MODIFICATION
D -- NCI PK/PD Modeling: Erythropoietin & Darbepoietin Technical Quesitons and the Government's Response
- Notice Date
- 6/13/2003
- Notice Type
- Modification
- Contracting Office
- Minerals Management Service GovWorks (Franchise) 381 Elden Street, = MS 2500 Herndon VA 20170
- ZIP Code
- 20170
- Solicitation Number
- 1435-04-03-RP-72743
- Response Due
- 6/23/2003
- Archive Date
- 6/12/2004
- Point of Contact
- Shanda Georg Business Specialist 7037871758 Shanda.Georg@mms.= gov;
- E-Mail Address
-
Email your questions to Point of Contact above, or if none listed, contact the IDEASEC HELP D= ESK for assistance=20
(EC_helpdesk@NBC.GOV)
- Small Business Set-Aside
- N/A
- Description
- Questions received within the date and time specified and the governm= ent's response. 1. What is the anticipated timeline for awarding the contract? Government Response: Mid July, 2003. 2. Would you consider receiving a proposal with increased timelines and a= description of the anticipated issues to be encountered and the reasons fo= r delay? Government Response: We would consider it, but a proposal able to meet the = timelines will likely be more highly rated unless the issues raised suggest that any offeror should have recogni= zed that the timelines are unachievable. 3. Do Amgen and Ortho Biotech have both the protocols and the data for ea= ch study prepared and ready to be transferred? Government Response: Yes 4. Could you please provide a detailed synopsis of each trial available, = including a description of the relevant data collected in each? For exampl= e, describe the data available for analysis in the following manner: Phase= of each study, dosing history and regimen in each study, type(s) of malign= ancy, what chemotherapy treatment(s) and=20 regimen(s) the patients have received, times and amounts of blood transfusi= ons, number of patients/subjects, number of biological samples collected an= d frequency of collection: which analytes are available (e.g., erythropoiet= in, darbepoietin), RBC, precursor cell counts/reticulocyte counts, iron the= rapy, ferritin, concomitant medications, etc. Government Response: This level of detail will only be provided to the awa= rded contractor, under confidentiality. Inventory and data qualification o= f the available studies to select those that are pertinent to this project = will be part of the project. Data may be made available from at least 5 st= udies for each agent, which range from dose finding to phase III studies, i= n a variety of cancers, including regimens that are platinum and non-platin= um containing. About =BC of patients are estimated to have required transfu= sions. Clinical data may be available for approximately 1000 patients, wit= h 510 samples for about 200 patients for epo levels,. Reticulocyte counts a= re available for only a minority of patients in more recent studies, as is = data regarding iron stores. The awarded contractor will be able to review a= paragraph for each possible study data source and then enter a dialog with= each co-sponsor to identify more details regarding the data sets that will= actually be used in the model. 5. What is the format of the data, e.g., SAS transport format, Excel, etc= .? Are the data in clinical database format or in analysisready datasets? Government Response: In preparing your proposal, assume that the data are = in a common clinical database format, not in datasets ready for NONMEM or o= ther population PK program 6. Could you provide further clarification regarding Page 4, TASK I, Sect= ion A, 2, 1) of the Solicitation ("coupling of erythropoietin elimination rate and erythropoietin sensitivity (through = number of erythropoietin receptors)")? Government Response: There is some evidence that epo is cleared via bindin= g to its receptors, and the size of the erythron (the hematopoetic "organ")= both alters clearance rate and the ability to respond to epo. This establ= ishes a potential non-linearity where the response to epo can be altered by= both the responsiveness of the erythron in the face of chemotherapy and th= e size of the erythron. Please consider the complexities of evaluating the = importance of these potential non-linearities and feedback mechanisms in yo= ur model. 7. Page 8, TASK III, Section 2 references dosage regimens which would be = provided for the simulations: Are you anticipating a series of simulations= which utilize a distribution of chemotherapy treatments paired with one sp= ecific hematopoietic growth factor regimen OR a series of simulations utili= zing pairs of a specific chemotherapy regimen and a specific hematopoietic = growth factor regimen? Government Response: We envision an initial simulation evaluating two chem= o regimens (one with, one without a platinating agent), and several differe= nt regimens for growth factor, as described in the task - e.g., a minimum o= f 3 different doses and 2 dosing intervals for each agent. 8. For the simulations, should a set number of dosage regimens be planned= (if so, what number?) or should the cost be provided on a per dosage regim= en basis?=20 Government Response: See response to question 71 The precise parameters of= the initial model are difficult to estimate without exploring the paramete= r space and potential models. It seems unlikely that there is a linear rel= ationship between the cost of this trial and the possible need for addition= al explorations of effects of dose magnitude, dose frequency, and outcome a= ssessments after evaluation of the initial simulation experiment. Once the= re is a satisfactory model, additional exploration may be in order, so it's= difficult to estimate the number of additional simulation experiments in a= dvance. For the purposes of estimating the contract costs, assume 12 treatm= ent regimens (3 doses and 2 dose intervals) and 2 chemotherapy regimens for= the initial effort, as well as approximately 5 outcome measures (eg, % of = patients who increase hgb >12 within 8 weeks, or transfusion requirements).= One or more additional simulation experiments may subsequently be warrant= ed to fully define the dose/schedule - response surface. 9. Page 8, TASK III, Section 4: is this step intended to be performed on = the base model used for generating the simulations or every simulation scen= ario? Government Response:. Sensitivity analysis should be performed on what is c= onsidered to be the most crucial conclusions. For example, if the initial = simulation experiment permits an estimate of the ratio of the ratio of the = weekly doses of the two agents, each producing a hemoglobin rise of 2 withi= n 8 weeks in at least 50% of patients, what is the sensitivity of the dose = ratio to specific model assumptions? We estimate that there might be a half= dozen such crucial conclusions (eg transfusion rate) and a half dozen crit= ical model assumptions that might require testing. 10. Does the limitation regarding the provision of separate reports to eac= h commercial sponsor preclude the pooled modeling of the erythropoietin and= darbepoietin, i.e., does confidential data refer to raw and analysis data = only or does it also include modeling results? Government Response: The model should be developed using all the appropria= te data from both corporate sponsors - we want one model that responds to = both agents. . The competitor company will not be provided with drug spec= ific parameters or simulated responses for any but the drug they provide. = The general outline of the biology represented in the model will be availa= ble to both sponsors. 11. We would appreciate clarification of the conflict of interest requirem= ents. If either of the two companies=20 (Amgen or Ortho Biotech Products) identified in the RFQ are former or curre= nt clients of our company, are we precluded from qualifying as a responder = to the RFQ. Government Response: As a condition of award the Contractor must have no r= ecent prior or current (at the time of award) financial interests or relati= onships with either of the companies (Ortho Biotech Products, L.P. and Amge= n, Inc.) or their affiliates that could lead to a perceived or real conflic= t of interest. In addition, as a condition of award the Contractor must ag= ree that it will acquire no financial interest or relationship with either = of the companies (Ortho Biotech Products, L.P. and Amgen, Inc.) that could = lead to a perceived or real conflict of interest, for a period of 6 months.= This period of restraint is necessary to avoid the circumstance of unfair = competitive advantage or potential bias. If Amgen or Ortho Biotech Product= s, or subsidieary is a current client, it is a conflict of interest.
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