Clinical trials must comply with many requirements that do not apply to other types of human subjects research. These requirements are designed to address the increased participant vulnerability and risks of many clinical trials compared with other research. They are also meant to ensure meaningful results.
A clinical trial is a research study that prospectively assigns one or more human subjects to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.
The term applicable clinical trial refers to specific types of studies that are required to comply with federal requirements about registration and results reporting of clinical trials at the website ClinicalTrials.gov.
NIH grant applications. It is essential to decide whether your planned research is a clinical trial, when preparing a grant or contract application for the National Institutes of Health (NIH). Clinical trial applications can be submitted only in response to specific Funding Opportunity Announcements. In addition, there is significant required grant content that is specific to clinical trials.
While NIH does use the definition provided above, the NIH interpretation of the definition is far broader than many investigators realize. HSD has prepared a one-page document with resources and advice to assist investigators with this important assessment.
The UW IRB does not review all UW clinical trials. Many different IRBs might review clinical trials conducted by UW. Review the information about different IRBs to identify the correct IRB.
Billing and costs for clinical study procedures
Clinical trials that will bill subjects’ health insurance, a study sponsor, or a grant for clinical services, items or tests that are provided by the following facilities must obtain a pre-award review from the UW’s Clinical Research Budget and Billing (CRBB): UW Physicians, Seattle Cancer Care Alliance or UW Medicine hospitals or clinics, including UW Medical Center, Harborview Medical Center, Eastside Specialty Center, Hall Health Primary Care Center and Sports Medicine Clinic. The review provides technical assistance, advice, tools and resources regarding third party payer reimbursement, budget development and billing, and Clinical Trials Policy (CTP) coverage analysis. This analysis will also identify any post-award responsibilities related to billing such as IRB fees.
Clinical trials registration and results reporting
Applicable clinical trials must be registered at the federal website called ClinicalTrials.gov. The registration record must be updated at least annually, and the trial results must be reported. HSD provides administrative support, guidance, and instructions.
Consent forms for clinical trials must comply with the following requirements:
- Clearly identify any costs that will be the subjects’ responsibility.
Examples: If health insurance will be charged for trial-related procedures and items, will subjects still be responsible for co-pays and deductibles? Is there clinical care that will occur at the same time as the research procedures but that are not part of the research – and for which subjects’ health insurance will be asked to pay?
- Consistency among consent form, Clinical Trial Agreement (contract), and CRBB-approved budget
For industry sponsored trials, the information about who will pay for which study procedures, and about injury compensation, must be consistent among these three documents.
- Billing federal health insurance programs (Medicare, Tricare)
There can be no language that suggests that Medicare, Tricare, or other federal health insurance programs will be charged and that the sponsor will pay whatever the insurance does not pay. This is a violation of federal law (Medicare Secondary Payer rule) and can result in a False Claims suit against the UW.
- Information about ClinicalTrials.gov registration
The consent form must include a specific statement about the ClinicalTrials.gov registration, if the trial is required to be registered. By regulation, the wording of the sentence cannot be changed. See the UW consent template.
Consent form repository
Federally-supported clinical trials that received initial IRB approval on or after January 21, 2019 must upload an unsigned copy of the study consent form to a publicly available federal website. See this webpage for details and instructions.
Data and Safety Monitoring Plan
A Data and Safety Monitoring Plan (DSMP) is required. Industry sponsors typically build these into the study protocol. For non-industry trials, the PI or trial management group is responsible for developing and implementing the DSMP. See the UW ITHS website for information, tools, and templates.
Emergency medicine clinical trials
Many emergency medicine trials occur in patient populations and settings for which it is not possible to obtain consent. If the trial involves more than minimal risk to the participants, then the IRB application must provide additional information, and the study must comply with many additional requirements. These significantly increase the time required to obtain IRB approval.
The Food and Drug Administration (FDA) regulations apply to many clinical trials involving drugs, devices, or biologics. These may require the academic researcher to submit an IND application (drugs, biologics) or IDE (device) application to the FDA before beginning the study. When approved, the IND or IDE application allows the investigator to obtain and use the drug, biologic or device for research purposes. See the ITHS website for guidance, tools, and templates for this time-consuming process.
Interpretation and translation
Federal non-discrimination laws must be considered when developing subject inclusion/exclusion criteria. Specifically, it is not acceptable to exclude possible subjects on the basis of age, gender, race, ethnicity, disability, or not speaking English (in a domestic study), unless there is a scientific rationale for doing so.
This means that researchers should develop a plan and budget for how translation and interpretation will be provided for interested and eligible subjects. For studies that are likely to have small numbers of these subjects, this is may be best handled by including in the budget the cost of retaining an interpretation and translation service that can be called upon as needed.
The principal investigator and other relevant members of the study team must fulfill training requirements before conducting a clinical trial that is funded by a federal agency and/or that is subject to FDA regulations. The requirements:
- One-time completion of training about human subjects research and protections
- Completion of Good Clinical Practice (GCP) training once, followed by a refresher every 3 years
The UW’s Institute for Translational Health Sciences can provide a wide variety of services and tools to assist with all aspects of a clinical trial. This includes regulatory coordinators and clinical study coordinators, available on an hourly or FTE contracted basis.