Analgesic Clinical Trials

The Food and Drug Administration is seeking a contractor for Analgesic Clinical Trials Project (ACTP): Prediction of Treatment Response REQUEST FOR QUOTE (RFQ). This announcement constitutes the only solicitation and a written solicitation will not be issued. Requirements: II. Project Title: Analgesic Clinical Trials Project (ACTP): Prediction of Treatment Response III. Background: In March of 2004, the U.S. Food and Drug Administration (FDA) released a white paper entitled "Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products. This report called for research to develop and validate new tools and methods for testing new medicines on the "critical path" from the laboratory to the patients. This initiative is called the Critical Path Initiative. Under the auspices of this initiative, FDA in conjunction with academia launched an initiative in August 2006 called the Analgesic Clinical Trials Project (ACTP) focused on identifying scientific gaps in the design, implementation and interpretation of clinical trials of acute and chronic analgesic drug products, and on implementing projects that will bridge these gaps. Under the ACTP, FDA and academia are working to coordinate and support a series of research projects, all focused on analgesic clinical trial design and product development. Through the ACTP, FDA and academia are identifying scientific gaps in the aforementioned areas, prioritizing projects based on public health needs and implementing them through the leveraging of resources and technical expertise from multiple partners. In spite of the enormous advances in drug development over the past two or three decades, (e.g., drugs that cure cancer, biologic drug products that halt the progression of rheumatoid arthritis), the development of novel analgesic drug products has seriously lagged behind. Indeed, to this day, the only analgesic drug products that are used widely and successfully are opioids, acetaminophen and the non-steroidal anti-inflammatory agents (NSAIDs), all of which have serious, potentially life-threatening toxicities even when used properly. While there has been exploration at the earliest stages of drug development, there has been wide'-spread reluctance on the part of the pharmaceutical industry to take novel products further into development. This is in no small part due to the often daunting task of demonstrating the efficacy of analgesics in clinical trials. Many experts in analgesic drug development believe that it is the design of the clinical trials that is - at fault in this situation, and that better trial designs will yield more successful results. This hypothesis is certainly supported by the frequent failures of clinical efficacy trials of opioid drug products, considering the well established effectiveness of these products from literally thousands of years of clinical experience. The FDA wishes to engage a contractor to develop a model for prediction of the placebo response rates in analgesic clinical trials, and the relationship of response rates on study outcomes. The FDA wishes to engage a contractor to determine the effect on study outcome of statistical imputation techniques on analgesic study outcomes. Independently and not as an agent of the Government, the contractor shall furnish the necessary personnel, materials and services necessary for performance of the work as described below. All data and outcomes associated with this scope of work shall be provided to and go through the Project Officer (PO), to the FDA. A final report shall be prepared by the contractor that summarizes the deliverables of this contract. The contractor shall, in collaboration with FDA staff, identify analgesic trials and datasets for creation of a harmonized dataset, and establish a common data variable configuration and links to the appropriate data fields in each dataset. This harmonized dataset shall be used to achieve the contract objectives, as stated above. Reporting Requirements and Deliverable Items: The activities and deliverables under this Statement of Work must be completed during a one year period from the date of execution of the contract. Any extension (including No Cost Extensions) of this timeline must be done in writing and must be authorized by the PO. Deliverable Weeks After Start of Contract 1. Kick-off Meeting with FDA Within 2 weeks 2. Project Workplan with identification of the appropriate clinical studies and databases 6 weeks 6. FDA briefings at key milestones, per the Workplan 6 weeks to 10 months 7. Final meeting with FDA including draft report 10 months 8. Final report 12 months The contractor shall then further evaluate the data in the aforementioned harmonized dataset in an attempt to define potential novel methods of analyzing these data that will provide evidence of efficacy when it truly exists, and avoid false negative as well as false positive results. Potential novel analyses include, but are not limited to: - Placebo response analysis - Factors determining placebo and treatment response rated in analgesic clinical trials - Imputation strategy analysis - Determination of the effect on study outcome of alternative analysis techniques for handling missing data on the cumulative proportion of responder analysis (CPRA) and other more standard outcome analysis techniques The contractor shall lead the development of appropriate publication/s and/or report/s, in collaboration with FDA staff on summaries and other finding from this Statement of Work, the number and content of which shall be mutually agreed upon by the contractor and the FDA Project Officer. Criteria for Acceptance of Deliverables: The contractor shall implement and maintain a quality assurance system to ensure the product integrity of all deliverables that meets or exceeds the requirements established in this SOW. Final inspection and acceptance of all work performed, reports and other deliverables shall be performed at the place of delivery by the PO. [General quality measures, as set forth below, shall be applied to each work product received from the contractor under this statement of work. - Content-Work products shall be inclusive of all items mentioned in the objectives and scope along with content identified in [or by] the assessments. - Accuracy Work Products shall be accurate in presentation, technical content, and adherence to accepted elements of style. - Clarity Work Products shall be clear and concise. Any/All diagrams and graphics shall be easy to understand and be relevant to the supporting narrative. - Consistency to Requirements All work products must satisfy the requirements of this statement of work. - File Editing All text and diagrammatic files shall be editable by the Government. - Format - Work Products shall be submitted in hard copy (where applicable) and in media mutually agreed upon prior to submission. - Timeliness Work Products shall be submitted on or before the due date specified in this statement of work or submitted in accordance with a later scheduled date determined by the Government. VIII. Duration of Project: The activities and deliverables under this Statement of Work must be completed during a one year period from the date of execution of the contract. Any extension (including No Cost Extensions) of this timeline must be done in writing and must be authorized by the PO. XI. Evaluation Criteria A. General - The offeror shall submit a technical proposal that covers the type of work described in Section V, Scope of Work. The offeror shall submit a business proposal that includes ceiling hourly rates (unloaded) for all labor categories. Proposals received will first be evaluated from a technical standpoint without regard to proposed costs. Those proposals that are considered technically acceptable will be evaluated from a financial and management standpoint. B. Technical Evaluation - This evaluation will be based upon the thoroughness of the proposal submitted. The offeror should show an understanding of the objectives and offer a logical program for their achievement. The following factors will be weighted as indicated in establishing a numerical rating for all technical proposals submitted. Evaluation Criteria Weight (Total of 100 points) 1) Personnel Experience Total 40 points Factors to be considered include: o Education, skills and experience of the proposed staff with respect to the tasks delineated in the Scope of Work o Availability of proposed resources to commit to the contract o Experience outlined under Special Terms and Conditions 2) Organizational Experience Total 20 points Factors to be considered include: o Offeror's expertise in analgesic clinical trials o Past performance and participation in similar efforts o Degree to which the Offeror's organization is able to support the efforts proposed o Experience outlined under Special Terms and Conditions 3) Technical Approach Total 20 points Factors to be considered include: o Plan for how the Offeror will staff and execute the project o Experience outlined under Special Terms and Conditions 4) Data Access and Resources Total 10 points Factors to be considered include: o Capability to collect primary data and ability to work with databases of varying formats and sizes o Ability to work with both quantitative and qualitative data o Experience outlined under Special Terms and Conditions 5) Project Management Total 10 points Factors to be considered include: o Demonstrated ability to manage projects of this kind o Experience outlined under Special Terms and Conditions XIV. Special Terms and Conditions 1) Personnel Experience a) Offeror shall demonstrate that it has medical personnel with extensive experience in (i) performing analgesic clinical trials (ii) examining such data, and (iii) devising innovative methods for clinical trials iv) use of modeling and development of specialized statistical programs for prediction of treatment response, and (v) cumulative proportion of responder analysis (CPRA). These personnel should be considered experts in the field of pain medicine and research, as evidenced by adoption of their innovations as standard methods by the field, service on editorial boards of leading journals that publish pain research, consultancy for industry and/or the FDA, scientific awards, NIH grants, and publications of journal articles and/or text books, and b) Offeror shall demonstrate that it has statistical personnel with a special interest in the type of data, clinical considerations and challenges of pain studies, and who can provide sustained attention to this project over its duration. The statistical personnel should have doctorate-level training in biostatistics and pharmacoepidemiology, have prior experience in the use of large databases and methodology of signal detection in large databases, and have demonstrated ability to work with large and multiple datasets. The statistical personnel should also have experience in the development of non-ignorable missing data models for longitudinal data with complex - missingness patterns, and c) Offeror shall demonstrate that it is nationally recognized as a major academic research institution, as demonstrated by composition to include multiple medical and graduate training institutions, and a dedicated center for the study of epidemiology and biostatistics. National recognition as a major pain research center should also be demonstrated by the number and scope of pain-related and anesthesia-related NIH grants, institutional grants for clinical research training, and authorship of multiple journal articles and text books, and d) Offeror shall demonstrate that it employs the personnel requisite to perform high caliber qualitative and quantitative analyses over the range of studies and evaluations presented in Section V, Scope of Work. 2) Organizational Experience Offeror shall demonstrate its expertise in analgesic clinical trials. Expertise shall be evidenced by such factors as previous conduct of pain trials, development of innovative analgesic trial designs, creation of novel outcome measures and statistical analyses of analgesic trial data, as well as extensive publications, citations and awards for work in analgesic clinical trials. Offeror shall demonstrate its unique biostatistical interest and analytical abilities in analgesic pain trials. Offeror shall demonstrate the ability for liaison with contracting organizations, including operational staff, as appropriate. 3) Technical Approach The offeror shall demonstrate expertise in development of prediction models for treatment response, statistical methods for handling of missing data in analgesic trials, parametric and non-parametric tests, cumulative distribution function analyses, and identification and selection of appropriate statistical methodologies for the required data analyses. 4) Data Access and Resources Offeror shall demonstrate primary data collection capability and the ability to work with databases of varying formats and sizes. Ability to work with both quantitative and qualitative data shall be emphasized. 5) Project Management Offeror shall provide information on the administration of the project tasks. This should include management plans, methods for implementing, reviewing and effecting interim adjustments and corrections, and quality control and cost control procedures. XV. Identification and Disposition of Data Offeror agrees not to disclose any such data to any persons except FDA employees having a need to know for the conduct of FDA business. REQUEST FOR QUOTE (RFQ) Any firm that believes it is capable of providing the required service as stated herein may submit a proposal to document its ability to provide the required services, which will be considered if received by the fifteenth (15th) calendar day following the appearance of this announcement. A determination to compete this procurement based on a response to this notice is solely within the discretion of the Government. All responses or questions regarding this posting must be in writing and can be sent via email to joseph.pishioneri@fda.gov. No phone calls will be accepted. This sole source procurement will be awarded as a simplified acquisition for commercial items in accordance with FAR Subpart 13.5.