Sources_Sought_Notice_FINAL.pdf

General Information:

Document Type: Sources Sought Notice

Release Date: March 28, 2014

Response Date: April 14, 2014 at 12:00 local time via email to william.lee@fda.hhs.gov

Contracting Office Address: Food and Drug Administration, 5630 Fisher Lane, Rockville, Maryland 20857; Attn: William Lee, Contract Specialist

Description of Services: Scientific Program to Support

Pharmacoepidemiologic Investigations of Safety Related Issues of Marketed Drugs, and Evaluations of Risk Communications and Management Programs.

This is a Sources Sought Notice to identify the capabilities of the marketplace of all interested parties.

DISCLAIMER

This notice is for planning purposes only and shall not be construed as a solicitation or as an obligation on the part of the Food and Drug Administration (FDA) for any future solicitation. No official solicitation exists; therefore, please do not request a copy of a solicitation. If in the future an official solicitation is released, there is no guarantee that sources responding to this will be included on the source list.

Telephone inquiries will not be accepted.

Background

A vital part of FDA and CDER’s mission is to protect the public health. The Center for Drug Evaluation and Research Office of Surveillance and Epidemiology (OSE) contributes to promoting the safe use of FDA regulated drug products by the American people through pharmacoepidemiological research. In response to reports from the Institute of Medicine (IOM), FDA is authorized by FDA Amendments (2007) Act, followed by the recent enactment of PDUFA V and the FDA Safety and Innovations Act (FDASIA) (2012 that provide FDA with the authority to develop collaborations with multiple private entities to obtain and expand database resources for providing advanced analyses of drug safety data to improve the quality of postmarket risk/benefit analyses, gain access to outside expertise, and enhance the ability of FDA to make timely assessments of drug safety data. CDER seeks to establish collaborations between FDA and researchers with recognized expertise in relevant areas of pharmacoepidemiology expertise pertaining to drug safety. In addition, FDA is interested in collaborations that would provide access to electronically linked bio-bank data and coupled with pharmacogenetics expertise experienced working with the biobank linkages. The FDA drug product safety program resources should include population-based pharmacoepidemiological data sources, linkages to laboratory test results, vital status such as the National Death Index (NDI), and other types of large electronic, observational data resources to evaluate class effects of drugs in targeted pharmacoepidemiologic studies. The research supports evidence-based approaches to quantify product risks and test hypotheses based on signals identified as potential postmarket drug safety issues of regulatory importance.

In addition, consistent with FDA Safety and Innovations Act (FDASIA) (2012) there has been a growing emphasis on the need to incorporate social and behavioral science methods into product safety research such as pharmacoepidemiology to optimize the impact and efficiency of FDA risk communications. In addition, comprehensive data are needed to determine whether drug safety is improved by evaluation of the increasing numbers of risk management efforts. The enactment of the Food and Drug Administration Safety and Innovation Act under Section 1124 (as well as Section 1138) authorizes the FDA to conduct science-based FDA risk communications: “To facilitate the translation of science-based regulatory decisions and information into public health gains, FDA must strengthen social and behavioral sciences in the areas of understanding and reaching diverse audiences, ensuring audience comprehension, and evaluating the effectiveness of communications in changing behaviors related to the use of regulated products.” Reaching diverse audiences includes enhancing focus on understanding safety characteristics in minority populations, the medically underserved, and populations with low literacy and health literacy skills, all of which are important gaps to address.

Improving methods to study FDA risk communications in defined epidemiological new-user populations will enhance these efforts.

Purpose

The purpose of the FDA Scientific Pharmacoepidemiologic Research Program is to establish collaborations that would provide access to a range of different types of US population-based data resources to conduct timely studies as drug safety issues of heightened interest arise. Such collaborations would allow FDA scientists the ability to leverage existing healthcare data for pharmacoepidemiology studies that may be enhanced by application of pharmacogenetic, social science, and/or pharmacologic methods to contribute to evidence-based assessments of risk management tools, special populations, and even causes of medication errors to advance the FDA regulatory science mission. FDA does not anticipate using the contract as a vehicle to purchase data or access to the data.

Objectives

The primary objectives of the collaborative FDA Pharmacoepidemiologic Research Program are to:

• Enable timely access to United States population-based data sources to conduct drug safety studies in a collaborative arrangement with existing pharmacoepidemiologic research programs. For in-depth studies with demonstrated feasibility, the ability to link electronically to systematically collected data DNA biobanks, laboratory test results, nonprescription drug dispensing, disease or outcome registries, BMI, tobacco use, alcohol and other psychoactive substance use, family medical history, and expert random sampling, interview and survey capabilities from identifiable new user populations are of particular interest;

• Establish a collaborative arrangement with recognized pharmacoepidemiologic research programs for the purpose of evaluating the effectiveness of FDA risk communications and other risk management efforts using large, nationally representative population data sources;

• Develop research collaborations that link pertinent systematically collected information for special populations, i.e., ethnicities, children, pregnant women, other medically underserved populations for conducting drug safety studies, particularly in large nationally representative databases;

• Obtain expert scientific collaboration and/or consultative support on advancing methods and the use of electronic health data resources for conducting innovative, informative pharmacoepidemiologic research of scientific importance through requests for information communications, annual meetings, and annually updated summaries of data resources in addition to development and conduct of feasibility assessments and in-depth studies.

Scope of Work

Independently, and not as an agent of the Government, the Contractor shall provide the required personnel, materials, and services to perform the work as described below:

Task 1: Core Data Requirements

a) High Quality Technical Assets

Evidence of postmarket drug safety from real world settings can help address critical regulatory science knowledge gaps when the quality of the data is high and the methods are rigorous. The nature of pre-approval drug product testing does not ensure that the drug will reach the market without potentially serious unknown risks. And data on drug effects in special populations is limited, including medically underserved minorities, pregnant women, nursing home residents, and pediatric populations. Postmarket drug safety research must be multi-dimensional reflecting the interaction of numerous biological factors in a complex multi-media imbued environment influenced by multiple stakeholders. The evaluation of quality of evidence of pharmacoepidemiologic research to address each question requires understanding the appropriateness of the patient population; ascertainment of drug exposure; validity and completeness of health outcome identification; use of the most informative study design and sets of analyses to answer the questions of interest while minimizing distortions of effect estimates by confounding and interactions.

b) Continuous and Complete Data Access

The Contractor shall have continuous access to current and frequently updated electronic healthcare data resources containing detailed patient-level health encounter data from the United States of America. The limitations, as well as strengths of the data resources need to be clearly identified. The core data requirements for the data resource shall be a large nationally or regionally representative computerized system linking each patient to all required relevant medical care data including electronic health records with enrollment status. Health systems that are not nationally representative should offer highly detailed health information with unique features conducive to production of valid, high quality in-depth research. Highly desirable data include smoking status and body mass index (BMI), extensive long-term and highly detailed drug product exposure data, diagnoses over the lifespan, past medical history, family health history, and integrated coded inpatient and outpatient electronic medical record systems with all consultations and procedures, linkage to the National Death Index (NDI) and death certificates, and linkage to disease registries. Linkage of this data resource to additional information, including chronic disease or cancer registries, birth certificates, and birth defect registries is also required.

The Contractor shall be responsible for insuring that the data are HIPAA-compliant and de-identified to protect patient privacy for FDA use. FDA will require no patient-, provider-, or health plan-specific identifiers, although codes undecipherable to external parties to conduct randomly sampled selection for interviews and surveys is of interest. All research performed by the Contractor shall and must comply with standards for privacy of individually identifiable health information and protect the rights of human subjects in research.

c) Patient-level Data Required for Analyses

The data resource shall meet FDA’s need to access patient-level data describing health encounters and prescription drug use by individuals over time. The data resource shall have longitudinal data that shall be capable of following uniquely identifiable individuals (using encrypted patient identifiers) over time. Demographic information (e.g. age, sex, race/ethnicity), long-term health history, diagnoses and procedures, and healthcare utilization such as outpatient visits and hospitalizations shall be provided. Information on race/ethnicity shall, if available, be included accompanied by documentation of the origin of this information.

For each patient these data shall contain prescription drug and biologic product utilization information, including the generic and brand name of the product, strength, dosage form, days supply, all dates dispensed, initial/continuing therapy indicator, quantity dispensed, instructions for use (if available), indication for use (if available) and prescriber specialty.

The resource shall employ the use of a generally accepted, granular coding system for drugs and medical products, as well as for diagnoses and procedures. In addition, the Contractor shall have the ability to determine that the drug or biologic was dispensed to the patient, rather than just prescribed to the patient.

All patient medical diagnostic information shall be represented in the data resource and be complete, including diagnoses and procedures associated with all ambulatory, emergency, chronic or acute care setting visits and their dates, diagnoses and procedures associated with related hospitalizations and their dates, and laboratory test results and their dates. Medical diagnostic information required shall be systematically collected and complete at a minimum. Attributes of interest to FDA include linkage to data on DNA samples with broad consent in biobanks linked to longitudinal patient data, detailed data on family health history, smoking status, alcohol use, psychoactive substance use, as well as blood pressure measurements, height, weight, body mass index. While linkage to Electronic Health Records is preferred, the Contractor shall have the ability to access all inpatient and outpatient medical records for validating coded diagnostic data and access to outpatient medical records is required. The Contractor shall have the ability to contact a random sample of physicians and/or a random sample of patients/caregivers on an ad hoc basis for information beyond what is available in the data source (e.g., a survey to determine reasons for prescribing decisions, use of informed consent, use of nonprescription drugs and/or medical products, comprehension of consumer medication information, root cause analysis of a medication error).

Contractors shall collaborate with FDA Contracting Officer’s Representatives (COR) and scientists in developing the study design, which includes the statistical analysis plan.

Details of the collaboration will be determined for each Task Order by mutual decision of all collaborative parties. FDA encourages development of theme-based programs that address key knowledge gaps. The Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) is an example of linking medical data for mother-child pairs to facilitate the study of drugs used in pregnant women and the health outcomes of their babies across large populations. FDASIA lends authority to FDA to develop evidence-based approaches to assess the impact of FDA issued risk communications on patients and healthcare providers and effectiveness of FDA Risk Evaluation and Mitigation Strategies (REMS). Much prior research that has informed regulatory action has not been robust and developing more rigorous methodologies is fundamental to leveraging available data using approaches that will ensure valid results to enhance understanding.

Task 2: Feasibility Assessments

These are preliminary analyses designed to determine the number of patients utilizing a specific therapy, the patients’ ages and genders, and/or crude counts of outcomes of interest within the combined identified exposure groups, as well as the ability to validate outcomes to determine the feasibility of conducting a formal in-depth study. Information about the practicability of collecting additional patient-level information (estimated timelines, likely response rates, sample sizes, costs, etc.) or using other tools and unique resources such as linkage to biospecimen data with broad informed patient consent may be gathered at this stage as well. The Contractors may be able to provide unique expertise in areas critical to conducting high quality pharmacoepidemiologic research.

The benefit of the expertise to the regulatory science project of interest may be provided to FDA in a white paper to enhance work in this area especially with respect to generating the highest quality data possible in the data source utilized for the feasibility assessment. Feasibility assessments are negotiated with the contractors on a case-by-case basis and the results are submitted as written reports to FDA. Typical timelines for completion of feasibility studies are 4-12 months, depending on the complexity and innovation of the proposed study and given the existing infrastructure.

Task 3: In-depth Pharmacoepidemiologic Studies

These are usually large, single or multi-center pharmacoepidemiologic studies conducted in collaboration with FDA scientists (that either quantifies a product-specific risk or test hypotheses of regulatory interest. Depending on the question and the target populations, the optimal data source characteristics will vary. Depending on the complexity of the safety issue(s) the number of drugs and types of outcomes under investigation, and FDA’s programmatic needs, these studies may include some but not necessarily all of the following steps:

1. Development of a detailed protocol for an in-depth pharmacoepidemiologic study, in collaboration with the FDA Contracting Officer Representative (COR) and project advisory group (PAG) following requirements in the Scope of Work (SOW) that shall specify the agreed upon study design including definitions for exposure cohorts, outcome definition and validation; statistical analysis plan, and sensitivity analyses in collaboration with the FDA PAG; the design shall include the ability to satisfy OMB requirement for the Paperwork Reduction Act and all human rights protections through all Institutional Review Boards (IRB) in a timely manner;

2. Generation of de-identified analytical datasets and documentation for analysis at contractors’ site or for sharing with other sites and/or FDA, if considered necessary, under appropriate data-sharing agreements with full HIPAA-compliant protection of patient confidentiality;

3. Regular, routine communications with FDA collaborators on study progress;

4. Linkage to detailed electronic health records and/or accessible paper medical record retrieval for review and validation within the study population of interest in at least a subset of the data source and systematic linkage to the National Death Index in at least a subset is required;

5. Collection of additional physician- or patient-level information such as interview and survey data in the effort to evaluate FDA risk communications or conduct medication error studies such as root cause analyses; linkage to data from DNA biospecimens with broad consent for genomic analyses; laboratories and the results; pathology reports; imaging reports; systematic linkage to death certificates; cancer registries, chronic disease registries in an integrated health system;

6. Preparation of study progress report(s) and/or interim analyses; and

7. Communication of study results shall be through multiple mechanisms such as the final study report that may include a white paper, and presentations at FDA. The results may be published in peer-reviewed journals with FDA scientists who make scientific contributions to be listed as authors commensurate with their contributions to the work. The work will continue on the manuscript after the requirement is completed without any additional funding from FDA.

Task 4: Evaluation of FDA Risk Communications Management Programs

Includes evaluation of drug-specific and general risk communications and possibly other management strategies and tools. The type of evaluation desired will vary depending on the risk management program [or Risk Evaluation and Mitigation Strategy (REMS)].

There may be a need to evaluate compliance with specific components of the program process (e.g., laboratory testing prior to obtaining a restricted drug), or to evaluate the impact of the program on the health outcomes targeted by the program (e.g., minimizing hepatotoxicity). Although NDA and BLA sponsors generally conduct program evaluations, the Agency is conducting independent analyses of processes and programs that may include several drugs in the same class or several programs with similar goals.

Likewise, FDA will be the primary evaluator of general risk management tools (e.g. FDA risk communications or medication guides).

Task 5: Methodological research for regulatory purposes

Involves development of new methods specific to the quantification of safety risks or the evaluation of the impact of FDA risk communications for regulating pharmaceutical products and protecting the public health. Examples of these types of tasks include: a) developing prospective methods for improving the detection and analysis of adverse drug events, b) developing methods for utilizing ancillary data repositories (e.g.

pharmacogenetic, disease-specific, mortality), c) improving methods for validating drug exposures and adverse medical outcomes using electronic healthcare data, d) developing and/or utilizing methods for improving adjustment of analyses for time dependent exposure and confounding, and measured and unmeasured confounding factors, e) evaluating the impact on patients and healthcare providers of FDA issued risk communications.

Task 6: Theme-based Drug Safety Programs

Many special populations are often not well represented in any single population-based data resource. Special populations are those that might be considered particularly vulnerable with regard to drug safety issues because of numerous factors including, reduced access to health care and education, types of existing health conditions and the number and/or types of drug products routinely prescribed. Special populations can be defined by factors such as age (elderly, children), race/ethnicity, chronic disease (e.g.

diabetes, arthritis), reproductive stage (e.g., pregnancy) or drug exposure (e.g.

antiretroviral therapy, recombinant technology products); tobacco exposure. Theme-based Drug Safety Programs are research collaborations which link pertinent existing information for special populations or data characteristics (e.g., biobanks) within multiple data resources for the purpose of increasing sample size, and possibly the level of detail of information available. The goal of the linkage of multiple data sources is to achieve sufficient statistical power to study questions of regulatory interest to FDA, which may require ongoing collaboration between multiple sites. Tasks of this type will require creating standardized repositories of information on special populations within each site.

In the development of such repositories, one site will typically be designated as the lead for either pooling data or for developing common data structures and common analytical plans across sites. The sites, along with FDA, will determine the most appropriate center to be the lead for utilizing these repositories in a timely manner for specific drug safety investigations.

Capability Statement Format and Survey Instructions:

Responses that merely offer to perform in accordance with the requirements of the Scope of Work will be considered “Non-Responsive” and will not be reviewed.

Responses shall be:

Identified with Sources Sought number;

identified with the Name of Company;

no more than twenty (20) pages in length;

not submit marketing materials;

submitted to the email as indicated above.

FDA makes no implied or in fact contract by issuing this Sources Sought Notice.

Acknowledgement of receipt of responses will not be made, nor will respondents be notified of the FDA’s view of the information received.

CONTRACTOR CAPABILITY SURVEY

Please complete Part A, Questionnaire, describing your company’s capabilities;

Part B, Business Information and Part C, Estimated Dollar Range.

Part A. Questionnaire:

Provide the following information to demonstrate your company’s capabilities:

1. The data resource contains a minimum of 2 million currently continuously enrolled patients or covered lives within the United States of America as of July 1, 2013.

2. Demonstrated (post-HIPAA) ability to access and retrieve complete, integrated, laboratory, ambulatory and inpatient medical records linked to electronic pharmacy data for completion of studies with validated outcomes.

3. Demonstrated ability and experience in conducting:

a. Feasibility assessments

b. In-depth pharmacoepidemiologic drug safety studies

c. Evaluation of FDA risk communications management Programs

d. Methodological research for regulatory purposes

e. Theme-based drug safety Programs

4. Pharmacoepidemiologic expertise for scientific collaboration or consultative support.

Part B. Business Information

Please provide the following business information for your company/institution and for any teaming or joint venture partners:

• Company/Institute Name:

• Address:

• Point of Contact:

• CAGE Code:

• Phone Number:

• E-mail Address:

• Web Page URL:

• Size of business pursuant to North American Industry Classification System

(NAICS) Code: 541712 Size standard 500 Employees

Based on the above NAICS Code, state whether your company is:

• Small Business (Yes / No)

• Woman Owned Small Business (Yes / No)

• Small Disadvantaged Business (Yes / No)

• 8(a) Certified (Yes / No)

• HUBZone Certified (Yes / No)

• Veteran Owned Small Business (Yes / No)

• Service Disabled Veteran Small Business (Yes / No)

• Registered in System for Award Management (SAM). (Yes / No)

• College/University, or a Non-Profit Organization (Yes / No)

• A statement as to whether your company is domestically or foreign owned (if foreign, please indicate the country of ownership).

Part C. Estimated Dollar Range

What estimated dollar range would you determine this project to cost?