Issues with Statistical Risks for Testing Methods in Noninferiority Trial Without a Placebo ARM

Hm, Hung; Sj, Wang; O’Neill, Robert T.

doi:10.1080/10543400601177343

Cited by 34 publications

(44 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When people believe that a modality will work better, they feel better [25][26][27]. In many of the LLLT studies, there were either no control groups or the studies were poorly conducted [16].…”

Section: Discussionmentioning

confidence: 99%

The effects of low-level laser therapy in patients with wrist pain: is this Mickey Mouse science?

Petrofsky

Chung

Fazio

et al. 2014

PTRS

View full text Add to dashboard Cite

Objective: Low level laser treatment (LLLT) is widely used in physical therapy practice. It is combined with physical therapy or LLLT alone. The purpose of this study is to evaluate the effectiveness of LLLT on patients' perception of general wrist pain. Design: Longitudinal study. Methods: Forty-eight subjects with wrist pain who were in the age range of 18-70 years old were examined. The subjects were asked, via an interview and a visual analog scale, to grade their wrist pain. They were asked to rotate their wrists through full range of motion and the angle at which any pain occurred was assessed. Each subject was then exposed to one of the following: 1) treatment with an infrared laser with the power turned off (placebo), 2) treatment with an infrared therapeutic laser, 3) treatment with a red therapeutic laser, 4) treatment with an ultraviolet laser, 5) treatment with a blue laser, 6) treatment with a Mickey Mouse flashlight. The duration of the treatment was 3 sessions in 3 days. Results:The results of the experiments showed that while pain was reduced both immediately after and the next day after laser therapy (p<0.05), there was no significant difference between the laser groups and the placebo group. However, the Mickey Mouse flashlight treatment groups had a greater range of motion than the laser groups (p<0.05). Conclusions: While pain was reduced in all laser groups, it was probably a placebo effect. The Mickey Mouse flashlight group probably received benefit from the heat of the flashlight.

show abstract

Section: Discussionmentioning

confidence: 99%

The effects of low-level laser therapy in patients with wrist pain: is this Mickey Mouse science?

Petrofsky

Chung

Fazio

et al. 2014

PTRS

View full text Add to dashboard Cite

show abstract

“…There are many issues and controversies surrounding this second type of non-inferiority trials (Carroll 2013, D'Agostino et al 2003, Fleming 2008, 2007, 2013, Kang and Tsong 2010, Sanchez and Chen 2006, U.S. FDA 2010. One of these issues is which type I error rate should be evaluated and controlled under the nominal level (Hung et al, 2007, Kang and Tsong 2010.…”

Section: Introductionmentioning

confidence: 98%

“…One of these issues is which type I error rate should be evaluated and controlled under the nominal level (Hung et al, 2007, Kang and Tsong 2010. According to existing research, there are three kinds of type I error rates available in non-inferiority trials (Hung et al, 2007, Kang and Tsong 2010.…”

Section: Introductionmentioning

confidence: 99%

“…(4) The within-trial type I error rate represents the type I error rate of falsely concluding noninferiority in (1) with the constant margin when the non-inferiority trial is repeated infinitely many times with the same constant margin (Hung et al 2007). It seems that the within-trial type I error rate is the most familiar type I error rate to statisticians and clinicians in clinical trials.…”

mentioning

confidence: 98%

“…(7) Hung et al (2007) refer to the within-trial type I error rate as the conditional type I error rate, but this is quite confusing terminology. When the within-trial type I error rate is evaluated, it is "unconditional" probability, not "conditional" probability, because the non-inferiority margin is treated as a constant.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Avoiding ambiguity with the Type I error rate in noninferiority trials

Kang

2015

Journal of Biopharmaceutical Statistics

View full text Add to dashboard Cite

This review article sets out to examine the Type I error rates used in noninferiority trials. Most papers regarding noninferiority trials only state Type I error rate without mentioning clearly which Type I error rate is evaluated. Therefore, the Type I error rate in one paper is often different from the Type I error rate in another paper, which can confuse readers and makes it difficult to understand papers. Which Type I error rate should be evaluated is related directly to which paradigm is employed in the analysis of noninferiority trial, and to how the historical data are treated. This article reviews the characteristics of the within-trial Type I error rate and the unconditional across-trial Type I error rate which have frequently been examined in noninferiority trials. The conditional across-trial Type I error rate is also briefly discussed. In noninferiority trials comparing a new treatment with an active control without a placebo arm, it is argued that the within-trial Type I error rate should be controlled in order to obtain approval of the new treatment from the regulatory agencies. I hope that this article can help readers understand the difference between two paradigms employed in noninferiority trials.

show abstract

Challenges and regulatory experiences with non‐inferiority trial design without placebo arm

2009

Self Cite

View full text Add to dashboard Cite

For a non-inferiority trial without a placebo arm, the direct comparison between the test treatment and the selected positive control is in principle the only basis for statistical inference. Therefore, evaluating the test treatment relative to the non-existent placebo presents extreme challenges and requires some kind of bridging from the past to the present with no current placebo data. For such inference based partly on an indirect bridging manipulation, fixed margin method and synthesis method are the two widely discussed methods in the recent literature. There are major differences in statistical inference paradigm between the two methods. The fixed margin method employs the historical data that assess the performances of the active control versus a placebo to guide the selection of the non-inferiority margin. Such guidance is not part of the ultimate statistical inference in the non-inferiority trial. In contrast, the synthesis method connects the historical data to the non-inferiority trial data for making broader inferences relating the test treatment to the non-existent current placebo. On the other hand, the type I error rate associated with the direct comparison between the test treatment and the active control cannot shed any light on the appropriateness of the indirect inference for faring the test treatment against the non-existent placebo. This work explores an approach for assessing the impact of potential bias due to violation of a key statistical assumption to guide determination of the non-inferiority margin.

show abstract

Issues with Statistical Risks for Testing Methods in Noninferiority Trial Without a Placebo ARM

Cited by 34 publications

References 38 publications

The effects of low-level laser therapy in patients with wrist pain: is this Mickey Mouse science?

The effects of low-level laser therapy in patients with wrist pain: is this Mickey Mouse science?

Avoiding ambiguity with the Type I error rate in noninferiority trials

Challenges and regulatory experiences with non‐inferiority trial design without placebo arm

Contact Info

Product

Resources

About