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effective dose. The authors admitted that the rapid cross over may well have resulted from patient and clinician bias. We wonder what information about the study rationale and possible outcomes was offered to potential enrollees, and why such a short period was allowed. It appears that the follow-up calls came from the treating institution, rather than independent observers, which adds potential bias. More important, the lack of a meaningful control group means that no one can claim that the apparent benefit was greater than a placebo effect, which is strong in surgical and other interventional studies.4 With others,2,5 we remain convinced of the need for a major study comparing cholecystectomy with a sham treatment, which, at the same time, will assess the predictive value of dynamic biliary scanning, another controversial topic. After detailed discussion with a bioethicist, and encouragement from formal discussions with a family advocacy group, we have detailed plans for such a study. We have received preliminary agreements to participate from gastroenterology and surgical partners in more than a dozen institutions, and are awaiting funding decisions on a planning grant. REFERENCES 1. Bielefeldt K. The rising tide of cholecystectomy for biliary dyskinesia. Aliment Pharmacol Ther 2013;37:98e106. 2. Bielefeldt K, Saligram S, Zickmund SL, et al. Cholecystectomy for biliary dyskinesia: how did we get there? Dig Dis Sci 2014; 59:2850e2863. 3. Richmond BK, Grodman C, Walker J, et al. Pilot Randomized Controlled Trial of Laparoscopic Cholecystectomy vs Active Nonoperative Therapy for the Treatment of Biliary Dyskinesia. J Am Coll Surg 2016;222:1156e1163. 4. Cotton PB, Durkalski V, Romagnuolo J, et al. A multicenter, randomized trial of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction in patients with pain after cholecystectomy e the EPISOD trial. JAMA 2014;311:2101e2109. 5. Gurusamy KS, Junnarkar S, Farouk M, Davidson BR. Cholecystectomy for suspected gallbladder dyskinesia. Cochrane Database Syst Rev 2009;:CD007086.
Disclosure Information: Nothing to disclose.
A Large Prospective Cohort Study In reply to Cotton and colleagues Bryan K Richmond, Charleston, WV
MD, MBA, FACS
We read with interest the comments made by Dr Cotton and his associates and are grateful for the opportunity to
reply. Dr Cotton has asked several probing questions of our study, which we agree are both important and relevant. Our study was a pilot designed to investigate not only the results of surgery compared with a medical therapy, but also, and not insignificantly, to establish whether or not a randomized controlled trial exploring this topic was even feasible. During the initial protocol development, we planned to titrate the dosage of amitriptyline in the nonoperative arm, and to not allow cross over to the surgically treated group until after 3 months of nonoperative therapy had failed. When this was discussed with prospective enrollees, we concluded that this was not feasible. The bias toward surgery from both patient and referral sources was too high, and patients were simply not willing to “wait it out.” Also, despite references to the potential benefit of amitriptyline in this setting, the fact remains that there is no “gold standard” medical therapy to offer to a nonoperative study arm. Therefore, we allowed early crossover, and anticipated that it would occur, which it certainly did. Although this was suboptimal from the standpoint of a randomized trial evaluating the role and efficacy of amitriptyline in treating biliary dyskinesia, it did allow establishment of a prospective cohort of 26 surgically treated patients, all of whom met standardized criteria for enrollment (that of functional gallbladder disorder as defined by the Rome III criteria, a CCK-HIDA scan using accepted and current Society of Nuclear Medicine protocols), and all of whom had standardized preoperative and postoperative quality-of-life assessments for validation of improvement. This had been missing from the surgical literature, and we believe this is a welcome addition in that regard. The idea of a sham trial is interesting, and would certainly provide the strongest and highest quality evidence as to the role of surgery in treating biliary dyskinesia. In fact, our institution, the West Virginia University/Charleston Division, was one of the institutions that corresponded with Dr Cotton during the preliminary phases of his protocol development, and we are not averse to participating in subsequent trials. However, for the reasons mentioned in our article, specifically, those relating to the cost of such a study, potential ethical concerns, and what we predict will be very difficult accrual process, we stand by our conclusion that a large prospective cohort study may well be the best method by which to study this complex and interesting problem. Disclosure Information: Nothing to disclose.