Landscape of informed consent practices and challenges in point‐of‐care clinical trials

Abstract

Point‐of‐care trials, an approach to trial design that assesses medical product effectiveness while fully integrating research and care, represent a promising opportunity to generate practically relevant evidence efficiently for priority disease areas. However, this approach presents unique considerations for appropriate and ethical informed consent. As point‐of‐care trials evolve, it will be important to examine informed consent through the lens of their supporting technology, of the clinicians who are responsible for administering it, and of their broader regulatory environment. Steps should be taken to establish ethical standards for point‐of‐care trials that reflect and serve the best interests of patients while reducing administrative burden and complexity. Our commentary describes, overall and through the use of real‐world examples, how this work is vital to ensuring a modern clinical trial enterprise that is patient‐centered and equips patients to make fully informed decisions about their health care.

1. BACKGROUND

COVID‐19 highlighted the need for more rapid, affordable, and practical evidence generation to support medical product development, regulatory review, and clinical implementation. ¹ , ² Point‐of‐care trial approaches to conducting pharmacoepidemiology research and prospectively generating real‐world data and real‐world evidence have recently become a potential approach to address this need. ³ , ⁴ , ⁵ Notably, point‐of‐care trials leverage electronic health records (EHR) and supporting digital tools to streamline collections of robust data during normal patient visits while incorporating randomization to answer critical research questions and inform decision‐making by regulators, payers, and other stakeholders.

For patients, trial participation and routine care are ideally indistinguishable. These approaches are therefore most appropriate for chronic conditions with United States Food and Drug Administration (FDA)‐approved treatments available where further evidence is needed to expand drug labels and improve care delivery or in public health emergencies where repurposed drugs can provide a first‐line response. For example, in the RECOVERY trial in the United Kingdom, patients hospitalized with COVID‐19 were automatically enrolled and randomized to receive drugs such as dexamethasone that were already widely used for other conditions. Point‐of‐care trials may have the added benefit of engaging more people in clinical research by making trial participation accessible for a broader range of clinical sites, providers, and patients that have historically been excluded from the research enterprise.

However, despite the potential of point‐of‐care trials, clinical care and research have traditionally been viewed as two distinct activities with separate systems of oversight. The line between research and care can become blurred in point‐of‐care research, creating confusion for researchers and patients in the absence of appropriate informed consent models and guidance. It is therefore critical to discuss and anticipate ethical considerations for obtaining patient informed consent within point‐of‐care trials, especially as these trials may serve more diverse populations than traditional explanatory trials. In this perspective, we present technical and practical considerations for obtaining informed consent in point‐of‐care research intended to address important pharmacoepidemiologic questions regarding treatment effectiveness.

2. CONSENT AT THE TECHNOLOGY AND INFRASTRUCTURE LEVEL

Point‐of‐care trials ideally leverage the EHR for consenting patients, consistent with a larger movement toward establishing learning health systems in academic medical centers. Some health systems, like the U.S. Department of Veteran's Affairs (VA), have modified their EHR systems to allow for informed consent on the physician's menu and can consent patients in clinician office settings. Consenting patients in‐office requires a retooling of EHR systems to make them more efficient for frontline clinicians. Point‐of‐care trials conducted across multiple sites and inclusive of multiple health systems must account for the significant variance in EHRs across sites and systems, and standardizing EHR systems across sites requires significant time and resources. Physicians and trial staff at the VA have stressed the importance of driving down clicks to reduce clinician burden and burnout. ⁶ , ⁷

Other sites not equipped with modified EHRs may obtain virtual consent via web portals or by phone when not physically in the clinic. While integration of the consent process into EHR can be tricky and cost‐prohibitive for community sites, other forms of consent pose additional problems such as decreased patient accessibility and increased clinician workload. Consenting via web portals or by phone may be difficult for patients without access to reliable internet or cell phone service, and these methods also add another layer of administrative complexity as they are not integrated into existing clinical workflows.

3. INFORMED CONSENT IN CLINICAL PRACTICE

One major outstanding question in point‐of‐care research has centered around who administers consent to patients. For some studies, consent is obtained by trained research personnel, not the treating clinician. ⁸ Some research suggests that nurses have been more comfortable consenting patients than physicians and that the doctor‐patient relationship may be better preserved when treating physicians are not engaged in the task of consenting patients. ⁹ However, consent approaches that embody the notion, spirit, and guided practice of patient partnership in point‐of‐care research, where clinical equipoise is front and center and time is given to balance power dynamics and differentials, may help all qualified research personnel (e.g., physician researchers, nursing professionals, clinical research associates, certified health educators, etc.) effectively and comfortably deliver informed consent. ¹⁰ , ¹¹ Research teams using a patient partnership model may involve patients or patient representatives in the development of study protocols or recruitment strategies and may provide context‐specific guidance about the appropriateness of informed consent delivery which varies by trial. ¹² Patient partnership approaches in point‐of‐care research can not only preserve the patient‐doctor relationship but could importantly ease operational and regulatory burdens and/or workloads for busy providers through stable patient follow‐up, engagement, and retention needed to generate relevant and reliable patient outcomes data. One study surveying pragmatic clinical trial researchers showed that fewer than half used patient partnership approaches, ¹² demonstrating considerable room for improved uptake of these strategies.

Some health systems implementing point‐of‐care research have used novel consent processes that are worth noting. Two‐step or “just‐in‐time” consent is one example of a consent model being used for research occurring in clinical practice. Conducting consent in two stages—the first stage which provides information about general research procedures and the second which provides information about the specific experimental intervention—may reduce anxiety, confusion, and information overload for patients that is typically associated with informed consent. In this model, only patients randomized to the experimental treatment are subject to both stages of consent, whereas patients randomized to the control treatment only complete the first stage. ¹³ This model may only be appropriate for trials that use a standard‐of‐care comparator arm and in which blinding is impractical or impermissible, which are common features of point‐of‐care trials.

This approach may benefit care providers with existing treatment relationships who feel uncomfortable approaching patients for difficult consent conversations. ¹³ In addition, discussing randomization during the consent process may be perceived as less deceptive and more straightforward and respectful to patients, and may improve patient comprehension of research procedures, which would be an improvement over current informed consent protocols that prioritize legal compliance over patient understanding. ¹⁴ , ¹⁵

4. CONSENT AND THE LARGER REGULATORY, POLICY, AND ETHICS LANDSCAPE

The regulatory burden associated with point‐of‐care trials is currently high, partially due to the nascent nature of this approach to clinical research. There is a need for federal guidance from regulators about point‐of‐care trial acceptability in general, including informed consent practices.

Respect for persons and risk are two important concepts relevant to decision‐making about informed consent delivery. The concept of respect for persons or treating research participants as ends in and of themselves rather than just means to produce study results is a core ethical obligation that is typically satisfied through traditional informed consent processes. ¹⁶ Risk is also an important factor in informed consent delivery decisions. Notably, the 21st Century Cures Act allows for consent requirements to be waived in minimal‐risk scenarios with appropriate safeguards. ¹⁷ Point‐of‐care trial approaches applied to repurposed or already‐approved therapies, with their focus on leveraging data from EHRs collected during routine visits, could potentially meet criteria of minimal‐risk consideration for waivers or alterations of informed consent. However, an ethically sound approach to determining the appropriateness of consent waivers in point‐of‐care research requires thoughtful discussions around the concept of risk relative to the study question(s) and design (i.e., comparative effectiveness of one or more treatments, standard of care, etc.). ¹⁸ Endpoints selection (i.e., mortality, disability, safety measures, side effects, etc.) is also relevant, as endpoints such as mortality or side effects are serious and may signify higher risk. Waivers or modifications of informed consent may be less appropriate for trials in which the intervention is novel, under investigation for regulatory submission, or has unclear safety data.

Two previously conducted point‐of‐care trials can help exemplify these considerations. First is the MOMs trial, which compared the initiation of methadone vs. buprenorphine in patients experiencing opioid dependency during pregnancy. The primary endpoint in the trial was 'length of stay' and the secondary endpoint was 'retention in medication treatment' for opioid use disorder through delivery, and patients were recruited through the health system EHR. Clinicians obtained informed consent for the trial during the patients' health care encounters. ⁹ Contrast this study with the ABATE trial, which compared antiseptic bathing for all patients and nasal ointments for patients with carriers of methicillin‐resistant Staphylococcus aureus (MRSA) vs. routine bathing in reducing multidrug‐resistant infections. ¹⁹ The ABATE trial's primary outcome was the presence of MRSA or vancomycin‐resistant Enterococcus clinical cultures derived from the participating sites, and study staff also used the EHR to identify patients and record outcomes. The trial was completed under a waiver of informed consent. These two trials demonstrate the heterogeneity of research questions that point‐of‐care trials may be deployed to answer, and the need for trial‐specific evaluation of respect for persons and risk relevant to decisions about informed consent delivery (or lack thereof). The MOMs trial, involving initiation of medication to treat opioid use disorder, necessitates informed consent conversations with patients due to potential differences in patient preferences, the possibility of side effects, and the need for open communication between patient and clinician for optimal outcomes and patient safety. The ABATE study, by comparison, is acceptable for a waiver of consent because it studied two products with a low probability of harm and no known risks of use, consistent with quality improvement studies in which patients are less likely to have meaningful preferences or adverse experiences.

In keeping with bioethical principles of respect for persons, trialists should consider obtaining informed consent even if trials meet the regulatory criteria for waivers or alterations. For one, the informed consent process allows trial staff to discuss with patients how their data will be used and to educate them about trial conduct. Some research suggests that waivers or modifications of informed consent may impact public support for participation in research due to a perceived rollback of patients' rights, which could affect representative enrollment in point‐of‐care trials. ²⁰

Despite there being good ethical reasons for obtaining consent from patients, this notification may impact the “real‐world” nature of the study if participants' behavior changes as a result of notification. In addition, notification can create a resource issue, as both individual‐ and group‐level notification strategies require prior planning and may necessitate dedicated funding for the development of materials, such as emails, posters, or flyers for dissemination. ²¹ It is possible that obtaining full informed consent from patients in point‐of‐care trials could lead to an unwanted information overload. More empirical study is needed to determine in which contexts patients would prefer to be notified about their inclusion in a study, rather than their notification becoming another stressor in addition to managing their presenting health problem. This research could help inform guidance documents as to when waivers and modifications of consent are ethically appropriate.

Institutional review board (IRB) personnel and point‐of‐care research teams are, therefore, highly encouraged to disseminate their current practices and thought processes around concepts of risk and the appropriateness of consent waivers in point‐of‐care research. Research initiatives, like the NIH Pragmatic Trials Collaboratory, are also encouraged to disseminate their informed consent practices for pragmatic trials that utilize a point‐of‐care trial approach. These bodies, as well as other research groups that produce scholarship on ethical dimensions of point‐of‐care trials, can help contribute to an evidence base from which federal regulators such as the FDA can draw for creating robust guidance documents.

5. FUTURE DIRECTIONS AND AREAS FOR FURTHER RESEARCH

Researchers engaged in point‐of‐care trials stand to benefit from increased consensus around preferred models of consent and determining who is responsible for consenting patients. There is an additional need for further empirical scholarship on patient preferences in the informed consent process to improve the patient experience and to ensure that the point‐of‐care approach can be further deployed without damaging patients' perceptions of clinical research participation.

Reducing administrative burdens on frontline clinicians and in trial initiation is a major goal in achieving sustainable point‐of‐care research infrastructure. The high level of burden places additional constraints on sites and providers raises concerns about clinician burnout and makes it such that only highly‐resourced sites can participate in point‐of‐care research. Making the consent process less onerous may improve clinician attitudes about participating in point‐of‐care clinical trials, thus increasing uptake of the approach. Additional guidance from regulators could help the research enterprise be more informed and aligned on best practices, reduce complexity, and remove uncertainty for trial sponsors looking to fund point‐of‐care research.

6. CONCLUSIONS

Point‐of‐care trials have the potential to efficiently generate practically relevant evidence in routine care settings. Yet, like all nascent trial designs, point‐of‐care trials hold novel and unique ethical considerations that must be explored, such as informed consent, along with a need for dissemination of best practices and lessons learned when an ethical oversight path has been selected or taken. It is therefore vital for health system stakeholders to collaborate around the development, implementation, and testing of innovative approaches that center patients as partners in point‐of‐care research that can address important pharmacoepidemiologic questions around treatment effectiveness in the real world.

CONFLICT OF INTEREST STATEMENT

Dr. Rachele Hendricks‐Sturrup is a Director of the Board for Public Responsibility in Medicine and Research (PRIM&R).

Propes C, Locke T, Hendricks‐Sturrup R. Landscape of informed consent practices and challenges in point‐of‐care clinical trials. Learn Health Sys. 2025;9(3):e10467. doi: 10.1002/lrh2.10467