Q301--Growth Hormone Replacement Therapy Lab Testing Services

This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued. The solicitation number 36C24E22Q0062 is issued as a request for quotation (RFQ). The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 2005-92. This requirement will be made using a cascading set-aside under the associated NAICS code 541380 with a small business size standard of $16.5 Million. The full solicitation document is included as an attachment to this notice; to include: a list of contract line items, a Description of requirements for the items to be acquired, SOW, Date(s) and place(s) of delivery, and applicable clauses and provisions. Evaluation procedures: Evaluation of offers will be made in accordance with FAR 13.106-2, and award made based on the lowest price technically acceptable and in accordance with tiered SDVOSB small business set-aside procedures. Purpose Growth Hormone Replacement Therapy in Veterans with mild Traumatic Brain Injury and Adult Growth Hormone Deficiency (the GRIT Study) is a research study sponsored by the Department of Veterans Affairs (VA) Cooperative Studies Program (CSP). The purpose of this multi-center clinical trial is to evaluate the efficacy and safety of growth hormone therapy in patients with head injuries and growth hormone deficiency. CSP 2018 is double-blind, placebo-controlled trial where the patient nor the local site research team will know who is receiving the study drug or placebo; Only the study s Centralized Endocrinologist will have regular access to the treatment assignment. Patients will be randomized at a 1:1 ratio into one of the two groups: active growth hormone replacement therapy or placebo given daily for 6-months. The study s primary endpoint is Quality of Life, as measured by the Adult Growth Hormone Deficiency Assessment (AGHDA-QOL) questionnaire. The study s estimated duration is 39 months: 33 months intake + 6 months follow-up; the study s requisite sample size is 172 participants. The primary objective of CSP 2018 is to determine the efficacy of growth hormone treatment versus placebo on quality of life (QoL) as measured by the mean difference in QoL scores. The secondary objective is to investigate the effects of growth hormone treatment on cardiometabolic risk factors including lipids and highly sensitive C-reactive protein (hs-CRP) after 6-months of treatment. Cardiometabolic risk factors are important to assess because elevated lipids and CRP are associated with poor health outcomes. The primary biomarker of interest in titrating study therapy is Insulin-like Growth Factor 1 (IGF-1). Potentially eligible Veterans will be measured for IGF-1 once during the screening process; randomized participants receiving study therapy will be measured for IGF-1, 5 times during the study. Note that IGF-1 is the particular biomarker that has both the greatest relevance to our study design, and the most intensive logistics in obtaining and routing results: IGF-1 value must be known only to the Centralized Endocrinologist post-randomization. IGF-1 values will be used to titrate the study therapy. Background Adult growth hormone deficiency (AGHD) is recognized as a complication in patients with moderate to severe traumatic brain injuries (TBI). Specialized blood tests are required to diagnose AGHD. Growth hormone and IGF-1 measurements are widely used in the diagnosis and management of GH disorders. Therefore, it is imperative to obtain accurate and precise measurements of these hormones. Insulin growth factor-1 is a hormone secreted by the liver. Growth hormone regulates the secretion of IGF-1 by the liver, and the concentration of IGF-1 in the blood has been found to be directly proportional to the concentration of GH. Because of this relationship, IGF-1 will be used to titrate growth hormone replacement therapy and monitor GH levels throughout the study. There are multiple assays GH and IGF-1 assays currently available. The heterogeneity of analytes and the lack of uniformity in calibrator materials creates considerable differences between GH and IGF-1 results. The Growth Hormone Research Society, the International Society for IGF Research, and the Pituitary Society recognize the need to harmonize assay standards and have published GH and IGF-1 standardization guidelines. GH assays must meet the World Health Organization (WHO) 98/574 standard, and laboratories should use internal quality control materials independent of those provided by the assay manufacturer. The lab should also participate in accredited proficiency testing and external quality assessment program using materials that have been proved commutable at a national or international level. Two of the most critical blood tests for this study are the GH assay because it is used to establish diagnosis for inclusion in the study, and IGF-1 because it is used to diagnose and monitor GH throughout the clinical trial. Therefore, finding a contract laboratory who meets the rigorous standards set forth by the GH Research Society is of utmost importance. Given the many and varied biomarkers being collected in CSP#2018, and the potential complexity in coordinating processing and data integration from multiple facilities, study leadership prefers to contract all biomarker processing to a single vendor, ideally at a single processing site. A central laboratory is necessary to reduce variation across sites and to standardize the measurement over the four-year study: small differences in IGF measurement can significantly affect the interpretation of the study therapy, and thus the titration. The variations in biomarker assays at local labs is well-recognized and even small errors in calibration in some assays can have potentially major consequences for study integrity. Veterans will also undergo additional blood tests to rule out other hormonal disorders and/or medical conditions that are contraindicated in this trial. Among those labs is testosterone. Testosterone is an important measure because hormonal dysregulations must be addressed prior to enrollment in the trial, and administration of growth hormone may cause alterations of testosterone. Thus, monitoring testosterone before and throughout the trial is critical. Testosterone is present in the body in multiple forms: testosterone bound to sex-hormone binding globulin (SHBG) and albumin and the rest is unbound testosterone (also known as free / bioavailable testosterone). Total testosterone may be insufficient for diagnosis of mild abnormalities of testosterone homeostasis. Thus, additional measurements of free testosterone is recommended. However, because this test is more specialized than the ordinary total testosterone count, not all laboratories perform this assay. In fact, many VA medical centers outsource testosterone to other labs. Table 1 provides a comprehensive list of all the blood tests for CSP and collection schedule. Although many of the other screening and safety labs required for the study are routine, the logistics of having each site submit samples to multiple labs is extremely cumbersome. Further, lab samples in a clinical trial should be processed by a single laboratory to ensure standardization of results and specimen processing techniques. Scope and Methodology Due to the complexity of endocrine stimulation tests (e.g., Macrilen stimulation test to assess AGHD and ACTH stimulation test to assess adrenal insufficiency), the screening labs are broken up into two visits. At the first screen visit, Veterans will undergo basic routine labs such as complete blood count (CBC), complete metabolic panel (CMP), and Hemoglobin A1c. Cardiometabolic risk factors (lipids, in particular low density lipoprotein, LDL, and hs-CRP) will also be collected at screen visit. Because cardiometabolic factors are stable for at least a month, collecting them at screen visit will satisfy the baseline measure of the trial. Patients who clear the first screen visit will then be scheduled for the endocrine testing visit (endo visit) where the rest of the labs will be collected. Those who are diagnosed with AGHD and meet all other inclusion criteria will be randomized into the 6-month treatment trial. Table 1 (below) depicts the blood test schedule for CSP 2018. CSP 2018 plans to randomize 12 patients per site over the course of three years (equivalent to 4 patients randomized each year). To randomize 4 patients a year, it is estimated that 40 patients will be screened annually, per site (120 Veterans screened at each site over the course of three years). Tables 2 and 3 show the projected number of patients per site and for the entire project, respectively. Table 2. Estimated Annual and Cumulative Enrollment, Per Site Table 3. Annual and Cumulative Enrollment for Entire Clinical Trial Number of Patients (Entire Project) 4 Year Total Per Site # of Sites Total N= Screened 120 20 2400 Randomized 12 20 240 To calculate the quantity of each test, the labs collected at screen visit are multiplied by the annual number of expected participants, per site. Labs Collected at Screen Visit Only # of visits # of patients (per site) Annual Qty (per site) Total (per site) LH 1 40 40 120 FSH 1 40 40 120 Estradiol 1 40 40 120 Prolactin 1 40 40 120 ACTH 1 40 40 120 Cortisol 0, 30 60* 1 40 40 120 GH, 4 timepoints* 1 40 40 120 HbA1c 1 40 40 120 Lipids (LDL) 1 40 40 120 hs-CRP 1 40 40 120 CBC 1 40 40 120 CMP 1 40 40 120 Testosterone 1 40 40 120 FT4 1 40 40 120 TSH 1 40 40 120 IGF-1 1 40 40 120 Cortisol AM** 1 40 40 120 * Refer to lab. Billing for blood samples submitted for ACTH and GH stimulation tests vary by lab. It is important to note that some labs charge a fixed amount for the test while others charge per specimen. As of the time of drafting this SOW describes a study size of 20 sites. This, and related parameters, may change. We will provide timely updates as appropriate. ** Cortisol AM is different than Cortisol 0, 30, 60. Lab Test Abbreviations: LH = Luteinizing Hormone FSH = Follicle Stimulating Hormone ACTH = Adrenocorticotropic Hormone GH = Growth Hormone HbA1c = Hemoglobin A1c LDL = Low Density Lipoprotein hs-CRP = High sensitivity C-reactive protein CBC = Complete Blood Count CMP = Complete Metabolic Panel FT4 = Free Thyroxine TSH = Thyroid Stimulating Hormone IGF-1 = Insulin Growth Factor I In addition to the screen labs, the following labs will be ordered for patients randomized into the treatment trial. Quantity is calculated by multiplying the number of visits the test will be collected (during treatment phase) x number of patients, per site. Labs for Randomized Patients # of F/U visits # of patients Annual Qty (per site) Total (per site) Testosterone 5 4 20 60 FT4 5 4 20 60 TSH 5 4 20 60 IGF-1+SDS (blinded) 5 4 20 60 Cortisol AM 5 4 20 60 CBC 5 4 20 60 CMP 5 4 20 60 HbA1c 2 4 8 24 Lipids 2 4 8 24 hs-CRP 2 4 8 24 Description of Tasks, Associated Deliverables and Pricing The contracted lab must satisfy the following criteria: The growth hormone (GH) assay shall be a validated immunochemiluminometric assay standardized to World Health Organization (WHO) recombinant GH calibration standard WHO 98/574. The GH assay shall be compliant with the recommendations on assay standardization set forth by the Growth Hormone Research Society. Shall report standard deviation score (SDS) for IGF-1. Shall be able to provide references on how they derive the standard deviation score for IGF-1. Shall offer total, free and bioavailable testosterone. Specimen shipped to processing facility, utilizing study identifiers in lieu of Personal Identifiers Single account number on all (vendor provided) requisition forms Vendor shall provide blood tubes appropriate for collection that possess unique barcodes, which can be used to create a crosswalk at the site between the tube and any PHI Vendor personnel and laboratory shall be compliant with all applicable laws and regulations Lab must be Clinical Laboratory Improvement Amendment (CLIA) approved. Pricing: Lab Price per Each LH 1 $ FSH 1 Estradiol 1 Prolactin 1 ACTH 1 Cortisol 0, 30 60* 1 GH, 4 timepoints* 1 HbA1c 1 Lipids (LDL) 1 hs-CRP 1 CBC 1 CMP 1 Testosterone 1 FT4 1 TSH 1 IGF-1 1 Cortisol AM** 1 ** Cortisol AM is different than Cortisol 0, 30, 60. Reporting Requirements The contracting laboratory must make the test results available to the research team within 5-10 business days from submission date. Result reporting functionalities such batch reporting, exporting results as CSV file, direct input into iDataFax is preferred but not mandatory. The web portal shall be able to export the data; just showing the data without the ability to download is not acceptable. The CSPCC requests a representative sample of results for the purposes of developing the data management platform. Minimum report data must include: Specimen ID, date received, date tested, result/value (in units designated in this SOW). Calibration, frequency, and validation of instruments shall be submitted in the vendor s quality control plan. Study Leadership shall be informed in the event that usual and customary procedures change due to any circumstance or unforeseen event, to include lab closures. OTHER CONSIDERATIONS While Study Leadership expects that sample volume should be relatively constant throughout the study, Vendor shall be flexible with sample flow due to shifting recruitment patterns. All responses shall include information which demonstrates equivalency (as a minimum) to the specifications outlined in the solicitation. Delivery FOB Destination to: Michael E. DeBakey VA Medical Cener Baylor College of Medicine (BCM 350) One Baylor Plaza Houston, TX 77030 The applicable provisions and clauses are located on attached solicitation document: Additional contract requirement(s) or terms and conditions determined by the contracting officer: Set Aside Cascading set-aside procedures. Any award resulting from this solicitation will be made using a cascading set-aside order of precedence as follows: 1. In accordance with FAR Subpart 19.1405 and VAAR Subpart 819.7005, any award under this solicitation will be made on a competitive basis first to an eligible Service Disabled Veteran Owned small business [SDVOSB] concern provided that the conditions of 38 U.S.C. 8127(d) are met (the VA Rule of Two) whereby the Contracting Officer receives adequate competition of two or more small business concerns owned and controlled by Veterans, and that the award can be made at a fair and reasonable price that offers the best value to the United States. 2. If there is inadequate competition for award to an SDVOSB concern, the SDVOSB set-aside shall be withdrawn and cascaded to the next contracting order of priority in accordance with VAAR 819.7004, which is Veteran Owned Small Businesses (VOSB) and conducted in accordance with the procedures set forth in VAAR 819.7006 provided that the conditions of 38 U.S.C. 8127(d) are met (the VA Rule of Two) whereby the Contracting Officer receives adequate competition of two or more small business concerns owned and controlled by Veterans, and that the award can be made at a fair and reasonable price that offers the best value to the United States. 3. If there continues to be inadequate competition between SDVOSB and VOSB concerns, the cascading will continue through the contracting order of priority in accordance with VAAR 819.7004 and FAR 19.203. If the contracting officer determines that offers from small business concerns do not meet the solicitation requirements in terms of technical acceptability, past performance, and fair market price, the small business set-aside[s] will be withdrawn and award will be made on the basis of full and open competition. Adequate competition: Adequate competition shall be deemed to exist if At least two competitive offers are received from qualified, responsible business concerns at the set-aside tier under consideration; and Award could be made at fair market price as determined in accordance with FAR 19.202-6. The VA contracting officer reserves the right to consider competitive proposals submitted from all responsible offerors (including large businesses) in determining the fair market price. Due date and submission of quotes: The quotes are due on 1/24/2022 at 10:00 AM (EST) and shall be directed electronically to contact@example.gov. Quotes shall be marked with the solicitation number. Information regarding the solicitation can be addressed to the Contracting Officer, Michael Haydo, contact@example.gov