Pharm-Olam is experienced in dealing with ventilator-associated studies and consenting patients in an Intensive Care Unit (ICU) setting due to our experience in running numerous global Pneumonia studies from Phase II to Phase IIIs. You can learn more about our experience and CRO services in infectious disease and vaccines here.
In this article, we will look at challenges surrounding the issue of securing patient consent in ventilator-associated studies.
Consideration of Ventilator-Associated Consent & COVID-19 Application
With the COVID-19 pandemic, we understand the importance and reliance on ventilators to support afflicted patients with the disease when fighting severe symptoms. As we are ramping up clinical trials to combat COVID-19, the application of best practice for consenting patients who are on a ventilator is absolutely applicable. This article and the helpful resources included at the bottom, may prove helpful to you in planning your COVID-19 clinical trials.
Additionally, and of note, when a person is on a ventilator, his or her risk for developing ventilator-associated pneumonia (VAP) is significant. Dartmouth-Hitchcock says that roughly 15% of people on ventilators will develop VAP and of those, 50% will likely die from the condition. Now, let's discuss the challenges.
Understanding the Challenge of Consent
At Pharm-Olam, we want to do our part to help explain VAP and the issues surrounding clinical studies that center on the condition. We have completed numerous studies that involved the issue of consenting ventilator-assisted patients. Together, we can leverage best practices to test drug therapies for ventilator-associated pneumonia more effectively, and these practices will be certainly beneficial to COVID-19 trials.
Conducting clinical research studies often means juggling several different sites and the varying regulations that exist in each location [site] and within each participating country. Understanding and mapping the regulatory environment of your sites and countries as it relates to patient consent is critical to study success and efficient patient enrollment. When studying patients on ventilators, especially those that are confined to Intensive Care Units (ICUs), the issue of consent becomes even more complex and paramount to study enrollment success.
Understanding the Patient Consent Process
Different countries have different regulations concerning the consent of unconscious or sedated patients. In some cases, a doctor can give consent, but it is only temporary. Doctor-provided consent lasts until the study researchers reach the family or the patient regains consciousness. If the patient is in a country that allows the family to consent on behalf of the sedated or unconscious person, that consent only holds until the individual regains consciousness. Once the patient is awake and lucid, he or she must renew their consent.
Not only does consent need to follow through at each step for it to be valid, but researchers are tasked with tracking that information.
Managing Consent Data Across Sites and Countries
If all countries had the same requirements and consent only needed to be given once, it would only be a matter of checking a box. However, multi-site studies do not always have this advantage. In our recent work on the Phase 3 study that employed a mAb drug as a complementary treatment to the SOC treatment of VAP, this was a critical concern because many of the patients were unconscious or sedated when their participation in the study began. We had to abide by each country's definition of consent and, once we worked to obtain valid consent, we had to track all that information. Further, the state of each patient’s consent could change based on their progression. These changes also needed to be monitored and recorded.
In normal circumstances, a site-level consent tracker is enough, but you should also account for this and the need to update consent status within your electronic Case Report Forms (eCRF). If you cannot achieve this within your electronic data collection (EDC) system, you will likely need to develop an internal log and a paper trail so that every consent can be collected and documented as needed.
Understanding Consent During the COVID-19 Pandemic
Consenting patients during the COVID-19 pandemic presents its own challenges. Many clinical trials concerning the coronavirus will involve mechanically ventilated patients. However, researchers will not be able to obtain consent in the traditional way. Relatives and other legally acceptable representatives will likely not be permitted into the same space as COVID-19 patients. They likely cannot come to the site in person to give consent due to prohibited visits to infected area. You will need to think about this aspect and how to achieve a relative’s consent. The only alternative is to require either independent physician consent in countries where that is allowed (which could be a limiting factor) or verbal consent by relatives where it is approved. That may change. As COVID-19 trials are starting up, new guidance to speed up are being issued daily. Suggestions as to how to get consent from unconscious patients with coronavirus will fall to the FDA, EMA and other regulatory agencies, and that guidance could change. Sponsor companies looking to test a drug or treatment that concerns COVID-19 should make sure that they choose a CRO that is experienced in managing consent so that the study can be on the fastest track possible. Having a thoughtful and pre-planned approach to the complexities of securing patient consent from ventilator-assisted patients will be critical to timely enrollment in your study.
Best Practices in Consenting Ventilator-Assisted Patients
Consenting patients in ventilator-associated studies may mean that researchers need to take a different approach. This may involve selecting sites in countries that allow informed consent to be provided by families or doctors for the utmost flexibility and responsiveness to patient enrollment. In addition, consent trackers and EDC systems need to be robust enough to accept multiple inputs and record patient consent statuses as they change based on the consciousness and coherency of the study participants.
As far as COVID-19, research in that space is going to take the existing issues with VAP consent and add the additional complication of securing consent during quarantine. We are prepared to meet that challenge because we have extensive experience with this type of study challenge.
Helpful Resources Regarding Patient Consent in ICU Settings:
- Ecarnot, F., Quenot, J. P., Besch, G., & Piton, G. (2017). Ethical challenges involved in obtaining consent for research from patients hospitalized in the intensive care unit. Annals of translational medicine, 5(Suppl 4), S41. https://doi.org/10.21037/atm.2017.04.42
- Matei, M. 2013). Intensive Care Unit Research and Informed Consent: Still a Conundrum. American Journal of Respiratory and Critical Care Medicine, 187(11), 1164-1166. https://www.atsjournals.org/doi/full/10.1164/rccm.201303-0590ED
- Verceles, A. C., & Bhatti, W. (2018). The Ethical Concerns of Seeking Consent from Critically Ill, Mechanically Ventilated Patients for Research - A Matter of Possessing Capacity or Surrogate Insight. Clinical Ethics, 13(3), 107–111. https://doi.org/10.1177/1477750918762350