Index
Module 2 • Research Methods
Research Design, Biostatistics & Literature Evaluation
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Data Tables
Research Design, Biostatistics & Literature Evaluation
Julie E. Farrar ~3 min read Module 2 of 20
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Research Design, Biostatistics, and Literature Evaluation

D.The Common Rule – Created in 1991 as uniform ethical standards for research after a series of exposures

of unethical research misconduct, such as the Tuskegee syphilis study. This rule defined human participant

research, developed the process of informed consent, and established the requirement of institutional review

boards (IRBs) (JAMA 2017;317:1521-2).
1

The Common Rule has undergone major changes, with most implementation occurring in 2019 (Chest

2019;155:272-8). These included the following:

New categories and definitions of exempt or excluded research studies

Allowance of a single IRB for multi-institutional studies

Exclusion of public health surveillance as research

d.Requirement of concise, focused consent forms and online posting of consent as applicable

Allowance of broad consent for identifiable biospecimens in future unspecified research studies

III.PRACTICAL CHALLENGES TO CRITICAL CARE RESEARCH
A.Institutional Review Board (IRB)
1

IRB of record versus institutional versus independent versus relying IRB

2Important considerations for a priori planning

Differences: Processes, time, cost, forms, etc.

Central IRB

B.Research Subject Recruitment – To maximize external validity, research subjects recruited for participation

in a clinical trial should be representative of the general population of patients with the disease or syndrome.

1

Critical care is exemplified by the provision of supportive care for the treatment of diseases and

syndromes.

Diseases are characterized by the specific test used to identify the pathophysiologic process.

Syndromes are often identified by the presence of a constellation of signs and symptoms that suggest

the presence of a disease that exists across a spectrum of severity.

2Recognizing the attendant syndrome is critical for the timely provision of therapy and, in research,

subject recruitment.

Heterogeneity in syndromes challenges the ability to identify subjects with similar severity or

probability for similar clinical outcomes for participation in clinical research.

In addition, heterogeneity challenges the ability to interpret the results from dissimilar populations,

even though they may have a single syndrome in common.

Discrepancies between results from basic and early clinical studies versus adequately powered

controlled trials show that surrogate outcome measures (e.g., organ function) or biomarkers may not

reliably predict clinical benefit (Am J Respir Crit Care Med 2015;191:1367-73).
3

Unique to critical care clinical research is the need to enroll subjects similar in acuity or at a similar

stage in the process of their syndrome to allow meaningful comparisons.

4

Use of non-standardized definitions and lack of power complicate data synthesis and meta-analysis (Am

J Respir Crit Care Med 2014;189:1469-78).
5

Selection of end points should be based, in part, on the ethical values outlined previously. End points

should provide social value and have scientific validity. A growing area of emphasis in research is on

the need to design patient-centered studies (JAMA 2012;307:1583-4). (Example: Positive vs. negative

neurological outcome, rather than mean change in modified Rankin Score.)

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