Updated: 6/9/2005

Purpose of this Guidance

1. Why is it important to develop a plan that identifies available sources of antiretroviral treatment for research participants in NIH-funded/supported antiretroviral treatment trials after their completion of the trial?

2. Why can't the NIH provide support for antiretroviral treatment following the completion of a trial?

3. What is meant by the participant's �completion of the trial�?

Types of NIH-Funded/Supported Clinical Trials Covered by this Guidance

4. How does the NIH define �HIV antiretroviral treatment trials� covered by this Guidance?

5. Why is this guidance limited to antiretroviral treatment trials?

6. Why does the Guidance apply only to trials being conducted in developing countries?

7. What definition does the NIH use for �Developing� Countries?

8. Does this Guidance apply to HIV antiretroviral treatment trials that have research sites in both the U.S. and in a developing country?

Identifying Sources and Developing a Plan

9. Does the recommendation that investigators work with �host countries' authorities� to identify sources for the provision of antiretroviral treatment mean that investigators can only interact with government entities in the host country?

10. What does the NIH mean by �identifying sources�?

11. Does the antiretroviral treatment identified for post-trial provision have to be the same regimen that the participant received during the trial?

12. Is there a standard format for plans that identify source(s) for the provision of antiretroviral treatment?

13. How should the documentation of the plan be provided?

14. When should the plan that identifies source(s) for the provision of antiretroviral treatment be submitted to the NIH?

15. What information needs to be included and evaluated in the plan?

16. What type of document is required if there are no sources for antiretroviral treatment in or available to a particular country?

17. Who is responsible for determining whether a plan that identifies sources for the provision of antiretroviral treatment following the completion of the study is sufficient and appropriate?

18. If the documentation provided indicates that, prior to award, the applicant cannot identify available sources for the provision of antiretroviral treatment following the completion of the trial because there are no available sources, does that mean that an application with a fundable score will not be funded or that an otherwise successful proposal will not be awarded a contract?

Purpose of this Guidance

It is important to develop a plan so that participants in developing countries who volunteer to participate in an HIV antiretroviral treatment trial have the option to continue to receive antiretroviral treatment following their completion of the trial. Without such a plan, there is an increased possibility that trial participants may not receive post-trial antiretroviral treatment. This would end the benefits of treatment they received during the trial and could affect their ability to use certain antiretrovirals in the future. Therefore, NIH-funded investigators, working with host countries' authorities and other stakeholders, are expected to identify sources available in the countries for the provision of antiretroviral treatment to trial participants following their completion of the trial.

The NIH is statutorily authorized to support and conduct biomedical research. 42 USC 284 (b) (MS Word - 30 KB). In the research arena, the NIH may not support or provide services beyond its statutory authority such as providing antiretroviral treatment following the completion of a trial. However, the NIH recognizes that it is important that individuals who volunteer to participate in NIH-supported/funded HIV antiretroviral treatment trials have the option to continue to receive antiretroviral treatment following the completion of the treatment trial.

For the purposes of this Guidance, �completion of the trial� is defined as when:

• A participant completes the trial schedule as outlined in the protocol;
• A participant follows the trial schedule until the trial is terminated prematurely by the Data Safety Monitoring Board, Ethical Review Committee, Institutional Review Board, or other official group; or
• A participant follows the trial schedule until the participant develops drug toxicity or failure.

Applicability of this Guidance to a participant who withdraws from a trial for reasons not listed above will be considered on a case-by-case basis.

Types of NIH-Funded/Supported Clinical Trials Covered by this Guidance

HIV antiretroviral treatment trials that are subject to the provisions outlined in this document are defined as clinical trials conducted in developing countries where antiretroviral medications are provided to enrolled subjects in order to assess the safety and efficacy of HIV antiretroviral treatment regimens.

Although there may be other situations where guidance is needed, the situation involving HIV antiretrovirals treatment trials creates the most critical scenario; this is the one addressed by this Guidance. Often in HIV antiretroviral treatment trials, a large number of people receive varying protocols of antiretroviral treatments for a long period of time. In many developing countries, individuals have difficulty obtaining antiretroviral treatment. Now that the NIH has increased its support of HIV antiretroviral treatment trials in developing countries, issues regarding post-trial treatment for individuals who participate in these trials must be addressed. Discontinuation of antiretroviral treatment when a trial ends could have negative health effects, which include the increased risk of mortality. To help prevent the possibility of such adverse effects, the NIH developed this Guidance.

The Guidance addresses inequities in resources available to participants in developed versus developing countries. For trials conducted domestically, there are existing programs (e.g., pharmaceutical company patient assistance/compassionate use programs, Ryan White CARE Act, Medicaid, private insurance coverage) that can help trial participants continue to receive antiretroviral treatment following their completion of an antiretroviral treatment trial. Participants in developing countries may not have the same types of programs available to them.

For purposes of this Guidance, �developing countries� are defined as the low- and middle-income economies, using World Bank classifications. The World Bank's main criterion for classifying economies is gross national income (GNI) per capita, calculated using the World Bank Atlas method. Classification by income does not necessarily reflect development status. The developing countries include: low income , $735 or less; lower middle income , $736 - $2,935; and upper middle income , $2,936 - $9,075.

See http://www.worldbank.org/data/countryclass/classgroups.htm for a list of the countries included in each group.

For HIV antiretroviral treatment trials conducted at research sites in both the U.S. and developing countries, the Guidance applies only for that part of the trial being conducted in a developing country. The Principal Investigator is encouraged, however, to include sources for the provision of antiretroviral treatment in the U.S. that are available to trial participants at the conclusion of their participation in the trial.

Identifying Sources and Developing a Plan

No. In addition to authorities in the host country (i.e., the local, state, or national government), other entities that should be engaged include non-governmental organizations/groups, non-profit organizations, foundations, etc. that are in, or operating in, the host country.

It is important that Principal Investigators work with local investigators to negotiate, plan, and explain early on to the �stakeholders� (e.g., communities from which participants are to be drawn, host countries' authorities, country scientific and ethics committees) how the issue of treating HIV antiretroviral treatment trial participants following their completion of the trial will be addressed. Plans corresponding to different scenarios may need to be entertained for both the provision of treatment and the entities that will provide treatment. A number of options for provision of treatment may be acceptable, as long as plans are disclosed as early as possible to all stakeholders. Some examples follow:

• For countries that receive funding for antiretroviral treatment from identifiable sources (e.g., the Global Fund to Fight AIDS, Tuberculosis and Malaria, the President's Emergency Plan for AIDS Relief), the investigator(s) could engage the recipient of the funding (i.e., the host countries' Ministry of Health) in discussion and receive acknowledgement of the need for the continuation of antiretroviral treatment for trial participants;
• For sites where there is an HIV clinic within a reasonable distance, the investigators could engage the director of the clinic in discussions to obtain agreement from the clinic to provide trial participants with antiretroviral treatment at the clinic following the trial;
• For countries with national programs that cover antiretroviral treatment, the investigator(s) could engage Ministries of Health in discussions and receive acknowledgment that, following their completion of the trial, participants will be able to receive antiretroviral treatment under the national program at a convenient health care facility;
• Other options specific to the country or other sources of funds to purchase/distribute antiretroviral treatment not included above.

No. The purpose of this Guidance is to assert the importance of trial participants being able to continue to receive effective antiretroviral treatment after the trial ends but not to specify a particular type of treatment. Treatment regimens should be determined based on individual medical needs, what is available in the host country, and progress in the field.

There is no standard �format� for plans. However, questions 15 and 16 outline the information that must be included in plans.

For grants and cooperative agreements, a letter or memo, from the Principal Investigator should be sent to the NIH Program Official, identifying sources and describing how those sources may be utilized at the completion of a trial. For contracts, this documentation should be submitted with the proposal solely to the Contracting Officer. The requirements and process for this will be included in the relevant PA/RFA/RFP or provided by the NIH Program Official/Project Officer.

• For grants and cooperative agreements, the plan should be provided at the time that NIH Just-In-Time information is submitted. Investigators should review their plan annually, and if any updates are needed, the revised plan should be submitted with their Non-Competing Grant Progress Report.
• For clinical trials networks (cooperative groups that initiate multiple trials over an award period) the plan should be provided prior to Institute(s)/Center(s) approval to initiate each trial.
• For contracts, the plan must be provided with the offerors' proposal, along with any other required Human Subjects information.

All plans submitted must include the following:

• Description of available sources, if any, (e.g., name of source, location, contact person of facility/organization) for the provision of antiretroviral treatment and care following the completion of the trial;
• Summary of the investigator's interaction with the providers;
• Documents, if any, from available sources/providers regarding plans for implementation;
• Description of how this information will be conveyed to the participants.

• Statement confirming that at the time of application no sources of antiretroviral treatment could be identified;
• Description of how this information will be conveyed to the trial participants;
• Brief description of avenues that were explored to identify sources;
• Commitment to continue to explore potential sources as the trial proceeds.

For grant applications and cooperative agreements, the documentation submitted will be evaluated by the NIH Institute/Center through the Program Official. If necessary, Program Staff will work with the applicant to ensure that the documentation is sufficient and appropriate.

For contracts, the documentation will be submitted to the Contracting Officer and evaluated by the Institute/Center Project Officer.

Not necessarily. The Guidance states that �priority may be given to sites where sources are identified for the provision of antiretroviral treatment following the completion of the trial;� however, this does not rule out NIH funding trials where sources have not been identified prior to award.

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