NIH/NIDA – Laboratories for Early Clinical Evaluation of Pharmacotherapies for Substance Use Disorders (UG1 Clinical Trials Required)

January 10, 2019 by kjt5j@virginia.edu

The purpose of this Funding Opportunity Announcement (FOA) is to accelerate the clinical development of medications to treat Substance Use Disorders (SUDs) by establishing Laboratories with the expertise and resources to timely and efficiently conduct early (Phase 1 or Phase 2) clinical trials of potential pharmacotherapies for SUDs.

A significant challenge in the development of medications for SUDs is the need of specialized Laboratories that have the knowledge and expertise to timely and efficiently conduct FDA-defined Phase I and Phase II clinical trials. For example, Phase I clinical trials in addictions have to evaluate the medical safety of compounds and may involve the evaluation of safety of the interaction with a drug of abuse or pharmacokinetic or pharmacodynamic studies. Such studies require an inpatient unit where subjects can feel comfortable and have adequate medical monitoring and other safety protection measures in place. These studies will also require a pharmacy support with a set of licenses and permits to allow the storage and administration of some substances, for example DEA scheduled drugs.

Phase II studies mainly focus on the evaluation of the safety and early efficacy of medications. They can be conducted in outpatient settings, with treatment-seeking populations, and may have strict inclusion/exclusion criteria, as well as specific treatment outcomes.  The settings where Phase II studies are conducted must have personnel with the knowledge and expertise in the area of early clinical research, ability to recruit study participants, and clinical services to attend to the needs of patients participating in clinical trials. Also, they must possess the necessary licenses and certificates to conduct these types of trials and the ability to follow Good Clinical Practice (GCP) guidelines. The data collected from these studies must also satisfy the FDA quality requirements to support the approval of the medication.

Given the high level of specialization and strict regulatory requirements to conduct early clinical trials of medications for SUDs, it is critical to strengthen the capacity to execute and/or increase the availability of Laboratories able to perform high quality early studies in a cost-effective way. These Laboratories must have the ability to recruit participants with SUDs who are not seeking treatment. Moreover, they must be able to conduct GCP quality studies that satisfy the FDA requirements to accept the data for approval purposes.

It is expected that each laboratory will be able to provide leadership and technical expertise for the field and will be GCP-compliant. The Laboratories will have access to an Institutional Review Board (IRB) to perform timely and efficient review and oversight, are expected to possess a track record of success in key operational aspects of drug development, such as successful clinical study initiation and recruitment, demonstrated ability to complete clinical studies within standards and timelines comparable to the pharmaceutical industry.

Without being constrained by staying within the limits of one theme or indication (e.g., one SUD), the Laboratories can have a broad range of projects that could be independent or connected and executed simultaneously or overlap, or be sequential. The Laboratory can be a stand-alone site or have networked sites and Laboratories each with their own clinical studies capabilities and infrastructure.  Integration of data, resources and instruments across projects is allowed as well, based on where and if needed.

It is important to note that Phase I clinical trials in SUDs have to evaluate the medical safety of compounds and may involve the evaluation of safety of the interaction with a drug of abuse. Early phase trials can also include the following types of trials:

  • Early clinical studies with potential medication candidate, such as First time in Humans (FIH), Single Ascending Dose (SAD), Multiple Ascending Dose (MAD) or SAD-MAD combination, food effect
  • Drug-Drug interaction (DDI) studies, including safety interaction studies of medications with drugs of abuse.
  • Other studies related to aspects of formulation development (e.g. bioavailability)
  • Translational Phase 2A proof-of-mechanism (POM) studies. It is expected that neuroimaging and other technologies will be used where appropriate.
  • Phase 2B dose-ranging and/or Early Signal of Efficacy (ESoE) type of trials
  • Proof of Concept (POC) efficacy and safety clinical trials

This FOA aims to support clinical research Laboratories with the basic resources and services necessary to conduct early clinical trials. Each application must include one or two clinical trials that can be conducted in the first two years of the project and will serve to demonstrate the ability of the laboratory to conduct such trials.  The compounds to be tested in the clinical trial may be proposed/supplied by any academic, industry or government sponsor.   It is expected that each laboratory will participate in at least one clinical trial at a given time. Failure of a laboratory to participate in clinical trials may jeopardize future funding of the laboratory.

As the opportunity arises, requests for subsequent clinical trials can be submitted by the Principal Investigator (PI) as an administrative supplement request.

Special Considerations

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects:  The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects.   Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects.  The guidelines are available on NIDA’s Web site at  http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects.

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA’s credibility and reputation within the scientific community.  Please see http://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding- for details.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit:  NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org).  Please see NOT-DA-12-008 (http://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details.

Deadline:  March 15, 2019 (letters of intent due 30 days prior to deadline)

URL:  https://grants.nih.gov/grants/guide/rfa-files/RFA-DA-19-018.html

Filed Under: Funding Opportunities