1_-SOW.pdf

Statement of Work

Data Analysis, Review and Entry into the PIDTC System

POP 2/15/17 to 2/14/18;

Option year one 2/15/18 to 2/14/19; Option year two 2/15/19 to 2/14/20

1) BACKGROUND INFORMATION

The research program of the Genetic Immunotherapy Section (GIS) in the Laboratory of Host Defenses (LHD), NIAID includes clinical protocols that assess natural history of primary immune deficiencies or the use of allogeneic transplant or gene therapy to treat these disorders. The GIS clinical program is particularly focused on primary immune deficiencies that include the chronic granulomatous diseases, severe combined immune deficiencies and the Wiskott-Aldrich/X-linked thrombocytopenia group. GIS has a major role in development and implementation of allogeneic bone marrow transplants and autologous hematopoietic stem cell gene therapy clinical trials in the NIH. GIS/LHD/NIAID is one of the 38 North American transplantation member centers comprising the Primary Immune Deficiency Treatment Consortium (PIDTC). The mission of the PIDTC is to evaluate the clinical efficacy and outcomes of hematopoietic stem cell transplant or gene therapy for primary immune deficiencies as compared to non-transplant standard of care. Clinical protocols have been developed by the PIDTC to study Severe Combined Immune Deficiencies, Chronic Granulomatous Disease and Wiskott-Aldrich syndrome. The PIDTC protocols are not treatment protocols, but instead are medical data collation protocols involving no patient intervention or treatment that derive and summarize data from the clinical records and clinical assessments generated from transplant or gene therapy treatment protocols or natural history/standard of care protocols. Three of the PIDTC protocols have been IRB approved for conduct at the NIH and a contract service is required to assist in the medical chart review, extraction and summary of the data and entry of this extracted/summarized data into the established central PIDTC electronic database in order to achieve compliance with the requirements of the three PIDTC protocols open for conduct by GIS at the NIH Clinical Center. These PIDTC protocols are:

Precis for PIDTC 6901 (NIH Protocol number 14-I-0072) This study is a prospective evaluation of children with Severe Combined Immunodeficiency (SCID) who are treated under a variety of protocols used by participating institutions. In order to determine the patient, recipient and transplant-related variables that are most important in determining outcome, we will uniformly collect pre-, post- and peri-transplant (or other treatment) data on all children entered into this study. Children will be divided into three strata: A) classic SCID with virtual absence of autologous T cells and poor T cell function, B) leaky SCID, Omenn syndrome and reticular dysgenesis with limited T cell diversity or number and reduced function, and C) ADA deficient SCID and XSCID patients receiving alternative therapy including PEG-ADA ERT or gene therapy. Each stratum will be analyzed separately. Outcomes for Strata B and C will utilize descriptive statistics given the small number of patients entered.

Precis for PIDTC 6902 (NIH Protocol number 14-I-0089) In this retrospective and cross-sectional study, we aim to identify variables contributing to best outcomes for Hematopoietic Cell Transplantation (HCT), Gene Therapy (GT) and Enzyme Replacement Therapy (ERT), which is life-saving therapy for children with Severe Combined Immunodeficiency (SCID), leaky SCID, Omenn syndrome and reticular dysgenesis. Because SCID and related disorders include a spectrum of immunologic presentations, and there have been several approaches to transplant, there are many questions of interest and variables to be explored.

This study is a longitudinal and cross-sectional evaluation of patients with CGD who received or are receiving hematopoietic cell transplantation (HCT) for their disease under a variety of protocols used by participating institutions compared to a control non-HCT group receiving standard care. Investigators at multiple centers caring for patients with CGD in North America and 3 centers in Europe will participate. Patients with CGD will have been treated according to institutional practice and protocols. Investigators will enroll these patients as subjects in this protocol. This study will investigate which patients benefit most from HCT, and what types of transplants are optimal for patients with CGD, in the context of overall outcomes in CGD patients with and without transplant.

2) PURPOSE AND OBJECTIVES OF PATIENT MEDICAL DATA REVIEW, EXTRACTION AND

ENTRY INTO THE PIDTC ELECTRONIC DATABASE

The PIDTC related protocols allow medical chart reviews of patients previously enrolled or about to be enrolled in ongoing natural history or hematopoietic stem cells transplant or gene therapy protocols at the NIH Clinical Center. Thus the PIDTC protocols are for the most part “derivative” of data generated from other protocols at the NIH. The contractor will be reviewing the NIH medical records of patients treated at the NIH Clinical Center. The medical records are accessed by using the Clinical Research Information System (CRIS) that is the standard electronic record repository for patients studied or treated at the NIH clinical center. The contractor will access additional patient clinical data through the NIAID CRIMSON protocol data records information system. The CRIMSON system was developed by Systex (An site IT support contractor for the NIAID since 1986), in conjunction with the NIAID, to support the documentation and data management requirements of the NIAID Intramural Clinical Research Program.

The specific task of the contractor will be to review medical records in CRIS and CRIMSON for the patients enrolled in LHD’s transplant, gene therapy and natural history protocols generating medical record information related to PIDTC protocols 6901, 6902 and 6903 where these PIDTC protocols correspond to NIH IRB approved protocols 14-I-0072, 14-I-0089, & 14-I-0091, respectively. The contractor will use the medical record review to complete the PIDTC protocol mandated record review by entering that data into those forms in the electronic entry system established and maintained by the PIDTC for this purpose. Because of patient medical data security requirements, the contractor must review the CRIS and CRIMSON records and record the information from those records using an LHD provided laptop that has the NIH required encryption software and secure systems installed for accessing CRIS and CRIMSON. The same laptop will be used to assure accurate data entry into the Primary Immune Deficiency Consortium database (PIDTC system) and for the same security reasons.

3) CONTRACTOR REQUIREMENTS:

The Contractor shall provide:

Precis for PIDTC 6903 (NIH Protocol number 14-I-0091)

a) Review of medical records, with extraction and summary of clinical data plus entry of this data into the PIDTC database for 10 to 30 patients with either Severe Combined Immune Deficiency or Chronic Granulomatous Disease who previously or are currently undergoing bone marrow transplant or gene therapy in LHD protocols. Patient clinical information required for the PIDTC protocols that already exists in the NIH Clinical Center CRIS patient data base and/or in the NIAID CRIMSON patient data base will be extracted and used to fill out the electronic data forms in the PIDTC data system.

Examples of the clinical data extracted from the CRIS and CRIMSON clinical data systems to be entered into the PIDTC protocol forms data base includes but is not limited to past medical history and current medical assessments and treatments. Two issues impact on the scope of the work. The first is that it is not possible ahead of time to be certain how much time it may take to extract and enter the data for each patient. For some patients whose transplant or gene therapy medical course was “uncomplicated”, the review and extraction of data, and entry into the PIDTC data base may take half or even a third of the time that would be the case for a patient whose medical course involved a large number of complex medical problems. Thus, we can only estimate a “range” for the total number of patient records whose review and data entry can be completed within the scope of this statement of work. It is more critical that the record extraction be complete and accurate for each patient, than that a specific number of patient records be reviewed and entered. Thus, by completion of this work order as few as 10 or as many as 30 records of patients treated with transplant or gene therapy might be completed, and still be an acceptable volume of delivery of work under this work order, which will be judged as acceptable by the completeness and accuracy of the records extracted and entered into the PIDTC database, rather than by the total number of patient records completed as long as the total number of patients completed is within the range of 15 to 35. Second, the total number of patients who fit the PIDTC protocol is expected to increase over time so that it is also not possible to know ahead of time the total number of patients whose records must be reviewed, extracted and entered into the PIDTC data base to complete the entire PIDTC project. These two unknowns; amount of time effort required to review and extract a particular patient’s records with entry into the PIDTC data base; and the final total number of patient records that need to be extracted to complete the PIDTC protocol anticipate that there may be a need to renew this contract in the future to encompass additional patient record reviews to complete the PIDTC projects.

b) Review medical records, extract and summarize clinical data and enter data into the PIDTC database for 3 to 15 patients with Chronic Granulomatous Disease followed at the NIH CC under an LHD natural history protocol who have been conventionally managed without transplant or gene therapy. This is a group of CGD patients whose medical course will be compared in the PIDTC database analysis with the CGD patient records indicated in item “a)” just above. All of the caveats regarding the need to indicate a range of records reviewed, extracted and entered in the PIDTC database under this statement of work are the same as outlined in “a)” just above apply. Accuracy of the data extraction rather than total number of patient records completed is most important. Again, as in “a)” just above, noting a range anticipates that there may be a need to renew this contract in the future to encompass additional patient record reviews to complete the PIDTC projects. With respect to the combined work performed under sections “a)” and “b)”, in the event that workload to complete reviews, data extraction and PIDTC database entry exceeds the expected timeframe, the entry of data about transplanted patients is of higher priority than the entry of data about conventionally transplanted patients. Thus, if at least 20 patients records are completed in section “a)”, then it is acceptable that zero (0) patients be completed in section “b)”.

c) The contractor will maintain communication with our Clinical group regarding data and analysis, on at least a twice a month basis as another check to assure ongoing accuracy and completeness of chart reviews, with data extraction and PIDTC database entry.

d) The contractor will provide proof of successful completion of NIH required training or maintenance of training that is required both for accessing NIH systems including access to the CRIS and CRIMSON databases and entry to the NIH campus. The contract will also remain compliance with any training required for continued access to the PIDTC database to allow entry of data into that system.

4) CONTRACTOR SUPPLIED MATERIALS

The Contractor will not be providing any materials; and will only be providing services where the final output to be delivered consists of number of accurately completed LHD patients’ medical records information entered into the PIDTC database.

5) GOVERNMENT FURNISHED MATERIALS

The LHD will provide a laptop and a printer. Contractor will use only NIH encrypted property for scanning and maintaining records.

6) REPORTING REQUIREMENTS AND DELIVERABLES

Since work is to be performed outside government facilities, a written and/or verbal report will be presented to the LHD personnel at least twice monthly to assure that the pace and direction of the work complies with expected requirements.

e) The contractor performing the service must have been previously employed in an occupation in which they have firsthand experience with Severe Combined Immunodeficiency (SCID), Hematopoietic Cell Transplantation (HCT), Gene Therapy (GT) and Enzyme Replacement Therapy (ERT), leaky SCID, Omenn Syndrome. Reticular Dysgenesis and Chronic Granulomatous Disease in order to assess diagnoses, medications, and adverse reactions to accurately compete the required PIDTC forms. Contractor must have the knowledge of the medical terms, diagnosis, etc. that relate to the aforementioned conditions to allow for expert assessment of diagnoses, medications, adverse reactions that are required to systhesize summaries of the data in the medical record.

the date of transplantation; (10) At 6-10 years past the date of transplantion or the final date of patient contact with clinical staff. Similar timetables are provided for gene therapy treatments and for conventionally managed patients. These are listed here only to provide examples of the types of patient data entry forms that would be completed in the PIDTC database by the contractor and used to assess performance and deliverables by the contractor, though the specific forms needing completion vary from patient to patient, again pointing out the difficulty in delineating the workload needed for each patient, and leading to the need to indicate a range of patient numbers whose records will be completed under this work order.

Assessment of the volume and accuracy of the service provided (PIDTC database entry of patient records by the contractor) will be performed by members of the Laboratory of Host Defense based upon reports of the data entry provided periodically to the NIH Principle Investigators from the PIDTC database managers. A written report completed monthly by the central managers of the PIDTC database noting both the number of records entered and the accuracy of record data entry, is reported to the Principal Investigators. This report provides independent assessment of how many patients records have been uploaded into the PIDTC database and assesses the completeness of the data. This will be used to assess the volume and completeness of work performed by the contractor under this work order per this statement of work. This information can only be viewed by the Principal Investigators and their surrogates including the contractor as it contains Protected Health Information (PHI) as per the HIPAA Law. In assessing the volume, completeness and accuracy of the work by the contractor, the PIs will be using the expected data entry patient event timetables encompassed by the PIDTC electronic database report forms. Examples of the specific event timetable forms to be filled out, the completeness and accuracy of which will be used to assess performance under this statement of work includes, but is not limited to the following data points for transplanted patients: (1) Prior medical history to signing on to the protocol; (2)At protocol sign ups-before and after transplant; (3) At daily records for the 1st 30 days after transplant; (4)Biweekly up to the 100 day after transplant; (4) At 6 months past the date of transplantation; (5) At the 12 months past the date of transplantation; (6)At 24 months past the date of transplantion; (7)At the 36 months past the date of transplantation; (8) At 48 months past the date of transplantion; (9) At 60 months past

INSPECTION AND ASSESSMENT OF DELIVERABLES7)