Clinical trials

Authorisation

What is the authorisation procedure for conducting clinical trials in your jurisdiction?

In the United States, the sponsor of a clinical trial involving a Food and Drug Administration (FDA)-regulated product must generally seek FDA authorisation for the research, unless specific exemption or risk-related criteria are met. For a pharmaceutical or biological drug, the sponsor submits an investigational new drug (IND) application, and for a significant risk device study the sponsor submits an investigational device exemption (IDE) application to the FDA. Research may begin 30 days after the FDA receives the application, unless the FDA advises the applicant otherwise, and provided that approval has also been obtained from an Investigational Review Board (IRB).  For non-significant risk device studies, the sponsor must comply with abbreviated IDE requirements and obtain IRB (but not FDA) approval to proceed. In some additional cases, even if an IND or IDE is not required because a study does not meet the triggering criteria under those regulations, the study may still be subject to IRB review and FDA informed consent requirements if the data will be submitted to or held for inspection by the FDA. Most research that is conducted or supported by federal government agencies or departments is also subject to the Common Rule, a set of human subject protection regulations that are similar but not identical to FDA rules. Steps have been taken towards harmonisation of these rules, but these efforts are still in progress. 

Clinical practices

How robust are the standard good clinical practices followed in your jurisdiction?

The requirements are quite robust. The FDA enforces good clinical practices for the conduct of clinical trials through regulations and draft guidance documents.

The following regulations govern the conduct of clinical trials:

  • 21 CFR § 11 (electronic records/signatures);
  • § 50 (protection of human subjects);
  • § 54 (financial disclosure);
  • § 56 (IRBs);
  • § 312 (Investigational New Drug); and
  • §§ 812 (Investigational Device Exemption).

FDA draft guidance on good clinical practices includes the types of informed consent term that constitute prohibited exculpatory language (see example) and expanded access to investigational drugs (see example).

The FDA has issued warning letters for violations of good clinical practices, including:

  • the failure to follow IRB procedures (see example);
  • deviations from the investigational plan (see example); and
  • failure to maintain adequate records (see example).

Reporting, disclosure and consent

What are the reporting and disclosure requirements for the results of clinical trials?

The responsible party must register an “applicable clinical trial” on ClinicalTrials.gov, as well as disclose certain types of information including:

  • a summary of clinical trial results;
  • updates on changes to the clinical trial; and
  • adverse event information.

The Department of Health and Human Services issued final implementing regulations governing the registration and disclosure requirements, and these requirements are codified in 42 CFR Part 11. For clinical trials funded by the National Institutes of Health (NIH), the responsible party must also comply with the NIH’s Policy on Dissemination of NIH-Funded Clinical Trial Information.

What are the informed consent obligations with respect to clinical trial subjects?

Investigators must obtain legally effective informed consent before involving subjects in a clinical trial, pursuant to 21 CFR § 50.20. The required elements of informed consent are outlined in Section 50.25, which serves to ensure that potential subjects make a voluntary and fully informed decision based on key study details such as the purpose of research, experimental procedures, foreseeable risks and benefits, and alternative courses of treatment, among other required disclosures. Informed consent must be documented in accordance with Section 50.27.

The FDA has issued warning letters for consent infirmities, such as:

  • failure to meet regulatory requirements (see example);
  • initiating testing prior to the date of consent (see example); and
  • not providing a copy of signed consent forms to subjects (see example).

Informed consent also must be obtained before screening and randomising subjects (see example).

Insurance

What are the insurance requirements for clinical trials?

There is no regulatory requirement that a sponsor of clinical trials in the United States purchase clinical trial liability insurance. However, such insurance is purchased to manage risks associated with patient injury. This includes potential defence and indemnification obligations that the sponsor may have to study sites, participating physicians, contract research organisations (CROs) and investigators. Insurance requirements are also part of the contracts that a sponsor will have with study sites, CROs and investigators, as well as with licensors and joint venture entities.

Clinical trial insurance can also be purchased in conjunction with product liability insurance to cover liability associated with product sales. Policies can cover multiple products across both approved and studied uses.

Data protection

What data protection issues should be considered when conducting clinical trials?

Depending on the circumstances and the types of information collected, a myriad of federal and state laws may govern data protection in the context of a clinical trial. At the federal level, for example, clinical trials conducted in the United States must conform to FDA regulations embodying good clinical practices and adequate human subject protection (HSP). HSP includes requirements to obtain informed consent from clinical trial participants (21 CFR Part 50); the informed consent must include a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the FDA may inspect the records. In addition, if the data is collected from a Health Insurance Portability and Accountability Act covered entity (which is typically the status of clinical study sites), each clinical trial participant must grant authorisation to disclose his or her protected health information (PHI) unless an exception is met (45 CFR § 164.502(a)). If certain requirements are satisfied, an Institutional Review Board or Privacy Board may waive, in whole or part, the authorisation requirement (45 CFR § 164.512(i)). Typically, the authorisation will include:

  • information regarding disclosure of PHI when it is required by law;
  • sharing of PHI to prevent or control injury or the spread of disease;
  • protection of patient identity in publications or public presentations regarding the trial; and prohibition on patient access to PHI before completion of the trial.

Additionally, 21 CFR Part 11 mandates standards for electronic records and systems to ensure accuracy, reliability and consistency of data. The Confidentiality of Alcohol and Drug Abuse Patient Records (CFR Title 42: Part 2) regulation also specifies restrictions concerning the disclosure and use of patient records that include information on substance use diagnoses or services.

To promote robust sharing of human and non-human data from a wide range of genomic research and to provide appropriate protections for research involving human data, the NIH issued the NIH Genomic Data Sharing Policy. The policy applies to all NIH-funded research (eg, grants, contracts and intramural research) that generates large-scale human or non-human genomic data, regardless of the funding level, as well as the use of this data for subsequent research.

Certificates of confidentiality, issued by the NIH, protect the privacy of research subjects by prohibiting disclosure of identifiable, sensitive research information to anyone not connected to the research except when the subject consents or in a few other specific situations. Certificates of confidentiality allow researchers to avoid being compelled to release research data in civil or criminal proceedings. They can be particularly helpful in protecting sensitive data that, if revealed, could lead to discrimination or reputational or other harm to research participants.

Specific issues that arise include notice and consent, secondary uses of data and specimen collection. Where there are sites outside the United States, many countries have data protection, health data or clinical trial laws that will impose different requirements in terms of transparency, consent and security.

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