Ethical Considerations during the Informed Consent Process for Acute Ischemic Stroke in International Clinical Trials

Abstract

Introduction: Obtaining informed consent from acute ischemic stroke patients poses many challenges, especially in the context of a research setting. Specifically, consenting for alternative acute ischemic stroke treatments to the standard of care, Tissue Plasminogen Activator (tPA), can cause delays leading to increased time to reperfusion and worse outcomes. Objectives: We sought to investigate the experiences of researchers in existing active-control trials in acute ischemic stroke comparing investigational therapy to tPA in order to identify the approaches and challenges in obtaining informed consent in this unique patient population. Methods: Out of 401 articles evaluated, 14 trials met inclusion criteria of patients receiving IV tPA vs alternative treatment within 4.5 hours of onset of symptoms for acute ischemic stroke. Trial representatives were emailed by the study team with a request for a copy of their patient consent form, other documents related to informed consent, and to complete a survey concerning aspects of the consent process. Results: Of the 6 trials conducted across 6 continents that completed the survey in its entirety, 2 were ongoing, 4 were published between 2009 and 2016, and the median NIHSS for each published trial was at least an 8. All published trials in the sample stated that informed consent was obtained, but only half reported involvement of a research ethics committee. Although 3 trials performed in Europe or Asia reported directly consenting 75-100% of enrolled patients, the median NIHSS for these trials represented a moderate stroke. Trials with 75-100% of patients directly consented had shorter door to treatment (DTT) times than trials that directly consented less than 50% of enrolled patients. 5 trials allowed consent by proxy, but only 2 of those trials also required patient assent. 4 trials had translators available and translated consent documents, and these trials had longer DTT times. All trials relied on experienced providers or dedicated research coordinators to obtain informed consent; however, only 2 of 6 trials mentioned specific training with regards to informed consent skills. Conclusions: The current informed consent process is not transparent and poses challenges to investigators in the USA directly comparing tPA to an alternative treatment. International differences in the standards of informed consent, such as deferred consent, may have allowed more patients with moderate strokes to provide direct consent after treatment administration without delaying DTT time. While targeted and innovative approaches for informed consent are needed to improve patient outcomes, we must balance protecting the autonomy of individuals whose willing involvement enables such pivotal discoveries. The stroke community must aim for efficiency, transparency, and inclusion of patients of diverse backgrounds in the informed consent process so that therapeutic advances are possible.

Do National and International Ethics Documents Accord With the Consent Substitute Model for Emergency Research?

“…We chose this model because previous research has demonstrated the difficulties involved in seeking informed consent in emergency medical research. [17][18][19][20][21][22][23][24][25][26] Largent et al provide an alternative to unsatisfactory consent processes used in this context. Furthermore, their model continues to be cited regularly in the emergency research literature.…”

“…We compared the five conditions of the consent substitute model with the emergency research provisions within international and national ethical frameworks, to determine whether it could be employed by researchers adhering to these frameworks. We chose this model because previous research has demonstrated the difficulties involved in seeking informed consent in emergency medical research 17–26 . Largent et al provide an alternative to unsatisfactory consent processes used in this context.…”