Medical Grand Rounds – Dr. David Maslove: Pandemic Science: the good, the not-so-good, and the ugly

Dilakshan Srikanthan, MD/PhD Candidate (Translational Medicine)

For the last Medical Grand Rounds (MGR) for the month of February, we had the pleasure of hearing from Dr. David Maslove about the effects of the COVID-19 pandemic on current affairs in academic medicine. Dr. Maslove is an internist and intensivist at Kingston Health Sciences Center and an Associate Professor cross-appointed in the Departments of Medicine and Critical Care. Dr. Maslove’s presentation summarized the positive and negative impacts of the pandemic on academic medicine, and what we can learn from them.

Dr. Maslove opened on a positive note, discussing how the pandemic has improved academic medicine by 1) identifying new models of clinical trial design, 2) implementing new models of collaboration, and 3) employing new models of publishing. Notably, the significance of platform trials was thoroughly assessed throughout the pandemic. Platform trials focus on the disease rather than a treatment, in essence, allowing a single trial to assess various treatments (1). Not only is this a time-efficient way of conducting clinical trials, but it is also resource-efficient, as all participants can be recruited to one trial and assigned to different arms. The RECOVERY trial was a trial that unearthed the potential of platform trials during the pandemic. Within 1 year of declaring a worldwide pandemic, this trial had enrolled approximately 47 thousand patients and had produced conclusive results on the efficacy of 7 possible treatment types (2,3). Another noteworthy platform trial is the REMAP CAP trial which predates the pandemic, however, also enrolled COVID-19 patients (4). This trial made tremendous contributions to the standard of care for COVID-19, based on disease severity. Benefits of platform trials include the usage of multiple treatment arms and continuous testing; however, platform trials require the use of Bayesian statistics rather than the traditional frequentist approach, which is often more complex and difficult to grasp. Furthermore, platform trials are relatively new, and their true potential remains to be seen.

While the concept of international collaboration is not new, it was paramount in the response to the COVID-19 pandemic. International collaborations have always existed in critical care, for example, in developing the guidelines for septic shock care (5). As previously mentioned, the REMAP CAP trial contributed tremendously to the COVID-19 standard of care, however, it would not have been possible without international collaborators (4). Dr. Maslove highlighted other successful trials that have emerged in the pandemic that owe their success to international collaboration, including the SPRINT- SARI trial and the GenOMICC trial (6,7). Notably, the genetic mechanisms of critical illness in COVID-19 were published within 1 year of the start of the pandemic, attesting to the impact of global collaborations in genetics research. While international collaborations allow improvements in sample size, representation, and inclusivity, they are also difficult to coordinate and maintain.

Dr. Maslove emphasized that the pandemic has resulted in the biological homogeneity of certain diseases. Traditionally, identifying biologically homogeneous populations is very difficult, and recruiting a sufficient sample size when you do identify homogeneous populations presents challenges. While conditions like sepsis tend to be heterogeneous, COVID-19-induced sepsis allowed patients to be viewed as homogeneous due to the shared underlying etiology. As such, scientists reaped the benefits of studying biologically homogeneous states, whereby patients are more likely to respond in the same way.  

One of the most prominent platforms that came to light in academic medicine during the pandemic is the use of preprint servers, permitting the distribution of manuscripts that are not yet peer reviewed. While preprint servers enable the rapid dissemination of research findings, they also present challenges in publication ethics and integrity. Dr. Maslove highlighted how preprint findings often make their way into the media and thus are prone to the rapid spread of disinformation in the public. While there are benefits associated with preprint servers such as accelerated discovery and knowledge translation, they should be approached with caution as they can lead to false starts and unsupported claims.

Following Dr. Maslove’s presentation, the graduate students of the Translational Medicine (TMED) program had the privilege of continuing the discussion with him. The discussion delved into the implications of the pandemic on patients, as well as relevant equity, diversity and inclusivity (EDI) initiatives, and representation in the lay press. The COVID-19 pandemic has revealed urgent needs, truths, and challenges in academic medicine, requiring deep reflection for moving forwards in the post-pandemic era (8). On behalf of the TMED class, I would like to thank Dr. Maslove for sharing his time and valuable insights.

References

1) Berry, Scott M., et al. “The Platform Trial.” JAMA, vol. 313, no. 16, 2015, p. 1619., https://doi.org/10.1001/jama.2015.2316

2) “Dexamethasone in Hospitalized Patients with Covid-19.” New England Journal of Medicine, vol. 384, no. 8, 2021, pp. 693–704., https://doi.org/10.1056/nejmoa2021436.

3) “Colchicine in Patients Admitted to Hospital with Covid-19 (Recovery): A Randomised, Controlled, Open-Label, Platform Trial.” The Lancet Respiratory Medicine, vol. 9, no. 12, 2021, pp. 1419–1426., https://doi.org/10.1016/s2213-2600(21)00435-5.

4) “Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.” New England Journal of Medicine, vol. 385, no. 12, 2021, pp. 1147–1149., https://doi.org/10.1056/nejmc2108482.

5) “A Randomized Trial of Protocol-Based Care for Early Septic Shock.” New England Journal of Medicine, vol. 370, no. 18, 2014, pp. 1683–1693., https://doi.org/10.1056/nejmoa1401602.

6) Murthy, Srinivas, et al. “Characteristics and Outcomes of Patients with Covid-19 Admitted to Hospital and Intensive Care in the First Phase of the Pandemic in Canada: A National Cohort Study.” CMAJ Open, vol. 9, no. 1, 2021, https://doi.org/10.9778/cmajo.20200250.

7) Pairo-Castineira, Erola, et al. “Genetic Mechanisms of Critical Illness in Covid-19.” Nature, vol. 591, no. 7848, 2020, pp. 92–98., https://doi.org/10.1038/s41586-020-03065-y.

8) Maslove, David M., and J. Kenneth Baillie. “Two Key Takeaways from a Year of Pandemic Research.” Critical Care Medicine, Publish Ahead of Print, 2021, https://doi.org/10.1097/ccm.0000000000005078.