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Little Clinical Research Conducted
During the 2009 Pandemic

By Amesh A. Adalja, MD, FACP, May 17, 2013

During the 2009 H1N1 influenza pandemic, clinicians continually needed to devise strategies to treat severely ill patients. Because 2009 H1N1 was the first influenza pandemic to occur in the era of modern critical care, it was not definitively known whether certain interventions were applicable. This gap in knowledge could be answered only by real-time research aimed at providing guidance to be used during the pandemic (and as preparation for the next). The National Biodefense Science Board has labeled scientific investigations “an integral component of disaster planning and response,”1 and Lurie et al write that scientific research “is essential to address the most pressing knowledge gaps presented by public health emergencies.”2 While many case and anecdotal reports were published during the pandemic, rigorous research is needed to answer crucial clinical questions during public health emergencies. Researchers from the International Respiratory and Severe Illness Center (INTERSECT) recently published the results of a systematic review cataloging nonantiviral studies conducted during the pandemic to gauge the quality, topics, and methodology of intrapandemic research.3

Only 7 Studies Identified

Using extensive searching based on relevant keywords in several databases, the INTERSECT researchers identified 7 articles (from an initial list of 2,452) that met the criteria of being a randomized controlled trial (RCT), a prospective cohort study, or a systematic review/meta-analysis published in English between March 2009 and January 2012.3

Some important features of the included studies were:

  • None was conducted in the United States;
  • Corticosteroids were studied in 3 publications;
  • Convalescent plasma was studied in 1 publication;
  • Extracorporeal lung support was studied in 3 publications; and
  • All were observational prospective cohort studies; none were RCTs.

The 3 corticosteroid studies did not identify a benefit to administering corticosteroids, while the convalescent plasma trial identified a mortality benefit in the treatment group. The 3 extracorporeal support trials revealed mixed results, with 1 study showing higher mortality, 1 lower, and another no difference.3

Quality of Studies High

An instrument was used to evaluate the quality of studies for selection, comparability, and outcome; 4 of the 7 studies received the highest possible score of 9. The remaining 3 studies (convalescent plasma and 2 extracorporeal) scored 6 or 7, reflecting the generally high quality of the included studies.

Many Barriers to Research During Emergencies

Conducting high-quality research during a public health emergency is a daunting task, as evidenced by the dearth of studies during the 2009 influenza pandemic. However, such research is essential to inform the response and mitigate the potential consequences of the event, whether it is an influenza pandemic or an earthquake. For example, during the H1N1 pandemic, it was important for clinicians to know that corticosteroids would not benefit—and could potentially harm—their patients, a fact established by high-quality research conducted in the midst of the pandemic.

In an editorial accompanying the INTERSECT study, Kissoon and Marshall list some of the myriad obstacles facing researchers in these situations, including funding sources, protocol development, institutional review board approval, and multi-institutional collaboration. However, as they note, not conducting research creates “lost opportunities to understand and evaluate resource needs and therapies.”4

The elements that Lurie et al identify as key components of a research response during a public health emergency include many endeavors that would ameliorate the barriers identified and merit implementation, chief among which are a national public health emergency research review board and an incident commander for research.2

References

  1. Call to action: include scientific investigations as an integral component of disaster planning and response. Washington, DC: National Biodefense Science Board; 2011. www.phe.gov/Preparedness/legal/boards/nbsb/Documents/nbsbrec14.pdf. Accessed May 14, 2013.
  2. Lurie N, Manolio T, Patterson AP, et al. Research as a part of a public health emergency response. N Engl J Med 2013;368:1251-1255.
  3. Ortiz JR, Rudd KE, Clark DV, et al. Clinical research during a public health emergency: a systematic review of severe pandemic influenza management. Crit Care Med 2013;41:1345-1352.
  4. Kissoon N, Marshall J. Research during pandemics: has the horse left the barn? Crit Care Med 2013;41:1381-1383.