They found deficiencies in many aspects. An important cause of the confusion is the lack of uniformity and transparency in terminology This is not surprising and occurs often when new methods are introduced. It is to be expected that the state of affairs will improve as these methods become more widespread.
National Center for Biotechnology Information , U. J Gen Intern Med. Published online Sep Nowacki , PhD. Amy S. Author information Article notes Copyright and License information Disclaimer.
Corresponding author. This article has been cited by other articles in PMC. Abstract Increasingly, the goal of many studies is to determine if new therapies have equivalent or noninferior efficacies to the ones currently in use. Type of study Null hypotheses Research hypothesis Traditional comparative There is no difference between the therapies There is a difference between the therapies Equivalence The therapies are not equivalent The new therapy is equivalent to current therapy Noninferiority The new therapy is inferior to the current therapy The new therapy is not inferior to the current therapy.
Open in a separate window. Figure 1. Figure 2. Table 2 Sample Size to Achieve 0. Equivalence margin Sample size a per group 0. Clear statement and justification of the equivalence margin. Acknowledgments Conflict of Interest None disclosed. References 1. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing equivalence of average bioavailability.
J Pharmacokin Biopharm. N Engl J Med. Wellek S. Testing Statistical Hypotheses of Equivalence. Garret AD. Therapeutic equivalence: fallacies and falsification. Statist Med. Kaul S, Diamond GA.
Good enough: a primer on the analysis and interpretation of noninferiority trials. Ann Intern Med. Am J Epidemiol. Hintze J. PASS Kaysville, Utah www.
Contact Us. About the author. Teuscher has been involved in clinical pharmacology and pharmacometrics work since He holds a PhD in Pharmaceutical Sciences from the University of Michigan and has held leadership roles at biotechnology companies, contract research organizations, and mid-sized pharmaceutical companies.
Prior to joining Certara, Dr. At Certara, Dr. Teuscher developed the software training department, led the software development of Phoenix, and now works as a pharmacometrics consultant. He specializes in developing fit-for-purpose models to support drug development efforts at all stages of clinical development.
He has worked in multiple therapeutic areas including immunology, oncology, metabolic disorders, neurology, pulmonary, and more. Teuscher is passionate about helping scientists leverage data to aid in establishing the safety and efficacy of therapeutics.
Recommended for you. Non-Inferiority Trial This is a trial with the primary objective of showing that the response to the investigational product is not clinically inferior to a comparative agent active or placebo control. Depending on our test hypothesis, efficacy could be showing that: The new drug is at least as good as the control It could be proving that the new drug is better than the control It could even be to confirm that the new drug is equivalent to the control Such hypotheses are widely referred to in publications and texts as non-inferiority trials , superiority trials and equivalence trials respectively.
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Overview What's New. Try Now. Only Among the subgroup of reports that fulfilled all of the requirements, Conducting a comprehensive critical review of mental health studies that have used an equivalence or noninferiority design is outside the scope of this paper.
As but one of numerous examples, Frueh et al. Thus, results were not optimal to support conclusions of equivalence between the two treatment conditions.
The studies contained explicit explanations of the methodology used, presented the necessary sample size parameters, and conducted appropriate analyses. One study evaluated a telephone administered cognitive behavior therapy for treatment of OCD in comparison to the face-to-face delivery Lovell et al.
Another study tested the noninferiority of telepsychiatry consultations and follow-up compared to those conducted in-person O'Reilly et al. A third study compared Repetitive Transcranial Magnetic Stimulation to Electroconvulsive Therapy for treatment of severe depression Eranti, et al. The fourth investigated the effectiveness of standard treatment of depression in primary care clinics with versus without antidepressant medication Hermens et al. It should be noted that even among these strong studies there were some weaknesses.
In some cases, the terms seemed to be used interchangeably. Also, in the choice of an active control treatment, some studies did not clearly establish that the standard treatment had previously been well validated as effective. Consistent documentation of obtained power was not always provided either. With the ongoing development of new approaches to administering standard treatments, noninferiority and equivalence designs will continue to become more common in mental health research.
The increasing utilization of these designs to expand access to evidence based treatment of traumatic stress necessitates improved understanding of the methodological challenges and issues.
It is important for both researchers and consumers of research to be aware of how these designs are implemented and what conclusions may be appropriately drawn from findings. As a researcher, one must pay careful attention to methodological rigor including choice of active control, noninferiority margin, trial conduct, and analytic methods. The study methods must be pre-determined through a systematic process of decision making and analysis.
As a consumer of research, it is important to assess the accuracy of claims of noninferiority or equivalence. All views and opinions expressed herein are those of the authors and do not necessarily reflect those of our respective institutions or the Department of Veterans Affairs. We acknowledge the valuable comments provided by Rebecca G. Knapp on an earlier draft of this essay.
National Center for Biotechnology Information , U. J Trauma Stress. Author manuscript; available in PMC Oct 1. Carolyn J. Greene , 1 Leslie A.
Morland , 1 Valerie L. Durkalski , 2 and B. Christopher Frueh 3. Leslie A. Valerie L. Christopher Frueh. Author information Copyright and License information Disclaimer.
Copyright notice. The publisher's final edited version of this article is available at J Trauma Stress. See other articles in PMC that cite the published article. Open in a separate window. Figure 1. Importance to Mental Health Research Within recent years, there has been a significant increase in the number of effective, well validated treatments for individuals suffering from traumatic stress disorders.
Key Methodological Issues The methodological challenges in conducting a noninferiority study are significant; especially since poor trial design and execution can erroneously suggest a similarity.
Use of the Noninferiority and Equivalence Designs in Published Studies Noninferiority conclusions are frequently drawn in studies that did not properly utilize an appropriate design. Conclusions With the ongoing development of new approaches to administering standard treatments, noninferiority and equivalence designs will continue to become more common in mental health research. References Blackwelder WC. Current issues in clinical equivalence trials.
Journal of Dental Research. Controlled Clinical Trials. A comparison of intent-to-treat and per-protocol results in antibiotic non-inferiority trials. Statistics in Medicine. Scientific and ethical issues in equivalence trials. Journal of the American Medical Association. Planning and monitoring of equivalence studies.
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