NIHAO200816amd3.pdf

PAGE OF PAGES AMENDMENT OF SOLICITATION / MODIFICATION OF

CONTRACT

1. CONTRACT ID CODE

1 1

2. AMENDMENT/MODIFICATION NO.

3. EFFECTIVE DATE

August 27, 2008

4. REQUISITION/PURCHASE REQ. NO

5. PROJECT NO.

(If applicable)

6. ISSUED BY

National Institutes of Health, NIAID, AMOB

CODE

7. ADMINISTERED BY

10401 Fernwood Road, MSC 4813 Bethesda, MD 20817

9A. AMENDMENT OF SOLICITATION NO.

NIHAO200816

9B. DATED (SEE ITEM 11)

July 25, 2008

10A. MODIFICATION OF CONTRACT/ORDER NO.

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP code)

FACILITY CODE

10B. DATED (SEE ITEM 13)

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers is extended is not extended.

Offerors must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended, by one of the following methods: (a) By completing Items 8 and 15, and returning 1 copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted; or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGEMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

12. ACCOUNTING AND APPROPRIATION DATA (If required)

13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS

IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify Authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT ORDER NO. IN ITEM 10A.

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation data, etc.) SET

FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY

C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority)

E. IMPORTANT: Contractor is not, is required to sign this document and return copy to the issuing office.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible)

This amendment hereby revises Appendix C to the statement of work to be consistent with guidance provided via the responses to questions. Offerors are instructed to disregard the response to question #8 included in Responses to Questions #4. A revised copy of Appendix C is attached to this amendment.

The hour and date specified for receipt of Offers is hereby extended. Proposals for furnishing the supplies and/or services in THE SCHEDULE will be received at the place specified in, and in the number of copies specified in Attachment 1, "Packaging and Delivery of the Proposal," until 2:00 p.m. local time on 9/2/08. Offers will be valid for 120 days unless a different period is specified by the offeror on the Attachment entitled, "Proposal Summary and Data Record, NIH 2043.

ALL OTHER TERMS AND CONDITIONS OF THE SOLICITATION REMAIN UNCHANGED AND IN FULL

FORCE AND EFFECT.

Except as provided herein, all terms and conditions of the document referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in full force and effect.

15A. NAME AND TITLE OF SIGNER (Type or print)

16A NAME AND TITLE OF CONTRACTING OFFICER (Type or print)

Terrie Nestor, Contracting Officer

15B. CONTRACTOR/OFFEROR

(Signature of person authorized to sign)

15C. DATE SIGNED

16B. UNITED STATES OF AMERICA

(Signature of person authorized to sign)

16C. DATE SIGNED

NSN 7540-01-152-8070

PREVIOUS EDITION UNUSABLE

30-105

STANDARD FORM 30 (Rev. 10-83) Prescribed by GSA

FAR (48 CFR) 53.243

APPENDIX C: SAMPLE STUDY REQUIRING ADMINISTRATIVE & MANAGEMENT SUPPORT

SERVICES

NIAID‐Mali HIV Research Initiative

TABLE OF CONTENTS

1. INTRODUCTION 3

1.1 SUMMARY 3

1.2 NEED 4

1.3 OPPORTUNITY 5

1.4 CHALLENGE 6

1.5 RESPONSE 7

SAMPLE STUDY REQUIRING ADMINISTRATIVE & MANAGEMENT SUPPORT SERVICES

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1. Introduction

1.1 Summary

In 1989, NIAID established a cooperative malaria research program with investigators at the Université du Mali, in the capital city of Bamako. This program has become a successful model for the development of other joint research programs in the developing world. We propose to establish a research initiative investigating the effects of HIV and its treatment in West African populations. In the initial stage, we will establish laboratory facilities, train personnel and conduct a well-defined pilot project. In the second stage, we will implement small-scale clinical trials. In the third stage, we will facilitate multiple trials conducted by both NIH intramural and extramural investigators.

All stages will require the close cooperation and participation of investigators at the

Université du Mali. Our overall goal is to help establish research infrastructure that facilitates research relevant to the African HIV epidemic, a necessary step to advance the global fight against AIDS.

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2001 Global Burden of HIV Infection 40 million People Living with HIV Worldwide

1.2 Need

After more than 20 years, the global HIV epidemic only grows in complexity. The developing world, and Africa in particular, bears the brunt of this epidemic. Nearly three-quarters of all people infected with HIV worldwide live in Africa. Because Africa and the developing world disproportionately bear this burden, the battle against HIV must ultimately be waged and won there. Because these countries have few resources, they require outside assistance to develop resources and strategies relevant to their local conditions. While existing strategies from the developed world can be adapted, many are not relevant. More local research is needed.

We propose both basic and applied research to address needs in the developing world. For example, tuberculosis is a frequent and devastating opportunistic infection in developing countries. Little knowledge exists explaining how HIV and tuberculosis negatively interact in humans. Basic research is needed. Once obtained, the knowledge gained from such research can then be applied to develop new drugs, vaccines and assays that address the tragedy of HIV and tuberculosis coinfection.

Of course, many anti-HIV resources already exist. But specific knowledge about how best to apply them in the developing world is lacking. For example, outcome studies performed in the developed world have been used to establish HIV treatment guidelines.

Included are strategies using immunology and virology parameters to decide when or when not to treat HIV infection. It is unclear if these guidelines are relevant in the developing world. One reason for the uncertainty is that people in the developing world encounter many more infections of all types, causing differences in their immune systems

(and immunology parameters) even in the absence of HIV infection. Therefore, applied research addressing treatment strategies appropriate to the developing world is needed.

Western Europe 560 000560 000

North Africa & Middle East

440 000440 000 Sub-Saharan

Africa 28 100 00028 100 000

Eastern Europe & Central Asia 1 000 0001 000 000

South & South-East Asia

6 100 0006 100 000 Australia & New Zealand

15 00015 000

North America 940 000940 000

Caribbean 420 000420 000

Latin America 1 400 0001 400 000

East Asia & Pacific 1 000 0001 000 000

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1.3 Opportunity

Mali is a stable democracy. The first democratically elected government came to power in 1992 and was reelected in 1997. On June 8, 2002, Amadou Toumani Toure became the newly elected President in the first peaceful transition of power between rival political parties. In a time of great political unrest in other parts of Africa, the stability and nonviolence of Mali are highly desirable characteristics that lend themselves to establishing a successful, meaningful, and long-lasting HIV research program in Africa.

CDC estimates that the prevalence of HIV-infection in Mali is between 2-4%, reaching 40% in high-risk groups. Opportunistic infections in Mali include pulmonary and extra pulmonary tuberculosis, toxoplasmosis, diarrhea diseases and cryptococcal infections. In addition, frequently encountered infections not routinely considered opportunistic infections include malaria, onchocerciasis and schistosomiasis. Thus, the spectrum of HIV disease and its coinfections in Mali is similar to that of all of Africa but in a setting not yet overwhelmed by HIV disease. In addition, few other HIV biomedical research efforts exist in Mali, creating an opportunity to meet basic and applied research needs in Mali and in Africa that are not being met by others.

The Dean of the faculté de médecine de pharmacie et d’odonto-stomatologie

(FMPOS) at the Université du Mali has expressed great interest in attracting HIV biomedical research to that country. He has identified a team of individuals interested in pursuing an HIV research agenda. Existing building space is available for laboratory and research support facilities. The university hospital, Hopital Point G, treats most Malians hospitalized with HIV complications. Infectious diseases physicians treating HIV patients have been trained in France. They are familiar with up-to-date European HIV treatment guidelines.

Since 1989, researchers from the Laboratory of Parasitic Diseases (LPD) in NIAID have collaborated with other researchers investigating malarial diseases in West Africa.

The Malaria Research and Training Center

(MRTC) is supported by NIAID's DIR, the

USAID, NIAID's Division of Microbiology and

Infectious Diseases (DMID), the NIH Fogarty

International Center and the World Health

Organization. The MRTC works in close cooperation with their Malian colleagues at the Université du Mali, located in the capital city of Bamako.

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The Malian government is committed to addressing the HIV epidemic in Mali.

They have drawn up a national plan of action, including treatment guidelines. It is likely that an application will be made to the Global Fund to begin more widespread HIV treatment efforts. In short, while Mali is an extremely poor country, many of the important components required to conduct effective HIV research are already in place.

Finally, the importance of the long-standing presence of the MRTC and NIAID collaborators in Mali cannot be overstated. The experience of NIH personnel serving as consultants, the existing NIH infrastructure and the excellent relationships with the university all provide an unprecedented opportunity to establish an HIV research program in Mali in a time-frame and at a cost that would be unimaginable elsewhere.

1.4 Challenge

Mali is a poor country and Africa is far removed from North America. For a successful NIAID HIV research initiative in Mali, onsite NIH personnel would help facilitate accountability, communication and continuity. Identifying and recruiting qualified individuals to live or travel frequently to Mali will be a significant challenge.

An effective HIV research program in the developing world requires state-of-the-art facilities. While some existing NIH infrastructure can be shared with the MRTC, most needs to be established. As yet, no adequate research laboratory space exists, and clinical laboratory facilities at Hopital Point G are inadequate to conduct HIV clinical trials.

Close cooperation and participation of local investigators is critical to the success of any clinical research project. Potential collaborators do not yet have the training or experience necessary to conduct HIV laboratory or clinical trials research. An additional challenge is that while fluent French is common, fluent English is unusual.

Finally, as with all clinical research projects, this project’s focus is on patients. In

Mali, most are extremely poor. Nearly half are illiterate. Virtually none speak English.

Drugs and health care considered standard in the United States are inaccessible. Studying such a patient population poses many unique problems and challenges.

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1.5 Response

We propose a 3-stage plan to respond to the HIV epidemic—a plan responsive to needs in Mali and Africa and capable of taking advantage of existing opportunities while overcoming unique challenges. While each stage will have different research objectives, all will have similar requirements: physical infrastructure, training, language skills and creation of funding mechanisms.

In the first stage, we will conduct a highly focused research project, capable of rapid initiation with limited patient enrollment, personnel and laboratory facility requirements. This protocol has been identified. It is designed to investigate the effects of tuberculosis treatment in the setting of HIV coinfection. Laboratory facilities will be renovated and equipped, for this and for future projects. NIH personnel will travel to Mali to provide training and Malian personnel will travel to NIH for additional training. Some

NIH personnel and contractors will be posted in Mali. The project is anticipated to begin in 2008 with completion by 2012. 200 patients will be enrolled over 24 months for a 52-week observation period.

In the second stage, we will initiate small clinical trials. Such studies will begin to address the applicability of existing treatment strategies to HIV-infected African populations. For example, they may include pharmacokinetic and pharmacodynamic studies. Time and resource efficiencies will arise because patients will be eligible to be enrolled in more than one study at the same time, including the initial pilot study. This minimizes duplications in cost, personnel and equipment. This project is anticipated to begin in the fall of 2008. Any additional training requirements will be met. 200 patients will be enrolled in this stage.

The final stage of the research initiative will accommodate multiple research projects conducted concurrently, funded either from NIH intramural, extramural or non-

NIH sources. This stage will accommodate both laboratory-based and clinical trials research. One of the main goals of this project is to establish research infrastructure. This infrastructure will help leverage new funding opportunities for research conducted in

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Africa that is relevant to Africa. Such research is necessary to advance the global fight against HIV. 200 patients will be enrolled in this stage.