Yonsei Med J.  2011 Sep;52(5):701-716. 10.3349/ymj.2011.52.5.701.

Are You "Tilting at Windmills" or Undertaking a Valid Clinical Trial?

• Steeves JD
• Zariffa J
• Kramer JL

• KMID: 1108061
• DOI: http://doi.org/10.3349/ymj.2011.52.5.701

Abstract

In this review, several aspects surrounding the choice of a therapeutic intervention and the conduct of clinical trials are discussed. Some of the background for why human studies have evolved to their current state is also included. Specifically, the following questions have been addressed: 1) What criteria should be used to determine whether a scientific discovery or invention is worthy of translation to human application? 2) What recent scientific advance warrants a deeper understanding of clinical trials by everyone? 3) What are the different types and phases of a clinical trial? 4) What characteristics of a human disorder should be noted, tracked, or stratified for a clinical trial and what inclusion /exclusion criteria are important to enrolling appropriate trial subjects? 5) What are the different study designs that can be used in a clinical trial program? 6) What confounding factors can alter the accurate interpretation of clinical trial outcomes? 7) What are the success rates of clinical trials and what can we learn from previous clinical trials? 8) What are the essential principles for the conduct of valid clinical trials?

Keyword

Human; research; protocol; guidelines; translation; neurology

MeSH Terms

Animals
Clinical Protocols
Clinical Trials as Topic/ethics/*methods
Disease Models, Animal
Female
Humans
Male
Outcome Assessment (Health Care)
Pregnancy
Translational Medical Research

Figure

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  Fig. 1 Copy of the Pablo Picasso sketch of Don Quixote (1955), copyright holder unknown, but presumed to be copyrighted. First appeared in August 18-24 issue of the French weekly journal Les Lettres Françaises in celebration of 350th anniversary of the first part of Cervantes' novel Don Quixote. Used here in a completely non-profit and non-commercial manner for scholarly research and teaching purposes, under "fair use or fair dealing" exemptions.

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  Fig. 2 Summary chart of a translational path for a therapeutic intervention from scientific discovery to approval for clinical use.

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  Fig. 3 The necessary inclusion and exclusion criteria to qualify as a trial subject can create a funnel effect that substantially reduces the number of trial participants that can enroll in a human study. This can be a very difficult challenge for rare (small incidence) disorders and to generate sufficient participants may require recruitment from multiple center trials at even the earliest phases of a study.

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  Fig. 4 International Classification of Functioning, Disability and Health (abbreviation ICF) is a taxonomic structure or bio-psycho-social model (from WHO) integrating medical and social influences on disability. Therefore, meaningful recovery is a continuum across the ICF Domains where we measure: improvements (or impairments) in the function of body tissues, capacities (or limitations) in the daily activities of the individual, and ultimately, at the highest and most complex level, the person judges their performance (or restrictions) to participate within their community. To date, participation outcomes have not been routinely used as a primary outcome in a clinical trial.

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