, and coordinating resources provided by the HNRP

The HNRP accomplishes its objectives through the collaborative efforts of investigators and staff from multiple departments at UC San Diego who are expert in various scientific and operational aspects of research. Core areas of scientific expertise include neuropsychology, psychiatry, infectious disease, neurology, pharmacology and statistics. HNRP has developed collaborations across other disciplines that are brought in as needed for the aims of individual studies including imaging, virology, pathology, microbiome, and genetics. The HNRP team has over 30 years of experience facilitating scientific objectives through key resources and infrastructure, including data and information management, research participant accrual and retention, biological specimen repositories/banking, training and quality assurance, study coordination, statistical support and administrative coordination. These resources exist across programs and are described individually below.

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Data Management and Information Systems Resources

The Data Management and Information Systems (DMIS) Unit provides HNRP investigators and staff with a state-of-the-art web-based data management and reporting systems, and both the hardware and software for collaborative research and communication.

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Participant Accrual and Retention Resources

The Participant Accrual and Retention (PAR) Resource Group provides consultation and technical support to Investigators who are seeking relevant, hard-to-reach and/or well-characterized research subjects.  The resource group assists Investigators in rapidly and efficiently initiating studies and in successfully meeting subject recruitment goals. The group provides consultation and study design to enhance efficient resource utilization. Through technical support, the group works to ensure the overall quality of the participant’s research experience and provides Investigators with a mechanism to provide feedback regarding study findings to participants and to the local communities.  Finally, the resource group works with Investigators to monitor human subjects regulatory requirements and ensure compliance.

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Neuromedical Resources

The Neuromedical Resource Group (NMRG) serves as a resource to HNRP’s associated studies and collaborating investigators.  It provides comprehensive clinical and laboratory evaluations as well as scientific consultation, training, and community education in NeuroHIV. The HNRP’s collaborating investigators find data coordinated through the NMRG (e.g. antiretroviral (ARV) treatment information, HIV disease staging information) to be essential for their data analyses and publications.  By assisting investigators in widely diverging disciplines at all levels of project development, the NMRG encourages the application of multiple scientific perspectives and stimulates interdisciplinary collaboration, coordination and dissemination of results.

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Neurobehavioral Resources

The Neurobehavioral Group provides all HNRP-affiliated studies detailed characterizations of each cohorts’ neuropsychological, psychiatric and everyday functioning status by administering a comprehensive battery of well-validated, standardized measures of neurocognitive functioning, psychiatric, mood and substance use disorders as well as assessments of everyday functioning (e.g., successfully managing medication regimens and finances).  The Neurobehavioral Group provides demographically adjusted individual, cognitive domain specific and global summary scores for all HNRP investigators. Current and lifetime histories of substance use and mood diagnoses are provided as well.  The Neurobehavioral Group also offers training, consultation, certification and career mentoring opportunities to a host of investigators and trainees associated with local, national and international NeuroHIV studies.  Of note, the Neurobehavioral Group continues to focus its efforts on innovative studies examining the presumed interaction between aging and HIV infection, cognitive abnormalities in early and acute HIV infection, and the effects of antiretroviral treatment on HIV-Associated Neurocognitive Disorders (HAND). Ultimately, the Neurobehavioral Group illuminates the public health relevance of the HNRP both by making available critical information on the neurocognitive, psychiatric, substance use and everyday functioning characteristics of those living with HIV, and by training and mentoring the next generation of NeuroHIV investigators in the analysis and interpretation of neurobehavioral data.

Neuroimaging Resources

The Neuroimaging Resource Group provides consultation and technical guidance to individuals interested in developing pilot studies, working towards new initiatives, and modifying and managing existing neuroimaging studies. Domain expertise spans sMRI, MRS, CSI, DTI, SWI, ASL, fMRI, and PET imaging through Core personnel and the Neuroimaging Interest Group, which includes numerous highly integrated communities. For high-risk individual cases, the NI Core provides morphometric, CSI, DTI, and SWI, and, on a subset, PET PIB imaging. These volumes and derived data are available for cross-core studies; for interested individuals to further pilot hypotheses; and for multi-modal data integration, methods development and validation.

Neurovirology Resources

Neurovirology Resources are coordinated by the HIV Neurobehavioral Research Center.

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Neurobiology Resources

Neurobiology Resources are coordinated by the HIV Neurobehavioral Research Center.

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Non-Human Animal Models Resources

Non-Human Animal Models Resources are coordinated by the Translational Methamphetamine Research Center.

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Statistics Resources

The Statistics Resource Group (SRG) provides statistical assistance to researchers, trainees, faculty, and staff participating in HNRP-related research. Members of the group collaborate with investigators on study projects at all stages of the research process, including hypothesis-generation, grant-writing, sample size justifications, and development of data analysis plans. Statisticians not only analyze data with known methods but also develop, program, and implement novel statistical procedures. The Statistics Group continues involvement in a study throughout the publication and presentation of findings and is dedicated to collaborative partnerships with and education of involved investigators, trainees, and staff.

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Physical Resources

The HNRP is located on the UCSD Medical Center – Hillcrest Campus in multiple adjacent facilities. The primary location is 220 Dickinson Street, San Diego, California 92103, where the HNCRP-CMCR shares space in a 36,000 square foot 3-story building with the UCSD Antiviral Research Center (AVRC) and where the majority of HNRP research evaluations take place.

The HNRP occupies approximately 18,000 square feet of space in this building. Approximately 20% of this space is utilized for direct study participant contact and includes a reception area, staff offices, six neurobehavioral examination rooms, five neuromedical examination rooms, a blood draw room, screening room, and specimen processing laboratory. The facility also has a number of specialized rooms, including 2 negative pressure rooms supporting studies of inhaled cannabis, and a dedicated driving simulator room for examining the real-world impact of cannabis and various neurologic conditions. The HNRP’s participant facing facilities were designed to be welcoming for all members of the community and comfortable;  Our study assessments are lengthy (often a full day), and complex requiring that our space be designed to allow participants to move comfortably from room to room with ample privacy for completing questionnaires collecting highly sensitive and personal information. Study participants have access to free parking located close to the building and the building is easily navigable.

This building has three conference rooms with state-of-the-art audio-visual and videoconferencing capabilities. In addition, there is a server room, secure file room, and common area with photocopier, fax machine, and staff mailboxes. The HNRP facility supports most research activities, and also provides a modest amount of flexible space for trainees, junior scientists, and space to conduct pilot studies using human subjects.

Dedicated laboratory space and the biospecimen repository are located within close proximity. The HNRP laboratory space is comprised of approximately 2,070 square foot of web lab space dedicated to several functions.  This includes approximately 250 square feet dedicated to tissue sample preparation, in support of the aims of California NeuroHIV Tissue Network (CNTN) and National NeuroHIV Tissue Networks (NNTC), which are to serve as a national resource for access to tissues from individuals with HIV who are deceased and had detailed ante-mortem and post-mortem characterization. There is a 420 square foot laboratory used for specimen processing. Another 840 square feet are dedicated to specialized research biomarker assays.  In addition, there is a 110 square foot cold room and 450 square feet for laboratory staff offices.  The biospecimen repository is approximately 2,00 square feet. This facility has room to accommodate up to 50 freezers and is shared with the AVRC . The biospecimen repository has a dedicated HVAC system that creates a cool ambient temperature and reduces the load on the individual freezers, a monitoring system that monitors the temperature of each freezer and a back-up generator that keeps the facility powered in the event of an outage. This is a highly secured space with key card access limited to select staff members.

Please note that some of our resources are housed outside of the central HNRP facility. These include the Neuroimaging Resources, the Neurobiology Resources, and Neurovirology Resources. These resource groups require specialized laboratory facilities and are co-located with existing complementary laboratories at the UCSD School of Medicine, La Jolla campus as well as the UCSD Clinical Teaching Facility, UCSD Medical Center - Hillcrest Campus.

Neuromedical Resource Group Overview

The Neuromedical Resource Group (NMRG) serves as a resource to HNRP’s associated studies and collaborating investigators.  It provides comprehensive clinical and laboratory evaluations as well as scientific consultation, training, and community education in NeuroAIDS. The HNRP’s collaborating investigators find data coordinated through the NMRG (e.g. antiretroviral (ARV) treatment information, HIV disease staging information) to be essential for their data analyses and publications.  By assisting investigators in widely diverging disciplines at all levels of project development, the NMRG encourages the application of multiple scientific perspectives and stimulates interdisciplinary collaboration, coordination and dissemination of results.

Organization

The NMRG is comprised of two interacting subunits. The Clinical Research Support Unit (CRSU) utilizes a new model in which evaluations are performed by a team of staff research associates, nurses, nurse practitioners and physicians. Depending upon the needs of the specific project, the CRSU implements methods for structured neuromedical history-taking, neurological and medical assessment and diagnostic algorithms that facilitate establishing diagnoses of central and peripheral complications of HIV, with special emphasis on neurocognitive diagnoses. The Laboratory, Pharmacology, and Biomarker Unit (LPBU) collects, processes, stores, and makes available for future research, samples of plasma, PBMCs, CSF, and for some studies other fluids and tissues such as urine, CSF cell pellets, and buccal swabs. The LPBU also provides the HNRP with the capacity to measure ARV medication concentrations, immune mediators, and other biomarkers in CSF and plasma, and can facilitate genetics and genomic studies. Together these units perform evaluations on HIV+ subjects and HIV- controls.

Leadership functions of the NMRG are vested in a multidisciplinary team of investigators and staff: Dr. Ronald Ellis (NMRG Director), a neurologist with subspecialty expertise in neurobehavior and HIV/AIDS; and Dr. Scott Letendre (Co-Director), an infectious disease specialist with expertise in neuroAIDS and Hepatitis C infection. Management of the NMRG is provided by Terry Alexander, a clinical research nurse with over ten years of experience in applying neuromedical research methods in local and international settings.

Resources provided

The NMRG coordinates the collection of essential clinical data on human study participants, including neuromedical histories, clinical examinations, and laboratory data. A strength of the NMRG is the standardization and depth of the clinical characterization it provides. The Core Assessment is administered to most studies utilizing neuromedical resources and is designed to keep pace with new knowledge and the evolving objectives of current and future HNRP-associated studies. Core assessments offered include neuromedical history, lumbar puncture, urine toxicology, CD4 count and viral load. In addition to the Core Assessment, neuromedical data is collected as needed to meet the aims of specific studies, i.e.,stroke risk calculator, research biomakers in blood and cerebral spinal fluid

Scientific Consultation

A multidisciplinary group comprised of a neurologist, a neuropsychologist, an internist, a nurse-clinician and a psychiatrist meet regularly to assign neurocognitive diagnostic classifications to research participants. Neuropsychological test data and findings from the neuromedical evaluation (Diagnostic Worksheets) are combined to assign the following diagnoses utilizing research diagnostic guidelines: (1) neurocognitively normal, or (2) asymptomatic neuropsychological impairment (NPI), or (3) mild neurocognitive disorder (MND), or (4) HIV associated dementia.

Trainees

The NMRG offers two types of training: 1) preparation of students in a career focused on neuroAIDS 2) instruction of standardized assessments for clinical and laboratory staff assisting with local, multi-center and international studies.

Training is provided to, pre- and post-doctoral trainees, and fellows who will have the opportunity to gain experience in neuromedical, clinical assessments and pharmacology laboratory methods. Drs. Scott Letendre and Ronald Ellis serve as mentors to trainees.

Cross-project issues

The NMRG holds a weekly meeting to discuss progress of ongoing and upcoming projects. This meeting is attended by Drs. Ronald Ellis and Scott Letendre, NMRG manager Terry Alexander, physicians, nurse practitioners, research associates, and laboratory personnel. Attendees are also involved in an interactive inservice presentation to discuss HIV neurologic disorders, participant case presentations, and preliminary study results. Additionally, clinicians and SRAs have regularly scheduled meetings to address specific issues relevant to the success of daily activities within the NMRG.

Neuromedical Resource Group: Technical Details

General approaches/methods

Although it depends upon the specific needs of the study, the core evaluation includes a neurological and general physical examination performed by a clinician (physician, nurse practitioner, nurse) to detect clinical abnormalities at baseline and subsequent visits (if applicable). This examination includes an evaluation of mental status, cranial nerves, motor, sensory, cerebellar function, reflexes and gait. Other evaluations such as gynecological health history questionnaire, anthropomorphic measurements, Unified Parkinson’s Disease Rating Scale, Unified Huntington’s Disease Rating Scale, neuropathy score are performed according to specific study protocols. Training is available through a variety of modalities such as manuals, videotapes, web-based tutorials, seminars, and workshops.

Methods Training

The NMRG provides structured training for physical and neurological exams, lumbar punctures, CRF completion, participant interviews, and study protocol. Training is also provided for processing lab specimens and assays.

Quality Assurance

A weekly Continuing Education In-service program is vital to quality assurance to provide the NMRG with up to date knowledge in areas relevant to research supported by the HNRP. Data is monitored regularly to ensure that data is consistently processed and made available in the database as studies are accrued. CRFs are reviewed for accuracy, logic, and completion prior to submission to data management. Ongoing QA is also focused on certification of laboratory instrumentation, reagents, and analytic test procedures; as well as assessing precision and accuracy of final results.

Participant Accrual and Retention (PAR) Resource Group Overview

The Participant Accrual and Retention (PAR) Resource Group provides consultation and technical support to Investigators who are seeking relevant, hard-to-reach and/or well-characterized research subjects.  The resource group assists Investigators in rapidly and efficiently initiating studies and in successfully meeting subject recruitment goals. The group provides consultation and study design to enhance efficient resource utilization. Through technical support, the group works to ensure the overall quality of the participant’s research experience and provides Investigators with a mechanism to provide feedback regarding study findings to participants and to the local communities.  Finally, the resource group works with Investigators to monitor human subjects regulatory requirements and ensure compliance.

Organization

The PAR Resource Group is managed by a senior Investigator (J.H. Atkinson, M.D.) and a Manager (Roberto Gallardo). Dr. Atkinson is a Professor of Psychiatry and provides overall direction and supervision of the resource team.   Mr. Gallardo directly oversees all activities related to human subject accrual and retention, visit scheduling, and human subject regulatory compliance. Personnel include Recruiters, Schedulers, and Intake Visit Monitors. Staff members are dedicated to the specific studies and projects that support their efforts, however the group derives efficiencies and synergistic benefit from being collocated and co-managed.

Resources provided

The PAR Resource Group provides new and existing Investigators with consultation and technical support. Initial consultation may address study design and feasibility. Once a study is funded, technical support is available for identifying, screening, and enrolling specific hard-to-reach target groups. The resource includes a repository of prospectively gathered demographic and contact information on current and potential future research subjects.  The group provides Investigators with assistance in assuring human subjects regulatory compliance and provides a mechanism for Investigators to acquire feedback from participants (for example, through focus groups) and community members (via a Community Advisory Board) for the purpose of quality assurance. Upon conclusion of a study, the group can facilitate dissemination of study findings to participants and members of the local community.

Scientific Consultation

The PAR Resource Group provide consultation on recruitment methodology including state-of-the art field techniques and methods for developing and maintaining mutually supportive referral networks with health care providers, community service agencies, and local opinion leaders. The group provides Investigators with information on how to meet the challenges inherent in identifying, enrolling, and retaining scientifically relevant and diverse groups of participants. Consultation may include assistance in creating study specific educational and promotional materials.

Trainees

Training is available in study promotion and outreach methodologies, subject identification, subject screening, visit scheduling, and mitigation of barriers to participation.

Cross-project Issues

The PAR Resource Group coordinates a regular participant clearinghouse conference, attended by staff of the PAR group and each of the HNRC-associated research cores. In the course of the conference, PAR staff provide updates to team members regarding new recruitment targets, progress towards achieving existing goals, opportunities and challenges in the community, etc. In addition, staff members are trained to evaluate potential eligibility of all active studies and make appropriate internal referrals. If an individual is eligible for another study, the staff member who performed initial screening may re-contact that individual to determine whether he/she willing to receiving information on another project. A potential participant will only be referred to another study when authorization has been obtained.

Contact the PAR Resource Group

For more information about the consultation and technical support the PAR Group can provide or to access PAR resources, please contact the PAR Manager, Roberto Gallardo (This email address is being protected from spambots. You need JavaScript enabled to view it.).

PAR Resource Group Technical Details

General Approaches/Methods

Over the past 20 years, the PAR group has been dedicated to enrolling and retaining informative cohorts which, by reflecting the evolving epidemiology, comorbidities, and treatment of HIV, serves as a resource to enable investigators to efficiently address critical questions in the field of neuroHIV. Such responsiveness and relevance is the product of interactive communication between investigators, recruitment leadership and staff, and the HIV community. PAR personnel conduct community education and study promotion using social marketing and outreach in a wide range of community venues. PAR also strives to develop a genuine partnership with the HIV communities. In line with modern models of participatory research, PAR works to maintain open, consistent, and deliberate communication among all stakeholders. These types of activities are key to enrolling participants, establishing a pool of potential participants, and keeping the community engaged in the research.

The PAR group utilizes a long-range strategy of encouraging research-naïve individuals to contemplate future participation in scientific studies. This serves to enrich the pool of potential participants. The mainstays of maintenance in the cohort continue to be the principles outlined by Robins, Boice, and Showstack and co-authors, appropriately revised for HIV and cultural sensitivity, and updated for difficult-to-track samples by Anglin and colleagues. These principles emphasize education and motivation for retention at the time of enrollment and at each follow up point, identifying personal contacts, and obtaining permission to use public records to help track whereabouts (e.g., directories, locator agencies), and personalized on-going contact. The PAR group employs a full range of recruitment methods, maintaining an interactive presence in the community rather than relying heavily on mass media advertising campaigns. We distribute flyers, brochures, and posters relating to HNRP-associated study opportunities.

PAR group staff also participate in networking meetings with community members, peer advocates and opinion leaders, meet regularly with representatives of HIV care clinics and service providers, promote research at major community events, and organize and facilitate educational meetings for members of the community to provide information about HNRP research activities and solicit community input, advice, and feedback annually. Enrolled participants are asked to authorize contact by mail. If authorized, we provide information via newsletters, cards, invitations, announcements, amounting to at least four contacts by mail annually. Outreach staff are members of the targeted communities (e.g., the Recruiter/Tracker team includes men and women; homosexuals and heterosexuals; African Americans, Caucasians, and Hispanics; people in substance recovery; and people living with HIV).

Quality Assurance

The PAR Resource Group will track the involvement of longitudinal participants in various HNRP associated studies to monitor burden associated with time and effort in order to minimize the potential for participant burn-out, as well as to ensure that participants are not co-enrolled in studies that may be a cross-purposes (e.g., a clinical trial for treatment of neurocognitive disorder and a different study in which neuropsychological functioning is an outcome).

Laboratory, Pharmacology & Biomarkers Resource (LPBR) Overview

The LPBR oversees the laboratory components of HNRP-associated projects.  Depending on the needs of each individual project, the LPBR collects, processes, stores and makes available for future research, samples of plasma, serum, CSF and CSF cell pellets, urine, and genetic material (e.g. PBMCs). The LPBR coordinates routine clinical laboratory testing of these samples and also provides the HNRP with the capacity to measure ARV medication concentrations, immune mediators, and other biomarkers in CSF and blood.  This group also facilitates genetics and genomics studies. Although this work is primarily performed on samples from human research participants, the group also performs some work using animal samples.

Organization

The LPBR is housed within the Neuromedical Resource Group (NMRG). The same leadership team directs the work of the LPBR and NMRG: Dr. Ronald Ellis (NMRG Director), a neurologist with subspecialty expertise in neurobehavior and HIV/AIDS; Dr. Scott Letendre (Co-Director), an infectious disease specialist with expertise in neuroAIDS and Hepatitis C infection; Terry Alexander (NMRG Manager), a clinical research nurse with over ten years of experience in applying neuromedical research methods in local and international settings.  Within this NMRG structure, Debra Rosario, MPH, directly manages LPBR activities and staff, including laboratory assistants and research associates trained in phlebotomy and handling biological specimens.

Resources provided

LPBR resources include:

1. Personnel trained in the collection and processing of participant-derived samples.
2. Laboratory data already collected from HNRP-associated projects (with consents for data sharing) and the ability to obtain new laboratory data through retrospective testing of existing specimens or collection and testing of new specimens.
3. Storage and management of more than 500,000 specimens collected from subjects with comprehensive neuromedical and neuropsychological data who have participated in HNRP-associated studies.
4. Substantial experience in measuring and interpreting biomarker and pharmacology concentrations in relationship to HIV, methamphetamine abuse and other related conditions.

Scientific Consultation and Trainees

Although scientific consultation and training activities may be laboratory specific, these activities are addressed at the larger NMRG level.

Cross-project Issues

In addition to using NMRG methods for addressing cross-project issues, the LPBR subgroup meets weekly to address all laboratory issues including standardization of assays and methodologies across projects.  A meeting focused on pharmacology issues takes place monthly.

Contact the LPBR

For additional information or to access LPBR resources, please contact LPBR manager, Debra Rosario (This email address is being protected from spambots. You need JavaScript enabled to view it.).

LPBR Technical Details

General Procedures

Processing of Participant-Derived Blood and CSF Samples. Specific processes depend upon the details of each research protocol. But in general blood and CSF are collected, processed and separated, and aliquotted for storage or transfer to multiple clinical and research laboratories. Blood, collected by phlebotomist, is sent to UCSD clinical laboratories or Lab Corp (San Diego, CA) for hematology, chemistry, T-lymphocyte subset enumeration by flow cytometry, and HIV RNA quantitation by Roche PCR ultrasensitive assay (lower limit of detection 50 copies per mL).  CSF,collected by the physicians or nurses, is sent to UCSD labs for cell count, glucose and total protein measurements, and HIV RNA quantitation.  Both blood and CSF can be assayed in-house for ultrasensitive HIV RNA quantitation by Abbott PCR ultrasensitive assay (lower limit of detection 40 copies per mL), rapid screenings of HIV and HCV (Medmira, Nova Scotia, Canada), syphilis (RPR), urine toxicology, and specialty assays such as measurements of drug and biomarker concentrations.  Urine specimens are screened for neuroactive drugs at the time of cognitive testing by a 10-panel drug screen card (Rapid Response, Biotechnostix Inc., Markham, Canada) that immediately detects exposures to recreational or prescription drugs.

Labeling and Tracking.  The LPBR carefully tracks all processed specimens. Barcode labels identify precise freezer locations (freezer number, rack number, box number). These codes are tracked by a web-based data entry program, which was designed and developed by the HNRP’s Data Management and Information Systems Resource.  Entry of sample data by barcode also facilitates automatic and immediate update of the fluids database; accounting of sample use when a sample is processed or retrieved; and prioritization and appropriate utilization of samples. Disposition of stored fluid samples is readily defined by this tracking system. When aliquots are required for research assays or shipment to collaborators, samples are logged out and the recipient recorded. If a previously removed sample is returned after partial use, it is assigned a new location and its history noted in the database. Thus, this system enables tracking of the history of individual samples.

Specimen Storage.  The HNRP Specimen Storage Facility is comprised of -20°C, -70°C, and -150°C freezers that house all HNRP-associated biological specimens. These freezers are monitored 24 hours a day via a computerized validated environmental monitoring system that is capable of automatically phoning key personnel in the event of a power failure or freezer mechanical failure. All freezers have a posting on them listing personnel to call in the event of an emergency. The Standard Operating Procedures outline steps to take in the event of a power failure and/or freezer mechanical failure. All staff and Principal Investigators have been trained to respond to the freezer alarm system and have been given instruction of how to proceed if there is a situation requiring immediate action. Coverage is always designated to account for vacations and holiday schedules.

Participant identification, specimen procurement, labeling and confidentiality. Laboratory or clinical personnel verify the subject’s name, study identifier, visit, and date prior to procuring fluids. Local site personnel clearly label the remaining specimens with this unique identifying information prior to freezing.

LPBR personnel performance.  Copies of LPBR personnel training records are maintained. Laboratory personnel record processing times for the fluids obtained from each subject on clinical report forms and monitor these forms periodically to ensure that processing times are within 2 hours from procurement to either shipment or freezing. Efforts are made to avoid unnecessary thawing of specimens and prolonged periods at room temperature since they may adversely affect the integrity of the constituents of biologic samples.

Laboratory instrumentation, reagents, and analytic test procedures. Each clinical lab utilized by the LPBR, whether local or central, is accredited by the College of American Pathologists and or Clinical Laboratory Improvement Amendments. The designated, commercial lab is responsible for maintaining its instrumentation, reagents, and test procedures. UCSD’s Environmental Health and Safety Office monitors intramural research reagents and test procedures. Each lab verifies that they are maintaining calibration and accuracy of their instrumentation.

Turnaround times. Clinical lab results are delivered by the central, commercial lab in electronic format to the LPBR, facilitating easy monitoring of turnaround time.

Accuracy of final results. When aberrant lab results are found, their occurrence is tracked. LPBR personnel also track when such results require repeat processing. Errors are reviewed annually to identify problems with specific assays or procedures and performance of the central, commercial lab.

Complete documentation of all procedures involved in obtaining final analytic results. Documentation is maintained and monitored in a systematic manner by the central lab in the process of QA, it is important to document the effectiveness of quality control measures. The written record of quality control activities for each procedure or function should also include details of deviation from the usual results, problems, or failures in functioning or in the analytic procedure, as well as any corrective action taken in response to these problems.

Additional measures to support quality of processing and uniformity results will include:

• When thawing is necessary for processing, residual volumes that are returned to storage are marked as previously thawed and a notation will be recorded in the database.
• The accuracy of the specimen database is continually tested as groups of samples are withdrawn for specific assays. Inconsistencies (i.e., failure to find a sample in its stated location) are reported and the database promptly corrected.
• Developmental and Pilot Studies. The NMRG maintains a record of pilot studies supported, funded grants utilizing, and publications emerging from provided samples

Laboratory Operations Manual

The LPBR has developed a Laboratory Operations Manual as a resource for Laboratory Assistants and Clinical Research Assistants that includes general policies and guidelines pertaining to personnel, standard operating procedures and QA.  Specifically, the Operations Manual highlights key elements of the Biomarkers Laboratory with regard to Assay Protocols, Data Collection and Analysis, Business and Administration and an extensive QA Program that includes validation, certification and evaluation of procedures, equipment and personnel.

Biomarker Quality Assurance (QA)

The Biomarker QA program incorporates several elements, including verification of specimen labeling; tracking of laboratory personnel performance; certification of laboratory instrumentation, reagents, and analytic test procedures; assessing precision and accuracy of final results; entry of final results into the central database; and complete documentation of all procedures involved in obtaining final analytic results. To assess precision of our methods, we assay specimens in duplicate, repeating measurements that have coefficients of variation greater than 20% (~5% of assays), and repeating 10% of all biomarker assays to assess operator and batch consistency.