Course:PHAR506/noninferiority
| Session Title | |
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| PHAR 506 | |
| Section: | |
| Instructor: | Dr. Peter Loewen |
| Email: | peter.loewen@ubc.ca |
| Office: | |
| Office Hours: | |
| Class Schedule: | |
| Classroom: | PHRM 3101 |
| Important Course Pages | |
| Syllabus | |
| Lecture Notes | |
| Assignments | |
| Course Discussion | |
Understanding & Interpreting Non-Inferiority Trials
Preparation for the P506 (17NOV15) & P535B (4FEB16) sessions
- Read the AMPLIFY trial
- Read How to Use a Noninferiority Trial
- Read Scientific and Ethical Issues in Equivalence Trials-JAMA
- Read the 2012 CONSORT-Noninferiority extension
- if you feel like you've got this all figured out, read EXAMINE
By the end of the session, upon study and reflection, students should be able to
- Name scenarios where non-inferiority trials are preferred over superiority trials, and scenarios where they are not.
- Explain what an MCID/non-inferiority margin is and roughly how they are determined, especially the "setting the margin" and "imputed placebo" approaches.
- Graphically depict the non-inferiority assumptions and the primary endpoint result for a clinical trial in terms of whether the intervention is non-inferior or not.
- Explain the role of ITT analysis vs. on-treatment analysis in superiority vs. non-inferiority trials.
- Describe the difference between superiority and non-inferiority trials in terms of what it means to be "conservative" and in terms of Type 1 and Type II errors.
- Be able to calculate the confidence intervals around any non-significant trial endpoint and personally evaluate it from the viewpoint of non-inferiority. Use my stats calculator for this.
- ADVANCED: Explain what a p-value on a non-inferiority finding means.
- ADVANCED: Think about the methodologic, practical, and ethical issues in TECOS and EXAMINE
Required Prior Knowledge & Skills
Self-test that you can do these things before showing up for the session, because NI trial design/interpretation is a special case of these concepts.
- be able to accurately explain what a p-value is
- be able to state what the usual null and alternative hypotheses are in a superiority trial
- be able to explain what it means to make a Type I and Type II error both in lay-language, and in terms of the null & alternative hypotheses
- explain why ITT analysis is the gold-standard approach in superiority RCTs
During the Sessions
PHAR 506 - NOVEMBER 2015 We'll discuss the foundational concepts behind NI trials in terms of
- practical clinical considerations
- ethical appropriateness
- statistical considerations
- We’ll do roundtable discussion using roughly a CONSORT-NI approach, so please come prepared to discuss the assigned trial. We will concentrate on the issues unique to NI trial design and interpretation.
PHAR 535B - FEBRUARY 2016
- We’ll do roundtable discussion using roughly a CONSORT-NI approach, so please come prepared to discuss the assigned trial. We will concentrate on the issues unique to NI trial design and interpretation.
- Bring vexing and/or interesting issues and questions for discussion.
Common Misconceptions and Sticking Points
- how does the definition of conservative differ in a NI trial from a superiority trial?
- precisely why (practically and philosophically) is the on-treatment (non-ITT) analysis so important in an NI trial?
- what does it mean to report a "p-value for non-inferiority"
Supportive Literature & Further Reading
- 7 questions to ask when evaluating a noninferiority trial. J Fam Pract 2014;63:E4–8.
- Noninferiority hypotheses and choice of noninferiority margin. Statist Med 2008;27:5392–406
- Similar The Same or Just Not Different-CJC
- Wangge G, et al. Regulatory scientific advice on non-inferiority drug trials. PLoS ONE 2013;8:e74818.
- The challenges of determining noninferiority margins: a case study of noninferiority randomized controlled trials of novel oral anticoagulants.
- Good Enough: A Primer on the Analysis and Interpretation of Noninferiority Trials-AIM
- Non-inferiority trials are unethical because they disregard patients’ interests-Lancet
- Trend Toward Noninferiority Trials May Mean More Difficult Interpretation of Trial Results-JNCI
- US FDA Guidance for Industry, Non-Inferiority Clinical Trials
- Health Canada Guidance for Industry re: Non-inferiority designs
- Guideline on the choice of non-inferiority margin-EMA
- Equivalence and noninferiority trials – are they viable alternatives for registration of new drugs?
- Quality of reporting of clinical non-inferiority and equivalence randomised trials - update and extension
- other classic NI trials for self-study and skill testing