Published ahead of print on August 9, 2006
Clin J Am Soc Nephrol 1: 1115-1116, 2006
© 2006 American Society of Nephrology
doi: 10.2215/CJN.02020606
Clinical Research Methods in CJASN
Chi-yuan Hsu*, and
Harold I. Feldman
* Department of Medicine, University of California, San Francisco, San Francisco, California; and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Address correspondence to: Dr. Chi-yuan Hsu, University of California, San Francisco, 513 Parnassus Avenue, 672 HSE, San Francisco, CA 94143-0532. Phone: 415-353-2379; Fax: 415-476-3381; E-mail: hsuchi{at}medicine.ucsf.edu
Epidemiology and biostatistics have played an increasingly important role in the study of renal disease and, therefore, the nephrology literature. As a result, many nephrologists seek opportunities to improve their ability to read this literature critically. Responding to this need, we begin a series of articles in this issue of the Clinical Journal of the American Society of Nephrology (CJASN) that will highlight major clinical research methods that many of CJASN’s contributors use in their studies of renal diseases. Although this series will cover only a portion of the large set of methods and issues that are relevant to the conduct of clinical research in nephrology, it will be extended periodically to expand opportunities for CJASN readers to be exposed to the full array of clinical research tools.
The number of published clinical research studies has increased greatly in the past decade. Since 2000 alone, Medline contains nearly 24,000 citations that both address kidney disease and are identified as using epidemiologic study methods. Clinical epidemiologic studies can be categorized according to broad areas of inquiry listed in Figure 1. Although questions in these areas can be informed by a variety of study methods, each is addressed most commonly by specific study designs. For example, studies of cause and prognosis often utilize cohort designs, whereas studies of therapy frequently utilize the clinical trial designs. Study designs also can be classified according to whether their focus is to describe patterns of disease (descriptive studies) or examine hypotheses about exposure–disease relationships (analytical studies). The latter can be divided further into those in which the investigator examines exposure–disease relationships as they naturally occur (observational studies) and those in which there is modification or creation of the study conditions (experimental studies). Figure 2 lists some of the most common clinical research study designs.
The initial four papers of this series derive from the ASN's Post-Graduate Education course delivered at the 2005 Annual Meeting in Philadelphia: "Critically Approaching the Literature: Applying the Principles of Epidemiology and Biostatistics." Thadhani and Tonelli’s article in this issue on cohort research will be followed by contributions that address case-control methods, clinical trials, and meta-analysis, also provided by speakers from the ASN course. In addition to covering fundamental epidemiologic study designs, this series will review related concepts such as bias, confounding, and biostatistical tools such as confidence intervals and multivariate regression. All of our contributors will exemplify these topics through discussion of published studies in renal medicine.
Thadhani and Tonelli’s article in this issue discusses cohort studies, a powerful method of observational research that tracks people forward in time from exposure to outcome. Cohort studies can be exceedingly potent designs, especially when using large data sets that record clinical attributes and outcomes over time, such as the US Renal Data System data set, and data sets from large health maintenance organizations and dialysis chains. Increasingly, prospective research that explores multiple scientific questions that are not addressed feasibly through randomized, clinical trials use the cohort method, such as the National Institute of Diabetes and Digestive and Kidney Diseases’ Chronic Renal Insufficiency Cohort Study (1), CKiD: A Prospective Cohort Study of Kidney Disease in Children (http://www.statepi.jhsph.edu/ckid/), and the African American Study of Kidney Disease and Hypertension (AASK) cohort study (2).
The second contribution will cover case-control studies, another observational study design that efficiently works in reverse by tracing back from outcome to exposure. Case-control research increasingly has played a role in the nephrology literature, providing efficiencies over cohort study designs when the outcomes of interest are rare. Case-control studies also often provide opportunity to supplement exposure data beyond those that are available in preexisting clinical or administrative data sets by virtue of the relatively small number of patients who are required compared with cohort research.
The third contribution will provide an overview of randomized, controlled trials, which are the gold standard method for providing the most unbiased estimate regarding the effect of a treatment. Clinical trials have provided unique opportunities to address questions of dialysis dose (3), progression of chronic kidney disease (4), and anemia management (5), among many others. Despite their clear advantage with respect to the control of confounding, clinical trialists must overcome substantial logistical challenges, including their high cost. As well, the generalizability of findings from clinical trials often is limited by the selected nature of both recruitment and clinical care that is provided during the study.
The fourth contribution will cover systematic reviews and meta-analyses, which traditionally have been used to synthesize the findings of a series of clinical trials, each without a definitive conclusion. More recently, meta-analyses of observational research (e.g., cohort or case-control studies) have been performed, drawing on the strengths of techniques such as meta-regression to assist in the control of confounding. Meta-analyses already have provided important insights into important topics in medicine, such as the influence of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease (6).
The past two decades have seen enormous growth in the use of epidemiologic methods as a central part of the research armamentarium that is used to address critical questions and problems in renal medicine. Large, early, and highly influential initiatives such as the US Renal Data System have greatly catalyzed the growth of high-quality clinical research that is common today throughout the published nephrology literature. By acquiring and refining their understanding of these research methods, practicing nephrologists will improve their ability to appraise critically and to interpret the clinical studies that appear on a regular basis in CJASN. This research methods series will provide readers a solid understanding of the key clinical research designs and their strengths, weaknesses, and most important uses, all critical to the ability to digest the vast array of clinical research findings.
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Footnotes
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Published online ahead of print. Publication date available at www.cjasn.org.
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References
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