Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
Journal website http://www.jocmr.org

Review

Volume 8, Number 5, May 2016, pages 361-366


Unresolved or Contradictory Issues About Management of Patients With Patent Foramen Ovale and Previous Cryptogenic Stroke: Additional Randomized Controlled Trials Are Eagerly Awaited

Figure

Figure 1.
Figure 1. PFO occluding devices. (a) Gore Helex septal occluder; (b) STARFlex PFO implant device; (c) Amplatzer PFO occluder.

Tables

Table 1. Strengths and Limitations of Meta-Analyses of PFO Closure RCTs for Stroke Recurrence
 
StudyRCTs onlyITT subset onlyRandom effect statistical modelAnalysis of potential adverse eventsConclusion beneficial
ITT: intention-to-treat; RCT: randomized controlled trial.
Ntaios et al [4]YesNoNoYesNo overall; yes with Amplatzer
Pineda et al [5]YesNoYesYesNo overall; yes as treated
Kitsios et al [6]YesNoYesNoInconclusive
Riaz et al [7]YesNoYesYesNo overall; yes as treated
Hakeem et al [8]YesNoYesYesProbably
Kwong et al [9]YesYesYesYesNo
Nagaraja et al [10]YesYesYesYesNo
Rengifo-Moreno et al [11]YesNoNoYesYes
Khan et al [12]YesNoNoYesYes
Spencer et al [13]YesNoYesYesNo
Wolfrum et al [14]NoNoYesYesNo
Capodanno et al [15]NoYesYesYesNo overall; yes with Amplatzer
Pandit et al [16]YesYesNoNoNo overall; yes with Amplatzer
Udell et al [17]YesYesYesYesNo
Li et al [18]YesYesYesYesNo

 

Table 2. Approaches Used for Assessing a Randomized Controlled Trial: “Intention to Treat”, “As Treated” and “Per Protocol”
 
Intention to treatRandomized clinical trials analyzed by the “intention to treat” (ITT) approach provide unbiased comparisons among the treatment groups. “Intention to treat” analyses are done to avoid the effects of crossover and dropout, which may break the random assignment to the treatment groups in a study. ITT analysis provides information about the potential effects of treatment policy rather than on the potential effects of specific treatment. Since it started in the 1960s, the principle of ITT has become widely accepted for the analysis of controlled clinical trials. However, full application of ITT analysis can only be performed where there are complete outcome data for all randomized subjects.
As treated“As treated” analysis has the general idea of comparing the subjects with the treatment regimen that they received. It does not consider which treatment they were assigned for the treatment.
Per protocolThe “per protocol” analysis, also known as an “on-treatment” analysis, can only be restricted to the participants who fulfill the protocol in the terms of the eligibility, interventions, and outcome assessment. Indeed, the “per protocol” analysis restricts the comparison of the treatments to the ideal patients, that is, those who adhered perfectly to the clinical trial instructions as stipulated in the protocol. However, by restricting the analysis to a selected patient population, it does not show the practical value of the drug or method that has to be tested.