Navigating Duty-to-Warn Challenges in Biotech Clinical Trials

Biotechnology products in clinical development, such as gene therapies, cell therapies, and monoclonal antibodies, pose special liability challenges. These therapies operate on biological pathways that are far less predictable than traditional small molecule drugs. Several factors elevate the risk profile in biotech trials:

• Greater Scientific Uncertainty: Novel therapies often alter the body permanently (e.g., inserting genes) with little prior human data.

• Unpredictable Immune or Genetic Effects: Biotech interventions carry risks of off-target or unintended effects that are difficult to anticipate. Early gene transfer trials showed unexpected immune reactions, underscoring the difficulty of predicting safety. Regulators acknowledge that long-term exposure to an investigational gene therapy may put subjects at increased risk of undesirable and unpredictable outcomes that only manifest as delayed adverse events.¹  In practical terms, this means a participant might suffer a health problem years after the trial, due to the trial therapy.

• Long-Term Unknowns: Unlike a pill that leaves the body in hours, many biologics (e.g., gene-editing therapies or viral vector gene therapies) can persist for years or permanently integrate into a patient’s genome. This raises the specter of delayed harm, such as insertional mutagenesis (unintended genetic disruptions that could lead to cancer) or late-arising autoimmune disorders. The full safety profile may not be understood for decades. Sponsors must warn about categories of risk (like “possible unforeseen genetic damage” or “unknown long-term effects”) even if no such event has yet been observed. In effect, the duty to warn extends to reasonably foreseeable risks that are theoretical but plausible given the biology. In biotech trials, the duty to warn extends beyond known side effects to categories of plausible risks, making the ICF central to disclosure.

In traditional product liability law, manufacturers discharge their duty to warn by informing physicians (the “learned intermediaries”), who counsel patients. However, in clinical trials, that dynamic shifts. When human subjects are receiving an experimental biotech product, the sponsor cannot rely on the learned intermediary doctrine alone, the sponsor (along with investigators) must warn trial participants directly through the informed consent process. In fact, lawsuits by clinical trial participants frequently allege that the sponsor failed to properly warn them of risks via the consent form. Courts often treat the ICF as primary evidence of what participants were told.

Complicating matters further, the duty to warn in a trial is ongoing. It’s not a one-time check-the-box at enrollment. As the study progresses, new safety data may emerge — perhaps an unexpected serious adverse event in one of the participants or a new finding from a related study. Sponsors have a duty to update participants (and the consent form) with any new significant risk information discovered during the trial. Per the U.S. FDA’s “Final Guidance Document: Long Term Follow-up After Administration of Human Gene Therapy Products,” regulations explicitly require that if new adverse events are identified, the sponsor must revise the investigator brochure and informed consent documents and inform all investigators of the new risks . Failing to do so not only violate ethics and regulations but also opens the door to negligence claims. A sponsor cannot hide behind the fact that a risk was not known at trial start if by midway through the trial there were warning signs — at that point, the duty to warn compels disclosing that evolving risk to ongoing participants and perhaps re-consenting them.

The ICF is the linchpin of both ethics and liability defense. It is the document (and process) through which sponsors fulfill their duty to warn, and it can significantly mitigate liability if done properly. Sponsors are legally required to include certain key risk information in the ICF. The FDA’s regulations (21 CFR §50.25) mandate that each subject be provided “a description of any reasonably foreseeable risks or discomforts” of the research. In a biotechnology trial, this encompasses not only the side effects observed in preclinical testing or earlier phases, but also foreseeable risks inherent to the product’s biology. IRBs also insist on clear disclosure of investigational status and unknown long-term effects. Thus, the very structure of the ICF — as required by FDA and IRB guidelines — is designed to force sponsors to confront and disclose risks up front.

In high-uncertainty trials, a well-crafted ICF explicitly acknowledges what is not known as well as what is known. This honest disclosure of uncertainty is a critical risk mitigation strategy. Rather than assure participants of outcomes, the sponsor must clearly state, for instance, “Because this is a new gene therapy, there may be risks that researchers do not yet know. The treatment might have effects that are unexpected or that appear much later.” Regulators increasingly expect such language. FDA guidance on cell and gene therapy trials emphasizes that investigators should be open about what they do not know regarding risks and benefits.² By transparently conveying the limits of current knowledge, the ICF preempts accusations that the sponsor hid or minimized the unknown.

One of the strongest protections an ICF affords sponsors is the participant’s signed acknowledgement of the risks. In tort law, if an individual knowingly assumes a risk, it can limit the liability of the party who exposed them to that risk. The informed consent form, when properly executed, is tangible evidence that the participant assumed the risk of the trial’s known and potential hazards. While it does not waive negligence, it strengthens defenses against claims of nondisclosure. This documentation can undercut a plaintiff’s claim that “I was never warned this could happen.” This does not absolve a sponsor from conducting trials safely, but it is a critical component of the sponsor’s defense that the participant’s injury, if within the realm of disclosed risks, was a risk they agreed to take.

Crafting an effective informed consent form for a biotechnology trial requires special care. It must convey complex, high-stakes information in a manner that is understandable, comprehensive, and legally robust. Below are a few key best practices in drafting biotech ICFs that help maximize participant understanding while also mitigating sponsor risk:

• Use Plain Language: Translating scientific jargon into lay-friendly language is essential. Complex terms like “CRISPR off-target mutagenesis” should be explained in everyday language. A form that participants cannot understand undermines true informed consent and weakens its legal force.

• Explicitly Categorize and Detail Risks: Given the layered nature of risk in biotech, it’s helpful to organize the risk section of the ICF into categories: for instance, “Known Side Effects,” “Possible but Uncertain Risks,” and “Unknown/Unforeseeable Risks.” Then, include a catch-all statement that there may be risks that researchers do not yet know. By explicitly flagging each tier of risk, the consent form makes it clear that everything from common immediate side effects to remote unknown hazards has been considered and disclosed. Being exhaustive but organized in risk disclosures is key in biotech trials.

• Highlight Experimental Status: A common misconception among trial participants (fueled by hope or therapeutic optimism) is that the investigational product might directly benefit them. In reality, early-phase biotech trials are usually more about safety and dosing than guaranteed benefit. The consent form should clearly state that the product is not yet proven safe or effective and is not approved by the FDA for general use.

• Ensure Consistency Across Sites and Updates: Biotechnology trials are frequently multi-center, sometimes international. Each site’s IRB might suggest tweaks to the consent form. The sponsor must harmonize risk disclosures across all sites, so that every participant in the trial is warned equivalently. Inconsistencies can be a liability if, say, a plaintiff finds that another site’s consent mentioned a risk that their site’s consent omitted. Dynamic updating of the ICF during the trial is critical. When new information arises, the sponsor should promptly revise the consent form and get IRB approval for the updated language. Sponsors must keep track of version control: record who signed which version and ensure no one is enrolled under an outdated form that lacks critical risk data.

In drafting the above elements, the tone of the consent form should remain neutral, factual, and non-promotional. Any language that could be construed as minimizing risk or overstating benefit should be avoided.

The landscape of informed consent in clinical trials is not static. In recent years, regulators have been raising the bar for what constitutes adequate informed consent, especially as trials grow more complex. The FDA has updated its guidance to emphasize improving participant comprehension. Notably, in August 2023 the FDA issued a Final Guidance on Informed Consent which, among other things, encourages researchers to use innovative methods and technologies to communicate trial information. Regulators are also increasingly insisting on Key Information sections, which are concise summaryies of the most critical info at the front of the consent forms. All these trends signal that sponsors should be prepared for more intensive review of their consent forms by FDA and IRBs, with an eye toward truly informing the participant in a meaningful way, not just ticking legal boxes.

In the era of social media and empowered patients, informed consent documents are increasingly coming under the scrutiny of patient advocacy groups and trial participants themselves. A trend has emerged where patients and independent advocates actively review consent forms to push for simplification and transparency.³  For instance, in the cancer research community, patient advocates have been involved in initiatives to rewrite consent templates in more lay-friendly language, recognizing that overly complex forms deter enrollment and can exclude less-educated populations. The patient advocacy movement is effectively raising the standard for what is considered an acceptable consent form. The bottom line is that informed consent quality is becoming a marker of corporate responsibility in the eyes of the public.

Clinical trials of biotechnology products will always carry a degree of uncertainty and risk. The informed consent form is not a panacea for all liability. However, a well-executed informed consent process is one of the most effective risk management tools a sponsor has for navigating the duty-to-warn challenge.

Biotech sponsors should approach informed consent with the same rigor as any other critical trial component. This means investing the time to draft clear and complete consent documents, updating them as new data emerges, and ensuring participants truly understand what they are agreeing to. When done correctly, informed consent becomes a win–win: participants are better protected, and sponsors significantly reduce their legal exposure by fulfilling their duty to warn in a demonstrable way. The ICF transforms the abstract duty to warn into a concrete record of warnings given and accepted. By wielding the informed consent form as both an ethical covenant and a legal instrument, sponsors can more safely pursue innovation, knowing they have been transparent about the risks that accompany the rewards of cutting-edge biotechnology.

1. Long Term Follow-up After Administration of Human Gene Therapy ProductsGuidance for Industry. U.S. Food and Drug Administration. Jan. 2020.

2. “Informed Consent.” American Society of Cell + Gene Therapy. Accessed 23 Sep. 2025.

3. “Toward More Inclusive, Accessible Clinical Trial Consent Forms.” WCLC News. 15 Oct. 2021.