FDA issued a draft guidance, Demonstrating Substantial Evidence of Effectiveness for Human Drugs and Biological Products (Draft Guidance), on December 19, 2019, as an expansion of its 1998 guidance, Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products (1998 Guidance). The 1998 Guidance provided examples of evidence that FDA could consider to be confirmatory evidence to potentially support FDA approval of a marketing application based on one adequate and well-controlled clinical trial. The new Draft Guidance provides further detail on clinical trial design considerations, as well as forms of confirmatory evidence that sponsors may consider when proposing to rely on a single adequate and well-controlled clinical trial.
After several delays, the revised US Federal Policy for the Protection of Human Subjects (also known as the Common Rule) went into effect on January 21. The Common Rule is generally applicable to research conducted or supported by one of the federal departments or agencies that has integrated the rule into its own regulations (e.g., US Department of Health and Human Services (including the National Institutes of Health), US Department of Agriculture, US Department of Defense). Some clinical trial sites may also apply the Common Rule across all clinical research projects, regardless of funding source, through a US Office for Human Research Protections Federal Wide Assurance.
Despite the mandate under the 21st Century Cures Act to harmonize FDA regulations with the Common Rule to the extent practicable and allowable under existing legislative provisions, FDA has yet to propose aligning regulations. Rather, FDA issued guidance titled Impact of Certain Provisions of the Revised Common Rule on FDA-Regulated Clinical Investigations. As of right now, while FDA is aware of new inconsistencies between its human subject regulations and the revised Common Rule, the agency has advised that when a given study is subject to both sets of regulations, the rule that offers greater human subject protection should be applied. The guidance sets forth FDA’s position on the following areas of potential discrepancies between the Common Rule and FDA regulations:
In the wake of several high-profile incidents regarding data privacy and the misuse of genetic and personal information, including the case of a Chinese scientist who attracted worldwide criticism after reportedly creating the world’s first human babies whose DNA is genetically modified, the Chinese government has recently issued several top-level policy directives reaffirming its commitment to strengthening cybersecurity and the protection of personal data and human genetic information and material. Though driven by recent events, these policy directives are intended to build upon and further strengthen already existing protections enshrined in the country’s constitution and Tort Liability Law, a process that had already begun with the passage of the country’s Cybersecurity Law (CSL) and General Principles of Civil Law in recent years. Specifically, the recent policy directives place strict prohibitions on the unauthorized use of human genetic material for research purposes and create administrative penalties for the unlawful cross-border transfer of genetic information, while simultaneously streamlining the regulatory approval process for such transfers in an effort to mitigate the impact of increased regulation on international cooperation within the life sciences industry.
FDA recently released the framework for its Real World Evidence (RWE) program, educating stakeholders about the agency’s approach to RWE when making efficacy decisions. The document is notable more for its discussion of the limitations rather than the potential for RWE. Although FDA plans to issue a number of RWE guidance documents and conduct RWE stakeholder events, the path to routine use of RWE looks to be a long and winding one.
Crucial to understanding FDA’s RWE approach is understanding the distinction between Real World Data (RWD) (e.g., data on patient health status and/or delivery of routine healthcare from a variety of sources) and RWE (e.g., clinical evidence on the use and potential benefits/risks of medical products derived from RWD). FDA intends to limit RWE use to supplemental indications and label changes for approved drugs/biologics (e.g., adding/modifying indications, changing dose/dosing regimens and routes of administration, adding new patient populations, adding comparative effectiveness/safety information). Moreover, while the life sciences industry tends to see the opportunities from RWD (e.g., electronic health record, medical claims/patient billing, patient/disease registry, and mobile device data), FDA primarily sees this information as an RWE source. This is not to say, however, that RWD is without use, as FDA plans to allow its use to improve study efficiency.
FDA recently announced a proposal to add an exception to the agency’s informed consent requirements. Under the proposed rule, FDA will allow Institutional Review Boards (IRBs) to waive or alter informed consent for clinical trials that present only minimal risk to the subjects. This proposal is similar to the policy set forth in FDA’s guidance document on the same topic, which we have written on previously.
As precision medicine gains momentum and in vitro diagnostics (IVDs) become increasingly used in clinical trials, pharmaceutical and biotechnology companies must quickly become familiar with the FDA’s investigational device framework. Based on concerns that drug clinical trial sponsors do not appreciate the need to follow device regulations when using “investigational” IVDs in clinical trials, in its draft guidance, FDA provides more structure around the incorporation of IVDs into clinical trials, and sets out its expectations about sponsors’ scope of review of the risk of use of such IVDs. The draft guidance will need to be factored into how pharmaceutical and biotechnology clinical trial sponsors use IVDs in clinical trials and work with device partners.