Amber Luong, MD, PhD
Johnson & Johnson recently announced its acquisition of Acclarent for over $800 million. This acquisition and the recent survey for new CPT codes for the balloon sinus ostial dilation beg the question as to when should this technology be utilized.
The CLEAR study, CLinical Evaluation to confirm sAfety and efficacy of sinuplasty in the paRanasal sinuses, as its name implies, set out to evaluate balloon dilatation for the treatment of chronic rhinosinusitis. Before reviewing the data, it is hard not to acknowledge the significant conflict of interest for most of the CLEAR study’s authors, who have direct financial interests in the sponsoring company and its technology platform. Companies often sponsor large clinical studies; however, most studies do not have authors with such financial interest in the outcome of the study. Although this in of itself does not invalidate the study, these significant conflicts of interest force a higher level of scrutiny when reviewing the study.
The CLEAR study is a multicenter prospective observational study (not a prospective randomized clinical trial), whose results were published in a series of 3 articles representing different follow-up time points: 24 weeks, 1 year, and 2 years. The study divided the patients into 2 subgroups: those who underwent balloon dilatation alone and those that underwent both balloon and traditional endoscopic sinus surgery (referred to as the “hybrid procedure”). Although a reasonable type of study, observational studies have significant limitations. For one, the non-random assignment of patients to either the balloon dilatation or to both procedures creates a systematic bias. As the only criterion to assign whether the patient gets the balloon only or the hybrid procedure, the surgeon preference in this study marred with a significant conflict of interest creates a bias in favor of the balloon dilatation. Some critics would argue that the lack of an established criterion for using the balloon only technique with the existing conflict of interest along with the non-blinded analysis of the endoscopic exam should invalidate the study. Nonetheless, I think it is worth looking at the data.
Although there were 2 groups within the study (i.e., patients who had undergone balloon only dilatation and patients who received the hybrid procedure), only a paired t-test analysis before and after the surgical intervention was performed for each group independently. There was no comparison between groups because the study was not originally designed or controlled to compare these 2 groups. The temptation to perform such post-hoc analysis should be resisted as the protocol did not control for other variables that would allow a legitimate comparison. That being said, the study could have designed to control for confounders to allow for such a comparison.
In the CLEAR study, 109 subjects were originally enrolled, 59 who had undergone the “hybrid” procedure and 56 who had only undergone just the balloon dilatation. At the 2-year follow-up, the primary endpoint was SNOT-20 quality-of-life scores and changes in the Lund-MacKay score. The patency rates were not formally addressed and the authors referred back to the 1-year follow-up results on patency rates. Sixty-five patients were available at the 2-year follow-up: 34 “balloon-only” and 31 “hybrid” patients. The study reported a significant change from baseline in SNOT-20 scores and Lund-MacKay CT scores. Based on these results, the authors concluded that changes in SNOT-20 scores and CT scores were sustained for at least 2 years.
On initial evaluation of the data, the sustained improvement of the mean Lund-MacKay CT score over 2 years after intervention with the balloon-only technique appears clinically significant with a mean pre-op CT score of 5.67 as compared to a 1.75 mean post-op CT score with p=0.015. However, review of the reported confidence intervals show an overlap of the confidence intervals suggesting that the true mean CT scores may be the same (2.76–8.58 pre-op and 0.60–2.90 post-op). Consequently, one would have to conclude from these confidence intervals that a conclusion about the change in CT scores for the balloon-only patients is inconclusive. This is unlike the patients who had undergone the hybrid procedure where the confidence intervals for pre- and post-intervention do not overlap at all (9.97–14.13 and 1.36–5.14, respectively). Consequently, one can conclude a significant difference between pre- and the 2-year follow-up time period for CT scores in patients undergoing the hybrid procedure.
So, regardless of the conflict of interest and the other limitations associated with observational studies, the CLEAR study shows a statistically meaningful change in CT scores before and after with only the hybrid intervention and not with the balloon only intervention. Unfortunately a similar analysis could not be performed with the SNOT-20 scores because the confidence intervals were not reported.
In light of J&J’s acquisition of Acclarent, one must assume that J&J saw substantial value in Acclarent’s technology and business model. Of course, it is plausible that the company has other valuable intellectual property. Additional, unpublished data may be available, but that seems unlikely. Regardless, critical review of the published CLEAR data does not make a robust case in support of balloon dilatation alone. As a practicing otorhinolaryngologist, I can only evaluate new techniques and devices on the merits that they provide for treating my patients. From that perspective, I have yet to see the advantages of the balloon dilatation technique for routine use in the management of chronic rhinosinusitis.
That being said, I can envision a couple of clinical scenarios where the balloon technology may be quite useful. For example, we have used balloon dilatation for the management of frontal sinus ostia stenosis with some benefit. Another possible situation where balloon dilatation may be quite effective is for the management of complications from acute sinusitis. In revision CRS, lateralization of the middle turbinate causing obstruction of the frontal sinus outflow tract may also represent another clinical situation well suited for balloon dilatation. Furthermore, balloon dilatation may be suited for the management of sinusitis associated with barotrauma. Finally, it is possible that balloon techniques play a role in the management of subpopulations of patients with chronic rhinosinusitis, but the current data have done little to define those characteristics of those patients. A handful of studies are starting to emerge evaluating this technique for these scenarios, but clearly more studies are warranted.