STATEMENT_OF_WORK_FY_2015_Allama_BZ_1.docx

STATEMENT OF WORK FY 2015-2016

Enrollment and Ascertainment of Families in Pakistan for Both Hereditary Hearing and Speech Disorders.

SCOPE

Under this task order, the contractor will find and enroll families from Pakistan, under the supervision of Dr. Sheikh Riazuddin, exhibiting either hereditary hearing impairment or stuttering into the two protocols that have been approved by the NIH IRB for these two purposes-- (1) “Nonsyndromic hereditary hearing impairment-gene mapping" OH93-DC-016, and (2) “Genetic Studies of Stuttering”, 97-DC-0057. Once enrolled, the contractor will perform clinical evaluations, collect DNA, and ascertain the families. The contractor will then send DNA samples, consent forms, and clinical data from the families to the LMG for further studies. This is done in order to satisfy the overall operational objectives of the Laboratory of Molecular Genetics (LMG). The primary objective is to identify mutations in genes and understand their pathology

ORGANIZATION

Laboratory of Molecular Genetics (LMG) National Institute of Deafness and Other Communication Disorders (NIDCD) National Institutes of Health (NIH) 35A Convent Drive (Porter Neuroscience Research Center II ) Bethesda, MD 20892 Dr. Thomas B. Friedman, Ph.D - Chief, Laboratory of Molecular Genetics, 1F-141 Dr. Dennis Drayna, Ph.D -Chief, Laboratory of Communication Disorders, 1F-127

MISSION:

This contract is intended to fund several aspects of our continuing collaborative studies on nonsyndromic hereditary hearing impairment and speech disorders, particularly stuttering, being carried out with studies of families in Pakistan. Continued clinical evaluation of the families needs to be performed. Continued enrollment of new families needs to occur. The NIDCD has maintained a longstanding collaboration in Pakistan to study the genetics of hearing and speech disorders. Researchers in the Laboratory of Molecular Genetics (Thomas B. Friedman, PhD and the Laboratory of Communication Disorders (Dennis Drayna, PhD) work with Professor S. Riazuddin’s Laboratory for Research in Genetic Diseases, previously at the National Centre of Excellence in Molecular Biology (NCEMB) and presently at the Allama Iqbal Medical Research Centre (AIMRC). Dr. Riazuddin serves as the Higher Education Commission National Distinguished Professor/Principal Investigator in these studies. This collaboration involves ascertaining families in Pakistan with hearing and speech disorders, and mapping the underlying genes for these disorders. Dr. Friedman is the PI for the hereditary deafness protocol and Dr. Drayna is PI on the stuttering protocol. Dr. Andrew Griffith, MD, PhD is the Medical Advisory Investigator on both protocols. DNA samples from all families that are enrolled in this study will be sent to the Laboratory of Molecular Genetics and the Laboratory of Communication Disorders for analysis along with a copy of the signed Informed Consent and clinical data for each participant. These samples have proven invaluable for the identification of mutations in the genes causing hereditary hearing impairment and in the genes causing stuttering.

BACKGROUND INFORMATION:

DNA samples from several hundred extended families have already been collected for these protocols under previous professional service contracts (PSC’s) with Professor Riazuddin. Professor Riazuddin’s laboratory, in Lahore, is the premier research facility for research on human genetic diseases in Pakistan. He has established collaborations with many laboratories in Europe, the US and elsewhere. Most notable of these endeavors in addition to those at the NIH are collaborations with Richard J. Roberts previously at Cold Spring Harbor Labs; Lawrence Loeb and Eugene Nester at University of Washington, Seattle, Marc Van Montagu at Ghent University, Belgium, Hans van Bookhoven at Radbound University Nijmegen Medical Centre, Netherlands and Robert H. Ropers at Max Plank Institute, Berlin, Germany. These collaborations are built on the strengths of participating laboratories designed to advance common goals. The US National Science Foundation (International Program), the Rockefeller Foundation and the National Research Council have also funded some of these USA-Pakistan collaborations. Dr. Riazuddin’s laboratory is funded by the Pakistani federal government, and works at the frontiers of molecular biological research. It is advised by the following Foreign Scientists Advisory Council

Dr. Roger McMacken E.V. McCollum Professor & Chairman Department of Biochemistry & Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, U.S.A.

Dr. R.J. Roberts (Nobel Laureate) Director of Research, New England Biolabs. Inc., Beverly, MA 01915-5510, U.S.A.

Marc Van Montagu, Institute Plant Biotechnology for Developing Countries, Department Molecular Genetics, Ghent University, K.L. Ledeganchstraat 35, B-9000 Gent, Belgium.

Dr. Eugene Nester, Department of Microbiology and Immunology, University of Washington Mail Stop SC-42, Seattle Seattle, WA 98195, U.S.A.

Dr. Lawrence A. Loeb, Director, Joseph Cottstein Memorial Cancer Res. Lab.

K-Block, Health Sciences Building, University of Washington Seattle, WA 98195, U.S.A.

Prof. Jeongbin Yim, Department of Biochemistry, Seoul National University, Seoul, S.Korea.

Prof. Ken-ichi Arai, Professor Emeritus, Tokyo University, Tokyo, Japan

In supporting these collaborative activities, this contract will benefit from the presence of a long established and highly respected research laboratory in a region of the world where many families practice consanguinity. Personnel from Dr. Riazuddin’s research laboratory will be encouraged to follow a long standing tradition of coming to the NIH for training as part of the collaboration established with Pakistan according to the guidelines sanctioned by our IRB, OPRR and the Division of International Services, NIH Fogarty Center. Historically, Drs. Drayna and Friedman have hosted numerous Pakistani trainees in our laboratories, and have a long history of successfully training Pakistani human geneticists and molecular biologists.

TASKS/ SERVICES-- The contractor shall:

1) Obtain Informed Consent and enroll additional volunteers from families with hearing loss, stuttering, and other speech disorders under a protocol approved by an Institutional Review Board (IRB) with a Federal-Wide Assurance (FWA) number. Dr. Riazuddin’s institution in Lahore, Pakistan maintains such a protocol, approved by their local IRB under FWA #00001758. Such families have proven essential in mapping and identifying novel deafness and speech disorder loci. This aspect of the contract involves many hours of travel to remote areas of Pakistan.

2) As needed, obtain audiograms, recorded speech samples, and associated clinical data for subjects currently enrolled in the projects.

3) Send copies of detailed clinical reports to the Laboratory of Molecular Genetics. In some instances extensive clinical testing is required as we attempt to better understand possible clinical manifestations of a particular mutation in organs other than those involved in hearing and speech.

4) Enroll families segregating hereditary deafness not due to mutations of reported DFNB genes and reported Usher syndrome genes. Performance for this aspect of the project will include obtaining informed consent, audiograms, electroretinogram, family histories and genealogies. Copies of consents, and other pertinent information along with DNA or blood or mouth swabs will be sent to the Laboratories of Molecular Genetics and Communication Disorders along with an initial analysis of genotypes for known loci associated with deafness. Enroll families exhibiting speech disorders. Studies of speech disorders will focus on stuttering and SLI. Work will consist of obtaining blood/DNA samples and clinical speech evaluations and histories from the members of large families segregating these disorders. Work will include additional individuals from previously sampled families, as well as ascertainment and sampling from new families that may arise in the course of the contract period

5) Continue to provide information on carrier status on the deafness family members enrolled in this study. DNA samples from the enrolled families segregating will continue to allow the Laboratory of Molecular Genetics, NIDCD to refine loci and identify genes responsible for inherited deafness. The LMG is a CLIA approved facility. DNA samples from the enrolled families segregating stuttering will continue to allow the Laboratory of Communication Disorders (LCD) to refine loci and identify genes responsible for inherited stuttering.

QUALITY ASSURANCE

The contractor must develop its own Quality Assurance Plan (QASP) as part of its proposal for a performance-based effort. The contractor’s QASP must be meet the minimum criteria established below. The contractor must strive to meet past performance levels that were acceptable and improve on those that were less than optimal.

CERTIFICATIONS, LICENSE, PHYSICAL REQUIREMENTS OR OTHER EXPERTISE REQUIRED.

The contractor must:

· Be cleared to work directly with Professor S. Riazuddin’s Laboratory for Research in Genetic Diseases, previously at the National Centre of Excellence in Molecular Biology (NCEMB) and presently at the Allama Iqbal Medical Research Centre (AIMRC).

· Be listed directly on both NIH IRB protocols-- OH93-DC-016 and 97-DC-0057, and on Dr. Riazuddin’s human subject’s research protocol.

· Have access to researchers and clinicians specially trained to perform ascertainment of the families, including fluent communication skills in both Urdu and Punjabi, an understanding of Pakistani culture, and familiarity with both rural and urban areas in Pakistan. Native Urdu and Punjabi speakers are preferred.

· Have access to clinicians trained and cleared to perform blood draws, hearing tests, balance tests and speech tests on families participating in the studies. Also have access to clinicians trained and cleared to perform general medical examinations of the participants and special eye and ear exams.

· Have access to geneticists who are trained and certified to construct pedigrees and obtain medical histories relevant to the studies for each family.

· Have access to researchers and students who are trained to perform DNA extractions from human blood and buccal swabs, perform quality checks on DNA samples, catalog/label DNA samples, and ship DNA samples to the NIH.

· Have access to researchers and clinicians who are trained in the legal requirements for working with human subjects, especially the requirements for obtaining and maintaining informed consents.

· Have access to all case histories, completed informed consents, samples and scientific data obtained from previously enrolled families in both the deafness and stuttering protocols.

· Must be familiar with Material Transfer Agreements involving both human and non-human research samples.

· Must have access to researchers and students who are trained to do both genotyping and sequencing experiments.

· Must have the ability and resources to send personnel from Dr. Riazuddin’s research laboratory to the NIH for training as part of the collaboration established with Pakistan according to the guidelines sanctioned by our IRB, OPRR and the Division of International Services, NIH Fogarty Center when necessary.

PERIOD OF PERFORMANCE

Performance period is June 15, 2015 – June 14, 2016.

PLACE OF PERFORMANCE

Allama Iqbal Medical Research Centre (AIMRC) in Lahore, Pakistan.

OPERATIONAL HOURS

Contractor’s working hours.

SAFETY ISSUES

The contractor is required to adhere to all rules and regulations pertaining to safety in its geographic location.

GOVERNMENT- FURNISHED EQUIPMENT, BADGE, KEYS AND/OR FACILITIES PROVIDED.

The LMG will provide the contractor with permanently barcoded tubes to put DNA samples into. Barcoded tubes are a requirement for all human specimens at the NIH. Should any personnel come to the NIH for training, they will be provided with an ID badge, keys, computer with accessories, cubicle, desk, and chair. They will also be provided with any necessary office and lab supplies necessary to complete their experiments, give presentations of the data obtained, and write papers.

BASIS FOR AWARD

The government intends to award on a best-value basis, using the Lowest-Priced Technically Acceptable (LPTA). An offeror who passes all of the technical criteria, and has acceptable past performance, will be available for award. At that point, the lowest priced offeror would be awarded the contract.

1. Technical Criteria

The minimum technical standards for this maintenance contract are listed below. Each one will be evaluated on a pass/fail basis. Failure to demonstrate within the offeror’s proposal that there is capability to meet the standard will result in a failing grade for that criterion. Failure in one criterion below will lead the offeror to be considered technically unacceptable, and will make the offeror unavailable for award. The contractor must be able to fulfil all (A-H) of these requirements.

A. Must fulfill all of the requirements listed as bullet points in the “Certifications, License, Physical Requirements or Other Expertise Required” section of this document.

B. Obtain Informed Consent and enroll additional volunteers from families with hearing loss, stuttering, and other speech disorders under a protocol approved by an Institutional Review Board (IRB) with a Federal-Wide Assurance (FWA) number. The protocol must be kept up to date.

C. Must comply with regulations regarding the confidentiality of the identities and diagnoses of research subjects enrolled.

D. As needed, obtain audiograms, recorded speech samples, and associated clinical data for subjects currently enrolled in the projects.

E. Send copies of detailed clinical reports to the Laboratory of Molecular Genetics and the Laboratory of Communication Disorders.

F. Enroll families segregating hereditary deafness and exhibiting speech disorders.

G. Obtain blood/DNA samples and clinical speech evaluations and histories from the members of large families segregating both hearing and speech disorders. Work will include additional individuals from previously sampled families, as well as ascertainment and sampling from new families that may arise in the course of the contract period.

H. Continue to provide information on carrier status on the deafness family members enrolled in both studies.

2. Past performance

Past performance is a major factor in determining how well the contractor will perform in the current period of time—if a contractor failed in the past on any of the below criteria, it is assumed that it will do so again. Likewise, if a contractor was able to meet the criteria below in the past, it is assumed that it will do so again. Past performance is the most important evaluation criteria. Past performance criteria include:

A. Must have complied with regulations regarding the confidentiality of the identities and diagnoses of research subjects enrolled.

B. Must have kept all human subjects protocols current and up to date.

C. DNA samples must have been correctly labeled on the tubes and the names corresponded correctly to the accompanying pedigree 95% of the time.

D. DNA samples must have had no contaminants or evaporation 95% of the time.

E. Informed consents must have been completed for all DNA samples sent, with correct signatures for adult participants, parent or guardian signatures for participants who are minors, signatures of witnesses, and signatures of research staff and clinicians involved in collecting the samples, 95% of the time.

F. Informed consents must have also had the family number and participant’s name written in English, 95% of the time.

G. Audiograms and recorded speech samples must have been correct and legible 95% of the time.

H. SLINK pedigree analysis results must have been correct 95% of the time.

I. The contractor must have corrected any incorrect information, clarified any vague or illegible information, and provided any missing information within a few weeks of being contacted by NIH

The customer has the right to inquire about past performance of a contractor with other customers who used that contractor in the past. The contractor shall submit references for past performance.

3. Price

Among those technically acceptable offerors that have acceptable past performance, the offeror with the lowest price will receive award.