Clinical_SOW.pdf

Attachment #2

Background Statement

The NIEHS Clinical Research Program (CRP) within the Division of Intramural Research (DIR), National Institute of Environmental Health Sciences (NIEHS), has been receiving technical support for clinical research studies under contract HHSN29120055553C. This contract was awarded on September 30, 2005 and will expire September 30, 2015. The purpose of this new contract is to recompete HHSN29120055553C and continue contracted support of clinical research at the NIEHS. Many new studies and other ongoing research support services initiated under HHSN29120055553C will continue under the new contract.

Prior to HHSN29120055553C, little clinical research was conducted at the NIEHS due to the lack of infrastructure, relevant support and expertise. Initially, the CRP was small, and there were limited staff members with the relevant expertise to carry out clinical research tasks. In addition, there were no established networks and methods for identifying and recruiting research subjects, conducting specialized clinical research procedures and patient care, and managing and analyzing clinical research data. Private sector efforts existed that had access to national networks of subjects and staff with experience in many phases of clinical work that could more effectively provide clinical research support to the Division of Intramural Research. Especially for small projects, it was determined that a single team of support personnel under a central management concept would be more efficient, provide more continuity, and be more subject to quality control measures than finding and training support personnel for each project. The support services contract for conducting clinical research, HHSN29120055553C, facilitated achieving NIEHS goals which are to identify and understand genetic susceptibility and environmental influences in human disease pathogenesis, and to develop novel prevention and intervention strategies for reducing human illness and disability.

Attachment #3

Statement of Work

Introduction/Background. The Clinical Research Program (CRP) conducts or oversees clinical research studies within the Division of Intramural Research (DIR), National Institute of

Environmental Health Sciences (NIEHS). The objectives of these studies are to: 1) translate basic laboratory findings to clinical applications; 2) investigate the interaction between genetic susceptibility and environmental factors as they relate to complex traits and disease in human populations; and 3) intervene in disease development and/or progression by modifying these factors using preventative, therapeutic, and other techniques, or by altering environmental exposures, diet and lifestyles. In addition, the NIEHS conducts research on the potential health effects following natural disasters, e.g. the GuLF Study, a large prospective health study of oil spill clean-up workers and volunteers following the Deepwater Horizon Disaster. NIEHS will also collect time-critical exposure and health information to address a wide variety of research questions about the health impacts of both natural (e.g., hurricanes, floods, drought and other severe weather events) and man-made disasters (e.g., chemical spills, terrorist incidents).

The purpose of this contract is to provide medical, diagnostic, therapeutic, scientific, technical, data management, managerial, clerical, and statistical support to Principal Investigators (PIs) within the DIR, NIEHS and their collaborators. The Contractor shall assist the Government by identifying and enrolling subjects, and administering, managing, and conducting clinical studies designed and supervised by PIs alone or in collaboration with other scientists inside or outside of the NIEHS. Another purpose of this contract is to provide technical expertise and health care staff to the NIEHS Clinical Research Unit (CRU) in support of clinical studies conducted in that facility. The Contractor will also provide technical expertise and various staff members to

Clinical Research Program groups stationed at the National Institutes of Health in their Clinical

Center in Bethesda, Maryland in support of the clinical studies conducted by them. These staff will include research physicians, nurses, study coordinators, and other support personnel. The

Contractor shall function in a purely supportive role carrying out specific task orders, and shall not engage in independent research under this contract. The Contractor will also provide field research support to the NIEHS in response to natural or man-made environmental disasters, or community outreach research. Thus, the NIEHS Clinical Support Services contractor must have the contractual ability to begin work at a short notice, the logistical ability to implement NIEHS research on a national or international scale, and the expertise to perform large-scale field research as well as in-house clinical research. The Contractor should also work with NIEHS to ensure that an appropriate level of funding is maintained to allow immediate response to a disaster without contractual modifications, and also that operational plans are in place for the rapid implementation of any pre-approved research activities.

General. The Contractor shall support all types of observational clinical research studies including but not limited to genetic (genetic screening, gene x environment, genotype-phenotype association, gene modifier), cross-sectional, case report, case series, case-control, and longitudinal studies (prospective and retrospective cohort studies). The Contractor shall also support interventional studies such as: 1) efficacy trials of new treatments, new combinations of drugs, new devices, and other types of therapy; 2) prevention trials for diseases or disease progression in susceptible individuals using various therapies, diet and lifestyle changes, vitamins, minerals, and methods to minimize toxic exposures; 3) diagnostic trials aimed at developing better tests or procedures for diagnosing a particular disease or condition; 4) prevalence or screening studies to determine the number of incident or prevalent cases of a condition in certain populations; and 5) quality of life trials to explore ways to improve comfort or quality of life of individuals with a certain disease or lifestyle by modifying risk factors. The

Contractor will also support human exposure and toxicity studies and conduct or arrange for the analysis of a wide array of specimens including both biological and environment samples. In addition, the Contractor will assist the NIEHS to perform timely research of workers, volunteers, or other identified members of the community responding to a disaster situation by: 1) acquiring, organizing, and developing disaster surveys, questionnaires, other data collection instruments, research protocols and accompanying operational manuals, and implementation plans; 2) assuring IRB-approvals for the disaster and other protocols and that all related study documents are in place; and 3) maintaining and developing forms, instruments, study tools, and related content for on-line accessibility to ensure readiness to rapidly implement operations to perform research response activities as soon as possible when a disaster occurs.

Individual research projects will be identified as Task Orders which will include but not be limited to: 1) providing expertise in study design and analyses; 2) developing study protocols for internal and external reviews (scientific, IRB, OMB, HIPAA, FDA, other) and other study materials (informed consent forms, manuals of operations, questionnaires, data collection forms, phone scripts, advertisements, websites, study pamphlets, etc.); 3) identifying, evaluating, diagnosing, and recruiting study subjects; 4) developing and administering subject brochures, informed consent forms and Health Insurance Portability and Accountability Act of 1966

(HIPAA) consent forms; 5) performing or overseeing clinical evaluations, diagnostic procedures, clinical laboratory testing; 6) collecting biological samples and performing clinical, biochemical, molecular and analytical laboratory analyses of human biological samples; 7) administering and monitoring interventional treatments including drugs, vitamins, minerals, dietary supplements and other chemicals; 8) overseeing and monitoring the care of patients on an in-patient and out-patient basis; 9) monitoring adverse effects; 10) aiding in the design, development, validation, and foreign language translation of study materials and instruments such as questionnaires; 11) interviewing subjects, administering questionnaires, and abstracting records of study subjects;

12) designing data collection instruments, e.g. case history forms; 13) collecting, transporting, analyzing, storing and shipping environmental and/or biological samples such as blood, urine, and other biologic products or tissues from humans between various facilities, e.g. NIEHS, storage facilities, reference or collaborating laboratories; 14) creating and maintaining electronic study databases; 15) keying, editing, updating and recording data; 16) conducting sample size

(power) calculations and statistical analyses of study data; and 17) disseminating results by aiding in the development of tables, graphics, presentations, manuscripts, and other types of reports.

The extent of clinical research studies being conducted by the NIEHS is growing rapidly, and it is not possible to completely determine in advance either the nature or number of studies to be conducted over the period covered by this contract. The study design and implementation of research projects will be the responsibility of the DIR PI with advice possibly being sought from the NIEHS Contracting Officer Representatives (CORs), Contractor or a contracted panel of experts. The COR will initiate the study via a Task Order Request for Proposal submitted to the

Contracting Officer. The extent of the Contractor's involvement with any given study may vary depending on the study design and support available in-house or through collaborators. For example, the Contractor might carry out only the surveillance and recruitment phase of a study, or only develop and administer study questionnaires. Alternatively, the Contractor might be involved only in the treatment or sample collection phase of a study. In some cases, the

Contractor will be involved in all aspects of a study from study design to study implementation, analyses and reporting of results. The Contractor must have the flexibility to meet the specific needs of multiple DIR PIs at variable times during conduct of their clinical research projects.

Specific Responsibilities

1. Provide Contract Staff The Contractor shall provide all administrative, scientific, clinical, expert, and support staff to conduct contract activities described below. Contract staff will be stationed at Contract headquarters, NIEHS (main building and Clinical Research Unit), NIH Clinical Center

(Bethesda, MD), and at other remote sites within and outside the U.S. where clinical research studies might take place.

2. Quality Management Plans

The Contractor shall submit a Quality Management Plan for the overall contract and if requested by the COR, for individual Task Orders. The Quality Management Plan shall address the areas described below. Once a Quality Management Plan is approved by the COR, the Contractor will implement it. The Quality Management Plan shall address:

a. Mission and quality assurance policies of the organization;

b. Specific roles, authorities, and responsibilities of management and staff with respect to

Quality Assurance (QA) and Quality Control (QC) activities;

c. Means by which effective communications with personnel actually performing the work are assured;

d. Processes used to plan, implement, and assess the work performed;

e. Processes by which measures of effectiveness for QA and QC activities will be established and how frequently effectiveness will be measured;

f. Documentation of QA and QC endpoints and reporting;

g. Continual improvement based on lessons learned from previous experience.

h. In administering consent forms, surveys, and questionnaires to subjects, the Contractor shall develop criteria for good interviewing practices. The Contractor shall also develop a

QC plan to monitor interviews, provide monitoring documentation and results to CORs and investigators, and implement corrective actions.

3. Study Initiation and Liaison

The Contractor shall:

a. Obtain necessary information to determine effective study resources (e.g., capabilities of collaborating institutions, numbers of eligible study subjects, exposure information, etc.)

b. Determine the parties whose cooperation or approval is necessary for implementation of the study (e.g., federal, state or local government agencies, local institutions such as hospitals, clinics, physicians, private industry, industry associations, labor unions, extramural institutions and collaborators).

c. Arrange for communications and meetings between investigators, collaborating institutions and agents from whom cooperation or approval is necessary. Arrange for travel for such individuals.

d. Attend such meetings, provide required background material, keep minutes and take appropriate actions on recommendations.

e. For multi-center studies, develop procedures to assure that the investigation is being conducted in a standardized manner at all sites.

f. Make arrangements for translations for necessary transactions to initiate studies in local and foreign settings.

g. Negotiate and manage all financial and administrative matters related to the collection, back-up, and analysis of data, environmental samples and biologic specimens; when necessary, identify individuals or institutions capable of doing the work, and make necessary arrangements (e.g. subcontract, purchase of equipment, other compensation).

h. Develop protocols and complete forms and letters for various committees such as scientific review boards, Institutional Review Boards (IRBs), Office of Management and

Budget, Food and Drug Administration (FDA), Reliance Agreements, etc. Attend the meetings of such committees as directed by the COR.

i. Develop applications for Certificates of Confidentiality.

j. For studies requiring an ongoing advisory committee or a data and safety monitoring board, make necessary arrangements to support communication and meetings, including making travel arrangements for meetings and site visits and arranging compensation.

k. For studies requiring preliminary workshops, provide sites and support for such workshops.

l. Arrange focus groups.

m. Carry out pilot and validation studies, feasibility studies, and studies to determine ranges of exposure and size of exposed population(s).

4. Study Operations and Review

a. Conduct periodic review of study progress, data entry, data quality, and data analyses

b. Arrange Scientific Advisory Committees to review study design and study progress

c. Arrange for communications and meetings between scientific advisory members and study investigators, collaborators and collaborating institutions, and all other relevant staff to review study progress and goals.

d. Arrange for travel for such individuals.

e. Attend such meetings, provide required background material, keep minutes of such meetings and take appropriate actions on recommendations.

5. Development of Study Materials and Procedures

a. Prepare, pretest, evaluate and produce data collection forms (e.g. abstract forms, coding forms, case report forms, questionnaires, follow-up forms, tracking forms, biological specimen collection and processing forms, and exposure assessment forms).

Questionnaires may be self-administered, paper or electronic or computer-assisted. As study sizes can range over orders of magnitude, the Contractor shall tailor the expense and complexity of the proposed interview techniques to the size and complexity of the study at hand.

b. Prepare other study related materials such as study pamphlets, letters, newsletters, and other communications to subjects, study incentives (e.g. magnets, rulers, etc.)

c. Prepare study advertisements such as websites, newspaper articles, press releases, posters, banners, etc.

d. Prepare training programs and materials for abstractors, interviewers, clinicians, and other study personnel.

e. Prepare procedure manuals for medical abstractors, coders, interviewers, phlebotomists and other medical personnel involved in specimen collection, tracers, data editors, supervisors and industrial hygienists.

f. Prepare procedure manuals for the collection of biologic specimens; shipment of specimens, submission of specimens to repositories, and tracking of specimens and laboratory results.

g. Prepare procedure manuals for the collection, processing, and storage of environmental specimens (air, water, dust, soil, carpet and other indoor materials in residential, agricultural or industrial settings);

h. Prepare manuals for obtaining, handling and abstracting medical records, pathology specimens and reports, submission of pathology specimens for review, and collection of death certificates. Arrange for review of these reports, measurements, or specimens.

i. Develop or adapt existing schemes of coding for categorizing medical, family history, demographic, occupational, industrial, nutritional, geographic, medical or other information.

j. Translate data collection instruments or manuals into appropriate languages for foreign studies or for use with non-English-speaking US residents. Under the direction of the

COR or PI, back-translate either a portion of the material or all material into English to assure that the original intent of the material has not been changed by the translation.

k. Arrange for specific laboratory analyses of biologic and environmental samples. Prepare subcontracts, as necessary, to achieve these analyses. Carry out pilot studies, identify expert opinion, or use other appropriate means to identify competent laboratories.

l. Assemble individual subjects' records, which may include hospital or physician records, death certificates, pathology reports, prescription or billing information, etc. Have these records and certificates evaluated and coded by appropriate nosologists (disease classification), pathologists or clinicians.

m. For activities that are similar across studies, design or use systems and approaches that can serve as a "shell" or "template" for future work in order to avoid reinventing such systems for each study or Task Order.

6. Subject Identification, Selection, Tracing, and Recruitment

a. Develop methods for identifying, tracing, or recruiting study subjects and make recommendations on the feasibility of alternative schemes. Subjects could include individuals who have been historically difficult to recruit (e.g. minorities, children, migrants, individuals at low literacy levels, individuals with limited understanding of the

English language, and other underserved populations and groups. Typical study groups include:

i) Patients diagnosed with some condition occurring in a particular group of hospitals or clinics or residing in a given geographic area;

ii) Controls which may include patients free from subject disease, diagnosed with control diagnoses, subjects sampled at random from a given geographic area sometimes matched to cases on age, gender, race, and other characteristics; and

iii) Groups of individuals with selected occupational, dietary or other environmental exposures.

b. Develop and implement procedures to monitor recruitment rates. Recruitment rates will depend on the study. For example, recruiting patients with rare diseases may take more time than recruiting patients with common conditions or control subjects. Recruiting subjects for long term or comprehensive studies may take more time than recruiting patients for simple procedures, e.g. blood collection, simple surveys. Also, recruitment for human subjects research in the period immediately following disasters will by necessity have to be more rapid and be implemented quickly. Based on the needs of the

Investigator in regards to his/her study, the Contractor will set recruitment goals, develop procedures to monitor recruitment rates, and develop and implement backup methods to increase recruitment if the goals are not met.

c. Use methods to derive appropriate control series for use in case-control studies. This could include a variety of different types of controls, including (but not limited to) those derived from hospitals or clinics, random digit dialing, area surveys, employer personnel or labor union records or population rosters. When such methods as recruiting from various venues or random digit dialing are performed, clear documentation shall be kept so that precise response rates can be determined for all phases of the telephone screening, and reasons and demographic characteristics can be summarized of subjects who refuse to participate or who are lost to follow-up.

d. Acquire appropriate population rosters or files to identify selected series of potential study subjects. This will require familiarity with current privacy regulations, e.g. HIPAA.

e. Maintain contact with study subjects through various campaigns that might include letters, telephone calls, email, etc.

f. Follow, and if necessary, trace study subjects to locate them for interview, environmental measurements, biologic specimen collection, or clinical examination. Determine their vital status and the presence or absence of specific diseases or conditions. Collect information and specimens that will allow for assessment of exposure to specific environmental, dietary, agricultural, industrial, or other agents thought to affect disease status. Collect information and specimens that will allow laboratory assessment of genetic susceptibility by whatever state of the art methods are used in a specific study.

For deceased or incapacitated subjects, it may be necessary to locate next-of-kin or other proxy respondents.

g. For retrospectively ascertained subjects, use a variety of tracing techniques to ascertain current vital status. For living subjects, locate their current whereabouts so that they can be included in studies.

h. For prospective studies, monitor and track participants to minimize loss to follow-up and promote high response and retention rates.

7. Data Collection

a. Train abstractors, interviewers, telephone screeners, coders, phlebotomists, clinicians and others who will be involved with acquiring and assembling data.

b. Oversee field activities.

c. Abstract data from various mediums including paper and electronic records, microfilm, and other. Ensure that abstractors know terminology (e.g. medical terminology if abstracting from medical records, hospital charts, and vital records; occupational terminology if abstracting from employment records; environmental/chemical terminology, national, international, or other databases, etc.). Make sure abstractors can recognize discrepancies in records, and that they review all data before making data abstraction decisions. Maintain quality control over the abstracting or copying process.

Verify a sample of abstracts by independent re-abstracting and implement other measures for assuring quality abstraction.

d. Obtain the necessary permission for data collection.

e. Interview or otherwise collect data from subjects or surrogates using mail, telephone, computer-assisted, in-person, e-mail or web-based interviews. Use appropriate techniques to obtain acceptable response rates, including offering financial or other incentives. Tape the interviews if specified and follow all legal requirements and regulations in taping interviews. Verify a sample of completed questionnaires by re-interviewing subjects. If verification indicates a problem, develop and implement ways to correct the problem.

Evaluate the state-of-the-art for technology dependent techniques such as computer assisted telephone interviews, and arrange through licensing or subcontract (if necessary) to use the appropriate techniques.

f. Arrange for clinical diagnostic studies, laboratory evaluation of study subjects and environmental measurements.

g. Monitor quality assurance/quality control of ongoing laboratory analyses, rapidly integrate laboratory results in study databases, carry out graphical and statistical analyses, and assist with monitoring the availability of, and managing the use of, biologic samples stored in NIEHS repositories.

h. Obtain all necessary laboratory reports.

i. Procure death certificates from state vital records departments.

j. Develop and manage flexible and efficient computerized tracking systems that monitor participation rates for all aspects of a study. The tracking of recruitment and participation must provide the information required for efficient study management, e.g., allow appropriate timing of contacts, permit updating of contact information, etc. The systems must also generate participation and loss rate data for all aspects of a study, from eligibility pool through completion, and also permit immediate ascertainment of which parts of a complex study a given subject has completed.

k. Monitor and/or evaluate current and/or historic environmental exposures or determinants of exposure.

l. Validate exposure or disease histories obtained in interviews by obtaining original records. This includes maintaining a management tracking system for the retrieval of such records.

m. Develop management tracking systems that monitor the incoming flow of data, editing of data, back-ups, and changing or modification of data that can be summarized into descriptive reports.

8. Conduct Interventional Clinical Studies and Clinical Trials

a. Aid in the design, and implement and conduct different types of clinical trials including treatment, prevention, diagnostic, screening, and quality of life trials. Treatment trials might or might not be FDA-regulated and might or might not include phases (I-IV).

Treatments might include drugs, drug combinations, devices, or other medical means to intervene in the development or progression of disease. Other clinical trials might involve changes in diet, lifestyle, behaviors, or the provision of specific services to affected and/or high risk populations and controls.

b. Develop applications for Investigational New Drugs (INDs) or Investigational Device

Exemptions (IDE), and oversee their submission and review.

c. Investigate and determine applicable local, state, federal, international and other types of guidelines, laws and regulations such as Good Laboratory Practices and Good Clinical

Practices and ensure they are followed in study conduct.

d. In conducting clinical trials, follow all regulations outlined by the Office of Human

Research Protections (OHRP) and Code of Federal Regulations (Title 45 CFR 46 for clinical studies, Title 21 CFR 50 for FDA-regulated clinical trials, and Title 40 CFR 26 for EPA clinical research studies).

e. Identify and select appropriate facilities and staff required to administer intervention, and arrange all aspects of intervention. Administer treatments and/or implement intervention in study subjects. Once patients have been identified, evaluated, and enrolled into a study, the Contractor shall either administer or oversee the administration of interventional therapies and monitor endpoints for patient safety and risk reduction evaluation.

i) Therapeutic treatments can include: the administration of drugs by oral, topical, iv, subcutaneous, and intramuscular injections, shunts or other routes of entry; the administration of vitamins, supplements and other chemicals; and other types of therapy. Depending on the study, the therapeutic treatment may be administered on an in-patient or out-patient basis.

ii) Preventative therapies can include but are not limited to dietary modification, exercise programs, behavior modification and various methods to minimize exposures.

f. Devise and implement monitoring methods to ensure subject compliance, and measure study or risk reduction endpoints. The Contractor shall monitor and report on the safety of the subjects and all adverse events, and comply with other safety requirements set forth by the IRB. Data monitoring methods will be developed and agreed upon by the

COR and PI with expert advice of the Contractor.

g. On occasion, the Contractor shall conduct clinical research projects using military subjects. Therefore, they shall investigate military and Veterans Administration guidelines and regulations for these research projects, and comply with them during study conduct. This will also require that the Contractor understand military culture and how to work with military and civilian defense leaders.

h. Select members and organize Data and Safety Monitoring Boards (DSMBs) following appropriate guidelines when required. Arrange DSMB meetings which are to be held in person, teleconferencing or other means. Develop DSMB agenda and charters and moderate DSMB meetings.

9. Provide Medical Care to Study Subjects on an In-patient and/or Out-patient Basis

a. Demonstrate the ability to provide medical care to subjects who are adjunct to or are part of a clinical study. The Contractor shall demonstrate the ability to partner with local and nonlocal institutions to provide said care. The types of care will depend on the study, and must be clearly outlined by the COR or PI. Medical support may be needed for initial subject evaluation and diagnosis, interventional treatment, and follow-up care. Medical support may be given on an out-patient basis at the Clinical Research Unit on NIEHS campus, physician’s office, clinic, or at the subject’s home by a home health care technician. Other types of medical support, including surgery, chemotherapy, and physical therapy, may require hospitalization at sites such as the UNC, Duke Medical

Centers, the Clinical Center at the NIH in Bethesda or other major medical centers throughout the US and in foreign countries. The Contractor shall support all types of medical care for clinical trials by providing expert personnel, identifying a site for medical treatment, and arranging and overseeing the actual treatment and monitoring follow-up care. All study procedures supported by this contract that require medical care must be approved by the Clinical Director, COR and PIs, or others appointed to review the study protocols.

b. Identify and hire medical and other study personnel to administer or oversee treatment and preventative therapies, provide medical care, monitor subject compliance, and measure risk reduction and adverse events.

c. Provide administrative, medical and research staff to the NIEHS Clinical Research Unit and NIEHS units in the NIH Clinical Center to collect data and specimens, provide health care, and administer and monitor interventions.

10. Specimen Collection, Processing and Shipment

a. Arrange for or conduct all aspects of biologic, occupational and environmental sample collection, handling, transport, storage, analysis, and information processing. The samples may be a component of a Task Order under this contract or provided to the

Contractor from other Government contracts.

b. Train phlebotomists and others who will be involved in collecting specimens.

c. After obtaining necessary and appropriate informed consent, obtain biologic specimens

(e.g. peripheral venous blood, skin, nails, hair, urine, buccal cell mouth wash samples, saliva, etc.) from study subjects. Divide samples, package them as instructed and ship, transport or deliver them to a designated repository, laboratory or laboratories. Inventory all laboratory samples. Pertinent data concerning the specimen donor and processing procedures shall be collected and accompany every biologic specimen.

d. Collect and deliver biologic, industrial or environmental samples to laboratories or other designated sites for storage and/or analysis. Perform other support activities involving collection, storage and/or shipment to laboratories, as requested by the COR or PI.

e. Collect, inventory, process, track, store, and transport human biologic materials to laboratories using sterile techniques. Typical procedures include collection of urine specimens, transporting specimens on dry ice, collection and centrifugation of blood, division of samples into individual aliquots, and simple cell isolation and culturing techniques; processing human blood cells for long-term storage (cryopreservation or

DNA extraction), performing lymphocyte counts, receiving and storing tissues; and collection of other biologic materials including but not limited to hair, feces, semen, amniotic fluid, tissue, toenails, and pathology specimens. Specimens may be collected locally, in the continental US, or from foreign countries.

f. Ensure that adequate caution is maintained by employees working with materials that present a biological hazard, e.g., human tissues. Safety procedures as outlined in the

NIEHS Health and Safety Manual (see http://www.niehs.nih.gov/odhsb/manual/man7c.htm) and regulations detailed by the

Occupational Safety and Health Administration (OSHA Standards – 29 CFR Part 1910) shall be followed.

g. Develop and implement standard procedures adaptable to each site where work is being performed and utilize such standard approaches at all sites where possible in order to minimize variation in handling and processing of specimens.

h. Arrange for short term onsite storage and/or safe shipment of biologic specimens (on dry ice or other means as appropriate) to Government repository or one of several laboratories, for either immediate assays or storage. The Contractor shall not store samples long-term but shall work with other government contractors or investigators in archiving samples and maintaining electronic inventories at other facilities for long term storage, and in retrieving samples from long-term storage.

i. Provide and maintain state-of-the-art monitoring devices for onsite freezers and refrigerators 24 hours/day for failures, notify the COR of need for offsite storage, and ensure the removal of specimens to appropriate backup freezers when necessary.

Monitor backup systems of all freezers regularly. Notify COR or responsible PI of the potential for sample degradation, length of time thawed, etc.

j. Provide laboratory space in Contractor's facilities for Government Furnished/Owned freezers, refrigerators, and other laboratory equipment. The Contractor shall be responsible for the oversight of freezer and refrigerator units located within their facility and shall make arrangements for the security, maintenance, and repair of such equipment.

k. Report to the COR all irregularities, delays, losses, deteriorations, unplanned defrosting, accidents, mishandlings, errors, discrepancies and significant inefficiencies connected with any specimen collection, delivery or storage activity.

l. Maintain an inventory of specimens from clinical studies provided from this contract, previous contracts, other Government contract(s), or from other activities using appropriate software program. The COR or responsible PI shall be consulted about options on inventory software. Monitor inventory discrepancies with field reports, other laboratories, and Government repository laboratory.

http://www.niehs.nih.gov/odhsb/manual/man7c.htm

m. Develop management systems for tracking results as they derive from various contracting laboratories for rapidly evaluating laboratory performance on blinded quality assurance/quality control samples within and between lab batches and for rapidly communicating these results to COR or appropriate PI.

n. Obtain all laboratory reports and process and deliver them immediately to the COR.

Rapidly merge laboratory results into primary study inventories and databases and carry out initial graphical and statistical analyses as requested.

11. Conduct Study-Related Community Outreach

a. Identify and organize community groups in support of clinical research studies.

Community group members might consist of individuals from local business, community centers and groups, churches, schools, medical clinics, local government, media outlets, and other. Community groups might be organized to have input into study design and operations, act as liaisons between scientists and subjects, build trust between scientists and subjects, incorporate cultural influences into study procedures, develop strategies and aid in subject identification and recruitment, and disseminate results.

b. Set goals for community groups, communicate with them, and organize community group meetings.

c. Organize and conduct focus groups with community members for research attitudes, to inform study design, survey for opinions, and other issues.

12. Specimen Analyses

a. Depending on the requirements of individual Task Orders, conduct or arrange for the analysis of a wide array of specimens including both biological and environment samples. This will include genotyping human biological samples using high and low-throughput methods.

b. Prior to conducting analyses, the Contractor shall develop appropriate Standard

Operating Procedures outlining the materials and methods, methods used to check sample quality, e.g. electrophoresis for RNA, other samples or measures that will be used for quality control testing, and methods for recording, documenting and analyzing data.

c. As part of a Task Order for specimen analysis, the Contractor may be required to provide documentation that they have experience with a particular assay. For example, if RNA isolation is part of a Task Order, the Contractor might be required to submit photos of previous RNA gels or produce data of RNA quantities from certain tissues.

d. Conduct genotyping on human biological samples

13. Data Preparation and Processing

a. Code or enter questionnaire responses, clinical and laboratory information, etc. into computer readable form. Verify a sample of the coding by independent re-coding. The size of the sample shall be approved by the COR or PI. Summarize and describe differences between the two sets of data.

b. Develop documentation of codes used and listings of unusual responses.

c. Enter coded information onto suitable computer devices. Verify all or at least a 10% sample (at the discretion of the COR or PI) by re-entry (e.g., key punch and verification).

Summarize and describe differences between the two sets of data.

d. Ensure the quality of all data collected, and the uniform processing thereof. Routinely run file compare procedures to compare the manually-created files to shipment records and to other computer generated files. For studies involving family groups, establish and run person-checks within appropriate data to ensure correct family groupings. Review questionnaires and data gathering forms and instruments for clarity.

e. Determine the most error free and efficient system available, including state of the art handling of data from computer assisted interviews or scanned documents. Provide training for and implement such systems.

14. Computer Programming

a. Design and maintain computer databases and associated reporting software including software such as enrollment and participant tracking, computer assisted interviewing, web-based enrollment and interviewing, and other techniques needed for support of studies in the field. Provide expert advice on the most appropriate, cost effective and efficient data processing system to be used in support of specific requirements, setting up and maintaining a multi-user computer network with shared software and data backup capabilities. Provide adequate validation when new software is developed.

b. Prepare, edit programs, edit data, and correct computer files where necessary. Describe findings in summary form.

c. Update files with follow-up data, error corrections, etc. as directed by the COR or PI.

Maintain clearly documented history of development and updating of databases.

d. Prepare data sets for transfer to PI or others, as specified by the COR or PI.

e. Produce analyses specified by the PI. These may include simple descriptive statistics or complex genetic and epidemiologic analyses, including cross-tabular and graphic presentation of data, statistical analyses with parametric and nonparametric techniques

(including multivariate regression, logistic regression, categorical analysis, survivorship procedures, and Bayesian methods). Have the capability to use a broad range of computer programs (e.g. SAS, SUDAAN, S Plus, Strata) as requested by the PI for a given study.

f. Provide customized summaries of lab assay results and other complex data. Provide innovative tools for visualizing epidemiologic and laboratory data.

g. Develop and maintain internal record-keeping procedures for assessing efficiency and quality of data collection, preparation, back-up, and entry.

h. Respond rapidly to high priority, unanticipated requests with appropriate activities and use of personnel.

i. Analyze complex survey data (i.e. SUDAAN) and GIS data (e.g. Arcview) and for merging GIS or other data with health, medical, epidemiologic and other types of data.

j. Research, evaluate, procure and test hardware, including servers, backup systems, PCs, printers, network devices, etc.

k. At the completion of selected studies, prepare, document and test an archival version of the analytical dataset appropriate for public access. The current realization of such a dataset would be a CD containing data and documentation that could be shipped on request to interested investigators, but the format and the media may change over the course of the contract period.

15. Quality Assurance/Quality Control and Reporting

Quality assurance/quality control procedures consist of the following:

a. Document each step of a study and maintain all relevant material in an orderly manner, so that any aspect of the study may be reviewed and evaluated by the Government with little or no prior notice. Contractor activities related to documentation shall include the following:

i. Prepare letters, forms, and other documents necessary for the conduct of the study.

Most studies shall require a Manual of Operations unless the COR or PI determines that one is not necessary.

ii. Duplicate study documents when the original sources cannot be retained except where expressly precluded by law (e.g. death certificates which must be destroyed after a certain time limit).

iii. Maintain a filing system of all materials relevant to the study (including computer analysis programs), cross-referenced in a manner so as to make all of the material easily accessible. These materials shall be maintained under security in accordance with requirements of the Privacy Act.

iv. Maintain a log of decisions (see d below).

b. Develop procedures to identify appropriate laboratories and to monitor quality assurance/quality control as the analysis of study samples proceeds. This includes checks such as spiked, blank and duplicate samples. Develop strategies for obtaining ongoing quality assurance/quality control data and for monitoring of laboratory procedures for drift or other systematic error.

c. Develop internal record keeping procedures for assessing the progress of data collection, data preparation data entry and back-up.

d. Maintain a log of scientific decisions made during the study that affect the study design, conduct, or analysis. Examples of such decisions are amendments in criteria for matching cases to controls, and selection of job codes for ambiguous job titles. The log may consist simply of copies of relevant memos, emails, notes from telephone conversations or meetings, but must include, as a minimum a brief explanation and date of the decision and name of the PI responsible for the decision as well as overall responsibility for the

Task Order. Documentation shall include a record when a specified change was operationalized in the field. All decisions that increase the cost of a Task Order by 10% or more or affect its performance schedule shall be referred to the COR, in advance, for approval.

e. Report verification rates, discrepancy rates, and error rates for data collection, preparation and keying following the schedule agreed upon with the COR. Any unusual problems shall be brought to the immediate attention of the COR.

f. When necessary, acquire the services of an industrial hygienist certified by the American

Board of Industrial Hygiene who has access to the appropriate measuring equipment.

Samples shall be analyzed by a laboratory certified by the American Industrial Hygiene

Association. When necessary, acquire the services of medical records abstractors and/or nosologists for ICD coding of records and death certificates.

g. Upon completion of each Task Order, the Contractor shall convert all original questionnaires, updated Manual of Operations, and other relevant study materials to a form suitable for efficient long-term storage, e.g. electronic files, CD ROM, or optical disk storage. Storage materials shall be labeled with study name, Task Order number, NIEHS PI name, and date of completion. The Contractor shall also compile a compendium of study procedures, forms, and analyses. The Contractor shall prepare archival data files for transfer to a designated location at study or contract completion.

h. Provide monthly, quarterly, annual (fiscal year), and final technical progress reports and budget reports to COR and PI.

i. Create and maintain websites for long-term studies.

j. Provide data management/statistical programming support for clinical studies’ initiation, set-up, maintenance and close-out

k. The Contractor shall monitor expenditures on Task Orders, provide the COR and PI with adequate warning of expenses in excess of budget.

16. Develop General Resources to Support Clinical Research

a. Devise strategies for identifying specific tissues e.g. viable cells, tissue cultures, biopsies, cancer tissue, cadaver tissues, DNA, etc., and collect them for tissue registries..

b. Devise strategies for identifying environmental samples e.g. air, dust, soil, occupational products, etc., and collect them for sample registries and/or analyses.

c. Devise strategies for identifying patients or other individuals, e.g. individuals with specific lifestyles or exposures, and enroll them into Patient or Population Registries;

d. Develop organizational structure for maintaining and operating archives and registries;

e. Provide facilities for tissue archives and population registries;

f. Provide ethical, managerial and other types of oversight in the maintenance of various tissue archives and patients registries;

g. Develop and maintain databases for tissue archives and populations registries;

h. Develop policy and mechanisms to share samples, data, and study subjects with other scientists;

i. The Contractor shall be responsible for only short-term storage of archive samples but shall work with other government contractors and investigators to maintain samples long term in other facilities.

17. Staff Training

a. Develop and implement training programs for both Contract and non-Contract

(government employees and their collaborators) staff in activities related to this Contract.

This shall include but not be limited to training relevant staff in: 1) human research protections and ethics; 2) NIEHS CRU and NIH Clinical Center operations; 3) contacting, recruiting, and interviewing study subjects; 4) consenting techniques; 5) tracing techniques; 6) data collection and entry; 7) administering surveys and study interventions; 8) providing medical care or therapeutics to study subjects; 9) collecting, processing, inventorying, maintaining, and shipping all types of study samples; 10) performing sample analyses; and 11) conducting QA and QC procedures;

b. Develop and implement training programs for both Contract and non-Contract

(government employees and their collaborators) staff in relevant regulations and guidelines that pertain to study activities. These might include but are not limited to training staff in Good Laboratory Practices (GLPs) and Good Clinical Practices (GCPs), FDA regulations, Codes of Federal Regulations for protecting human research subjects, maintaining electronic records and US Post Office regulations for shipping hazardous or biological materials.

c. Document training of individuals, and develop and submit training reports to COR and

PIs;

d. Develop programs to retrain study staff based on QA results and other programs developed to monitor study staff activities.

18. Study Monitoring

a. Monitor studies following guidelines developed by the NIEHS Office of Human

Research Compliance.

b. Develop study monitoring methods by identifying the data/documents to be monitored;

the review experts (study monitors or clinical research associates (CRAs); the time points of data review; the safety and/or action limits if appropriate; and the corrective actions to be taken if the limits are exceeded.

c. Review data to verify and document informed consent and adherence to federal and NIH regulations and guidelines, e.g. Good Clinical Practices, HIPAA, others.

d. Provide COR and Investigators with reports of findings.

19. Security

a. Provide security for their facility and all storage areas in their facility, and for the materials, specimens and data stored therein, and for non-Contract facilities where data, documents, materials, and samples are stored;

b. Provide security for all refrigerators and freezers maintained at the Contractor’s facilities, and at other facilities where the Contractor is storing samples;

c. Ensure all freezers in the Contractor facility and at other facilities where study samples are stored are connected to a central alarm system, which is continuously monitored 24 hours per day. The system shall notify designated responsible Contractor personnel in the event of freezer malfunction;

d. Respond immediately to emergency freezer malfunctions and take appropriate action

(i.e., transfer specimens to standby freezer in the event of malfunction).