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Articles: Dino Vaira, Nimish Vakil, Marcello Menegatti, Ben van't Hoff, Chiara Ricci, Luigi Gatta, Giovanni Gasbarrini, Mario Quina, Jose M. Pajares Garcia, Arie van der Ende, Rene van der Hulst, Marcello Anti, Cristina Duarte, Javier P. Gisbert, Mario Miglioli, and Guido Tytgat The Stool Antigen Test for Detection of Helicobacter pylori after Eradication Therapy Ann Intern Med 2002; 136: 280-287 [Abstract] [Full text] [PDF]

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Sequential therapy: Minimizing risk and maximizing outcome

Dino Vaira, Angelo Zullo, Nimish Vakil   (7 May 2007)

Sequential therapy: Minimizing risk and maximizing outcome 7 May 2007
Dino Vaira, Associate Professor of Internal Medicine Department of Internal Medicine & Gastroenterology, Angelo Zullo, Nimish Vakil Send rapid response to journal: Re: Sequential therapy: Minimizing risk and maximizing outcome vairadin{at}med.unibo.it Dino Vaira, et al.	There are several misstatements in the letter which we will address first: (a) there was no sponsor for our study; (b) triple therapy is a ¡§legacy¡¨ therapy solely in a fantasy world. Triple therapy was recently reaffirmed by an International Consensus Group as the principal therapy to be used worldwide and by US and Japanese guidelines. (1-3) It is therefore an appropriate control group for any new therapy. Our study began in 2003 when it was uncertain whether sequential therapy was truly effective in large cohorts. A fundamental question remained unanswered until now- Was sequential therapy the answer to Clarithromycin resistance? An expert International Consensus group reviewed the data on sequential therapy in 2005 and concluded that it was promising but more data were needed, particularly with regard to clarithromycin resistance. (1) As there were no safety issues with either treatments in our study and as the international community of experts felt that more data were needed, it was imperative that we continue the trial. We have already demonstrated that a triple therapy with levofloxacin is an effective salvage therapy for patients who fail sequential therapy. (4) Therefore, a perfectly satisfactory alternative therapy of proven efficacy was available for failures. Data on failures will be reported elsewhere. Ethical trial designs minimize risk to patients and maximize the likelihood of a meaningful outcome for patients and society. Early termination of a trial requires the demonstration of a serious unanticipated side-effect or an unanticipated difference between treatments that is much larger than expected. (5) Individuals taking a decision to terminate a trial early have a heavy responsibility to both those who have taken part in the trial already and to society. (5) The results of our study were within the anticipated treatment estimates and there were no safety issues, therefore our responsibility to the patients who volunteered, to society, and to the scientific community was to continue. The suggestion that we not have a control group is inappropriate. The limitations of uncontrolled studies are well known to all serious researchers. Underpowered, uncontrolled trials continue to be published, sometimes with unsafe agents, These studies yield biased results with wide confidence intervals that mislead rather than illuminate, and place patients at risk of drug toxicity and resistant organisms. These should be deplored rather than encouraged. The benefits of our study to individual patients and to society in general should be obvious to impartial observers. Dino Vaira MD Dept of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy; Angelo Zullo MD Gastroenterology Unit, ¡§Nuovo Regina Margherita Hospital¡¨, Rome, Italy; Nimish Vakil MD University of Wisconsin School of Medicine and Public Health, Madison WI, USA and Marquette University College of Health Sciences, Milwaukee WI, USA References: 1. Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El Omar E, Graham DY, et al. Current concepts in the management of Helicobacter pylori infection ƒ{ The Maastricht III Consensus Report. Gut 2006 Dec 14; [Epub ahead of print]. 2. Fujioka T, Yoshiiwa A, Okimoto T, Kodama M, Murakami K. Related Articles, Guidelines for the management of Helicobacter pylori infection in Japan: current status and future prospects. J Gastroenterol. 2007;42 Suppl 17:3-6. 3. Chey WD, Wong BCY. American College of Gastroenterology guideline for H pylori infection. Am J Gastroenterol 2007, in press. 4. Gatta L, Zullo A, Perna F, Ricci C, De Francesco V, Tampieri A, Bernabucci V, Cavina, M, Hassan C, Ierardi E, Morini S, Vaira D. A 10 days levofloxacin base triple therapy in patients who failed two eradication courses. Alimentary Pharmacology Therapeutics 2005; 22: 45-49. 5. Grant A. Stopping clinical trials early. BMJ 2004;329:525-6. Conflict of Interest: They have been decalred in the paper and have not been changed since