prevention of post endoscopic retrograde cholangiopancreatography pancreatitis

Prevention of Post-EndCholangiopancreatog

A Cost-effective

David Nicols-Prez, PhD,* Ivn Castilla-RodrguRafael Romero-Garca, MD,* Venancio Nez-

Objectives: The aim of the present study was to perform a comparativecost-effectiveness analysis of the different strategies used to prevent postendoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis.Methods: We performed a cost-effectiveness decision analysis of 4prophylactic strategies (nonsteroidal anti-inflammatory drugs or NSAIDs,pancreatic stent, stent plus rectal indomethacin, and no prophylaxis) in asimulated cohort of 300 patients during 1 year. Treatment effectivenesswas defined as the number of patients who did not develop post-ERCPpancreatitis.Results: The baseline costs of each strategy were as follows: rectalNSAID $359,098, pancreatic stent $426,504, stent plus rectal indometha-

ORIGINAL ARTICLEvent PEP. The objective of this study was to perform a compara-tive analysis of cost-effectiveness between the different strategies.

MATERIALS AND METHODS

General Structure of the ModelTo assess financial costs, we used a decision tree model to

Specific author contributions: D.N.P. contributed to the conception and designof the study; generation, collection, assembly, analysis, and interpretation ofdata; and drafting and revision of the article. I.V.R. contributed to theanalysis and interpretation of data and the drafting and revision of thearticle. A.Z.G.G., R.R.G., and V.N.D. contributed to the acquisition of dataand revision of the article. E.Q.C. contributed to the drafting and criticalrevision of the article.

All authors approved the final version of the article, including theauthorship list.Guarantor of the article: Dr David Nicols-Prez.ated with complications and additional costs,11 and the optimalclinical context in which it should be applied has not been estab-lished. We hypothesized that there are marked differences in termsof cost-effectiveness between the strategies recommended to pre-

(email: [email protected]); and Enrique Quintero, PhD,Department of Gastroenterology, Hospital Universitario de Canarias,Ofra s/n, 38320 La Laguna, Tenerife, Spain (email: [email protected]).

The authors declare no conflict of interest.cin $479,153, and no prophylaxis $491,275. The mean number of casesdeveloping post-ERCP pancreatitis was 16, 21, 23, and 37 for the strate-gies rectal NSAID, pancreatic stent, stent plus rectal indomethacin, andno prophylaxis, respectively. Taking rectal NSAID prophylaxis as thereference strategy, the odds ratio of an episode of post-ERCP acute pan-creatitis after pancreatic stent placement was 1.33 (95% confidence in-terval [CI], 0.682.61); after stent plus indomethacin, it was 1.40 (95%CI, 0.722.73), and after no prophylaxis, it was 2.49 (95% CI, 1.354.59).Conclusions: Rectal NSAID administration proved to be the most cost-effective prophylactic strategy used to prevent post-ERCP pancreatitis. Thestrategy of no prophylaxis for this complication should be avoided.

Key Words: ERCP, pancreatitis, NSAIDs, stents, cost-effectiveness

(Pancreas 2014;00: 0000)

From the *Servicio de Aparato Digestivo, Hospital Universitario de Canarias,La Laguna, Tenerife; Canary Islands Foundation for Health and Research(FUNCIS), Santa Cruz de Tenerife; Health Services Research on Chronic Pa-tients Network (REDISSEC); Center for Biomedical Research of the CanaryIslands (CIBICAN), Santa Cruz de Tenerife; Departamento de MedicinaInterna, Universidad de La Laguna, Santa Cruz de Tenerife; and Institute ofBiomedical Technologies and Center of Biomedical Research of the CanaryIslands (CIBICAN), La Laguna University, Tenerife, Spain.Received for publication November 10, 2013; accepted June 27, 2014.Reprints: David Nicols-Prez, PhD, Department of Gastroenterology, Hospital

Universitario de Canarias, Ofra s/n, 38320 La Laguna, Tenerife, SpainSupplemental digital contents are available for this article. Direct URL citationsappear in the printed text and are provided in the HTML and PDF versionsof this article on the journal's Web site (www.pancreasjournal.com).

Copyright 2014 by Lippincott Williams & Wilkins

Pancreas Volume 00, Number 00, Month 2014

Copyright Lippincott Williams & Wilkins. Unauthoscopic Retrograderaphy Pancreatitis

ness Analysis

ez, PhD, Antonio Z Gimeno-Garca, PhD,*Daz, MD,* and Enrique Quintero, PhD*

O f all the endoscopic diagnostic and therapeutic proceduresapplied in gastroenterology, endoscopic retrograde cholangio-pancreatography (ERCP) is probably associated with a greater inci-dence of complications than any other. Post-ERCP complicationsinclude acute pancreatitis, bleeding, cholangitis, cholecystitis, andperforation, with incidence rates ranging from 4% to 16% and as-sociated mortality of 1%.1

The most common complication is acute pancreatitis with anincidence of up to 15%.1 The mechanisms underlying post-ERCPacute pancreatitis (PEP) are not well known, but the following havebeen proposed as possible pathogenetic factors: mechanical or ther-mal trauma of themajor duodenal papilla, high hydrostatic pressuresecondary to contrast injection, and the activation of pancreatic en-zymeswith the release of proinflammatory cytokines due to bacterialinfection.2 In addition, various patient-dependent or endoscopy-dependent risk factors for the development of PEP have been iden-tified.3 The former include younger age, female sex, a history ofPEP, sphincter of Oddi dysfunction, or the presence of a nondilatedbile duct. The latter include difficult cannulation, the number of in-jections of contrast medium into the main pancreatic duct, use of aprecut, pancreatic sphincterotomy, or biliary sphincteroplasty.4,5

Various strategies have been used to reduce the incidence ofacute pancreatitis, specifically pharmacological and endoscopicmethods.6 Numerous drugs have been used for the prophylaxis ofPEP, including nonsteroidal anti-inflammatory drugs (NSAIDs), ni-troglycerin, ceftazidime, somatostatin, octreotide, and protease in-hibitors. According to a recent European consensus report,7 the drugscurrently recommended for the prevention of PEP are NSAIDs(indomethacin and diclofenac). Twometa-analyses have confirmedthat these NSAIDs are beneficial in the prevention of PEP, al-though these analyses have been criticized for the low number ofstudies included, heterogeneity in the definition of PEP, and a sam-ple size of less than 200 patients in 2 of the studies analyzed.8,9 Re-garding endoscopic methods, only pancreatic stenting has beenshown to reduce the incidence of PEP and avoid severe pancreati-tis, according to the results of prospective and retrospective case-control studies and a meta-analysis.10 Although pancreatic stentingmay be clinically beneficial, this endoscopic procedure is associ-compare 4 strategies used for the prevention of PEP in a simulatedcohort of patients aged 50 years and older undergoing ERCP;these are as follows: (1) treatment with 100 mg rectal diclofenac

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Nicols-Prez et al Pancreas Volume 00, Number 00, Month 2014or indomethacin, (2) plastic pancreatic stent placement, (3) pan-creatic stent plus rectal indomethacin (100 mg), and (4) no pro-phylaxis. We chose the age 50 years and older because the meanage of patients enrolled in several clinical trials and cohort studiesis around 50 years of age.5,1217 The study setting was the gastro-enterology department of a tertiary referral hospital, where approx-imately 300 ERCPs are performed annually. Time horizon for themodel was 1 year, and only direct health care costs from the per-spective of the National Health Service were considered. Patientswith any of the following risk factors were defined as being at highrisk of PEP: history of PEP, sphincter of Oddi dysfunction, use ofa precut, pancreatic sphincterotomy, biliary sphincteroplasty with-out sphincterotomy, or repeated unsuccessful attempts at biliary orampullectomy cannulation. Patients with 2 or more of the follow-ing conditions were also considered to be at high risk: female sex,history of recurrent pancreatitis, repeated contrast injection in themain pancreatic duct, pancreatic acinarization, or pancreatic cytol-ogy.13 The severity of acute pancreatitis was rated according to thecriteria of Cotton et al,18 and PEPwas defined as abdominal pain inconjunction with serum amylase levels more than 3 times the upperlimit of normality measured 6 to 24 hours after ERCP. Post-ERCPacute pancreatitis was classified as mild, moderate, or severe if thepatient required hospitalization for less than 4 days, between 4 and10 days, and more than 10 days or presence of complications, indi-cation for surgery or death, respectively.

The probability of different clinical events occurring dur-ing ERCP was calculated on the basis of data obtained frompublished studies (Table 1, Supplemental Digital Content, athttp://links.lww.com/MPA/A334). Estimates of the costs associ-ated with each ERCP event were based on those published inthe Official Gazette of the Canary Islands (Table 2, SupplementalDigital Content, at http://links.lww.com/MPA/A334). These costswere expressed in 2014 US dollars using a conversion rate of1 is equal to $1.38.

For the decision tree analysis, the following assumptionswere made: (1) all pancreatic stents were inserted by experiencedendoscopists familiar with the technique; (2) for the baseline anal-ysis, the proportion of patients at high risk of PEP was 50%19; (3)there were no other complications directly related to pancreaticstent placement; (4) all stented patients underwent plain abdomi-nal x-ray to confirm spontaneous duodenal migration of the pan-creatic stent between the first and second week of placement; (5)in those cases with no evidence of spontaneous migration, endo-scopic stent removal was performed. In patients with severe PEP,gastroscopy was performed to rule out the presence of a pancre-atic stent, and (6) there was an average increase of hospital stayafter ERCP of 2, 7, and 10 days for patients with mild, moderate,and severe PEP, respectively. For patients with severe PEP who re-covered, we added the cost of 10 days stay in the intensive careunit.20 For patients with severe PEP who died, estimated intensivecare unit stay was 12 days,20 and (7) all deaths were due to episodesof severe PEP, not anesthetic-related, or other ERCP-related com-plications (such as bleeding or perforation).

Figure 1 shows the model and decision treewhere the 4 strat-egies for the prevention of PEP are compared. The strategiesNSAID and no prophylaxis distinguish between patients athigh and low risk for PEP. The decision tree for the strategy noprophylaxis (not shown for space reasons) was the same as that forNSAID. In patients who developed severe PEP, we distinguished be-tween recovery from PEP versus death due to PEP. The decision treefor the strategy stent (not shown for space reasons) was the sameas that for indomethacin plus stent. We added those branchesand their associated probabilities that included uncertainty associ-

ated with the technique of stent insertion and the possible compli-cations associated with the insertion technique or the prosthesis

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Copyright Lippincott Williams & Wilkins. Unauthoitself. Therefore, in addition to subdividing the patients accordingto high and low risk, we took into account the probabilities of suc-cessful and unsuccessful stent insertion, the probability of requiringgastroscopy in the absence of spontaneous duodenal migration ofthe pancreatic prosthesis, and the possibility of acute pancreatitisafter endoscopic stent removal.

Cost Analysis and Cost-effectiveness AnalysisWe performed a cost analysis and a 1-way sensitivity analy-

sis of all variables included in the model (Table 1 and 3, Supple-mental Digital Content, at http://links.lww.com/MPA/A334) totest its robustness and to identify scenarios that could alter the de-cision strategy. A cost-effectiveness analysis was then performed,with treatment effectiveness defined as the number of patientswho did not develop PEP. For patients who did not develop acutepancreatitis, the effectiveness of the strategy used was calculatedby multiplying the total number of patients in the cohort by the ex-pression (1 probability of pancreatitis). In the case of patientswho developed this complication, effectiveness was 0. The incre-mental cost-effectiveness ratio (ICER) was calculated using thefollowing formula:

ICER CostbCostaEffectivenessbEffectivenessa

where b is the option being compared, and a is the reference op-tion, with ICER being defined as the increase in average cost ofobtaining an additional unit of effectiveness on using b insteadof the option a. We also performed 2-way and 3-way sensitivityanalyses comparing variation in the incidence of acute pancreatitisin the dominant strategy (the least expensive and most effective)against the other strategies, taking into account variables such asthe percentage of patients at high risk of developing PEP or theincidence of PEP in stented patients.

Probabilistic Sensitivity AnalysisThe robustness of the model was tested with a probabilistic

sensitivity analysis using a Monte Carlo simulation. To performthis analysis, we specified the probability distribution functionsrepresenting the probability of each event, the duration of hos-pital stay, and the proportion of participants at high risk of PEP,according to data published in the literature (Table 3, Supple-mental Digital Content, at http://links.lww.com/MPA/A334). Cost-effectiveness results were calculated 10,000 times, taking randomvalues of these distributions each time. Results were plotted on acost-effectiveness plane. We used the TreeAge program (TreeAgeSoftware Inc, Williamstown, Mass) for the construction of thedecision tree, the performance of decision analysis, sensitivityanalysis, and Monte Carlo simulation. To estimate the risk ofPEP, odds ratio (OR), and 95% confidence intervals (CIs), weused SPSS v. 15 (Chicago, Ill). To estimate the range of deter-ministic sensitivity analysis of those parameters that only had asingle citation, we calculated the 95% CI for the mean of a bino-mial population using Epidat 3.1 statistical software (available athttp://dxsp.sergas.es).

RESULTS

Cost AnalysisAssuming a sample size of 300 patients per year and that

50% would be at high risk of developing PEP, the least expensivestrategy during the study period was rectal NSAID administra-

tion for the prevention of PEP, with an estimated annual cost of$359,098. In contrast, the strategy of no prophylaxis was the most

2014 Lippincott Williams & Wilkins

rized reproduction of this article is prohibited.

FIGURE 1. Decision tree model used to compare 4 prophylactic strategies for the prevention of PEP. The branch no prophylaxis has the samedesign as that for NSAID. The branch indomethacin plus stent has the same design as that for stent. Cases of acute pancreatitis afterpancreatic stent removal were classified as mild or moderate because there were no cases of severe acute pancreatitis in this subgroup.

Pancreas Volume 00, Number 00, Month 2014 Prevention of PEP: A Cost-effectiveness Analysis

2014 Lippincott Williams & Wilkins www.pancreasjournal.com 3

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

expensive with an annual cost of $491,275. The cost of the strat-egies plastic pancreatic stent insertion or stent plus rectal indo-methacin was $426,504 and $479,153, respectively (Table 1).

Cost-effectiveness AnalysisOn stratifying patients into high and low risk for PEP, we

observed that the strategy of rectal NSAID administration wasdominant over the other 3 strategies (Table 1), that is, the least ex-pensive and most effective strategy. We performed a sensitivityanalysis, assuming a rate of 4.7% acute pancreatitis, with a rangebetween 3.9% and 6.3%, according to previously published re-sults. In addition, outliers in the frequency of PEP (15%) wereconsidered to assess whether such an increase could lead to achange in the decision strategy. With these assumptions, the strat-egy based on rectal NSAIDs remained more cost-effective thanthe other 3 strategies. Given these results, we performed a 3-waysensitivity analysis comparing the rate of PEP with rectal NSAID,the rate of PEP with pancreatic stent, and the percentage of partic-ipants at high risk for PEP.When the percentage of patients at highrisk for PEP was 24%, rectal NSAID strategy proved more cost-

strategy (rectal NSAID) with the least protective strategy (no pro-phylaxis), it would be necessary to treat 14 patients to prevent 1case of PEP. The number of cases with severe PEP for each strat-egy was 1 (rectal NSAID), 1 (pancreatic stent), 2 (stent and rectalindomethacin), and 3 (no prophylaxis), with no statistically signif-icant differences between the strategies.

DISCUSSIONThe present study analyzed 4 PEP prevention strategies: phar-

macological prophylaxis, endoscopic prophylaxis, combined pro-phylaxis, and no prophylaxis. The results showed that the use ofrectal NSAID was the least costly and most effective strategy,whereas no prophylaxis was the most costly and least effectivestrategy. Rectal NSAIDs are inexpensive, simple to administer,and safe; no adverse effects have been reported in any of the trialspublished to date,1417 and in a randomized trial, the incidenceof bleeding was no greater than that observed with placebo.13

NSAIDs, however, may have a drawback in that they may fail toprotect against pancreatitis in patients with pancreatic duct ob-struction. In these cases, endoscopic intervention is necessary toensure drainage.

R o

rea

No prophylaxis 491,275 256

Nicols-Prez et al Pancreas Volume 00, Number 00, Month 2014Percentage = 70%NSAID 364,394 282Pancreatic stent 437,222 276Stent + indomethacin 510,978 273effective than the other strategies, as long as the probability ofPEP did not exceed 8%. Above 8%, pancreatic stent insertion wasmore cost-effective (Fig. 2). When the percentage of participantsat high risk for PEP was 50%, rectal NSAID strategy proved themost cost-effective, as long as the probability of PEP did not ex-ceed 8%. By contrast, pancreatic stenting was more effective andless expensive than rectal NSAID administration in high-risk pa-tients with a probability of PEP exceeding 8% (Fig. 2).

Probabilistic Sensitivity AnalysisFigure 3 shows cost and effectiveness results obtained from

10,000 Monte Carlo simulations for each alternative evaluated,with a mean 17, 21, 23, and 37 cases of PEP for the strategies rectalNSAID, stent, stent plus rectal indomethacin, and no prophylaxis,respectively. Taking rectal NSAID as the reference strategy, the riskof PEP (OR) after pancreatic stent insertion was 1.33 (95% CI,0.682.61); after stent plus rectal indomethacin, the risk (OR)was 1.40 (95% CI, 0.722.73), and for no prophylaxis, the risk(OR) was 2.49 (95% CI, 1.354.59). Comparing the dominant

TABLE 1. Comparison of Cost, Effectiveness,Mean Ratio, and ICERisk of Developing PEP

Cost, $Effectiveness

(Patients Without Panc

Percentage = 30%NSAID 353,803 284Pancreatic stent 415,788 281Stent + indomethacin 447,329 280No prophylaxis 458,389 263

Percentage = 50%NSAID 359,098 283Pancreatic stent 426,504 279Stent + indomethacin 479,153 277No prophylaxis 524,162 249


Copyright Lippincott Williams & Wilkins. UnauthoResults from the present study indicate that the use of a pan-creatic plastic stent is warranted in patients at high risk of PEP butshould not be used indiscriminately in all patients undergoingERCP. Das et al19 evaluated 3 strategies for the prevention of PEPand found that the use of stents in patients at high risk proved tobe a cost-effective strategy. According to our data, stenting seemsjustified in high-risk patients who will probably not benefit fromrectal NSAID prophylaxis (due to increased risk of pancreatic ductobstruction, as in pancreatic sphincterotomy or endoscopic papil-lectomy, or in patients with known hypersensitivity to NSAIDs).

The combined use of a stent and indomethacin prophylaxisis not a widespread strategy. It has, however, been evaluated re-cently in amulticenter clinical trial that compared rectal indometh-acin versus placebo in patients at high risk of PEP with pancreaticstenting performed at the discretion of the endoscopist. In thistrial, the use of rectal indomethacin in patients with or withouta stent significantly reduced the incidence of PEP.13 Our simula-tion data do not show that combination prophylaxis is superiorto NSAID or stent monoprophylaxis, and the cost-benefit analysis

f the 4 Strategies According to the Percentage of Patients at High

titis) Mean Ratio, $/Patient ICER PEP Rate

1246 0.0531479 Dominated 0.0631597 Dominated 0.0661742 Dominated 0.123

1269 0.0561528 Dominated 0.071730 Dominated 0.0761919 Dominated 0.146

1292 0.061584 Dominated 0.081871 Dominated 0.09

2105 Dominated 0.17



Pancreas Volume 00, Number 00, Month 2014 Prevention of PEP: A Cost-effectiveness Analysisby the authors of the aforementioned clinical trial noted that rectalindomethacin monoprophylaxis was more effective and economi-cally viable than stent insertion alone, stenting and rectal indo-methacin combined, or no prophylaxis. Furthermore, a recentmeta-analysis did not show that the combination of rectal indo-methacin and pancreatic stent was superior to either of these strat-egies alone.21

FIGURE 2. The figure shows a 3-way sensitivity analysis of the 4 strategierectal NSAIDs or pancreatic stent insertion and the proportion of patientsPEP, the strategy stent wasmore cost-effective than the strategy NSAID folow frequency of PEP after stent insertion. If the frequency of PEP after stenIn panel B, with 50% of patients at high-risk of PEP, similar results are shlower frequencies of PEP after stent insertion.


Copyright Lippincott Williams & Wilkins. UnauthAccording to published evidence from case-control studiesand clinical trials, the incidence of PEP in control participants ishigher than in those receiving rectal NSAID or pancreatic stentprophylaxis.22 In our simulation, the strategy of no prophylaxiswas not less costly or more cost-effective compared with theother strategies, and this hypothetical option is rarely seen in clin-ical practice or clinical trial reports. In situations of deficient

s according to the probability of PEP (PEP) after the administration ofat high-risk of PEP. In panel A, with 24%of patients at high-risk ofr a frequency of PEP in the NSAID group above 8%, accepting a veryt insertion increases, rectal NSAID prophylaxis is more cost-effective.own, although rectal NSAID prophylaxis is more cost-effective with

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pros mito

Nicols-Prez et al Pancreas Volume 00, Number 00, Month 2014technique in biliary cannulation and/or pancreatic stent insertion,suggesting little experience in ERCP, the strategy of no prophy-laxis may be preferable. Some studies addressing the risk of PEPhave shown mixed results regarding the influence of endoscopistexperience or the volume of procedures at hospitals where ERCPis performed.23 When performed by an endoscopist in the trainingphase, the risk of PEP is greater, and no prophylaxis may proveless expensive, but it would undoubtedly be more efficient to referthe patient to a center experienced in the technique of ERCP.

FIGURE3. Graph showing the cost and effectiveness of each of the 4trial runs). The administration of rectal NSAIDs as monoprophylaxis wathe least effective andmost costly. Costs are expressed in US dollars. EdThe cost-effectiveness analysis showed that in clinical prac-tice, the administration of rectal NSAIDs is more cost-effectiveand efficient than the other 3 strategies. Using Monte Carlo simu-lation, prophylaxis with rectal NSAIDs significantly decreasedthe overall number of episodes of PEP but failed to show a signif-icant reduction in the incidence of severe PEP. Our findings sup-port those of 2 meta-analyses showing the superiority of rectalNSAID in preventing PEP versus pancreatic stent insertion.8,21

The main strength of the present study is that it compares4 prophylactic strategies, including 3 active strategies and one ofno prophylaxis. Two of the active strategies are currently recom-mended for PEP, and the third, albeit not established, has beenused in a recent multicenter clinical trial that included patientsat high risk of PEP.13 In addition, the data used in the design ofthe decision analysis were derived from various clinical trialsand prospective case series, which help translate the findings toclinical practice.

The study has certain limitations. First, the estimated proba-bilities of PEP after rectal NSAID prophylaxis were derived fromrandomized clinical trials. Clinical trials using rectal diclofenacor indomethacin as monoprophylaxis are scarce; only 4 trialsused these NSAIDs at a dose of 100 mg,1417 whereas 2 othersused lower doses of rectal diclofenac (2550 mg)24 or intramus-cular diclofenac instead.25 In addition, we found no randomizedclinical trials comparing the efficacy of pancreatic stenting withrectal NSAID use. This paucity of data may limit the validity ofthe results obtained in the sensitivity analysis. Randomized clini-cal trials addressing the role of pancreatic stenting in high-riskpatients and in the average population are required. However,


Copyright Lippincott Williams & Wilkins. Unauthothese trials are difficult to conduct due to the inherent heterogene-ity of patients, endoscopists, and procedures. In addition, ethicalissues arise concerning the nonuse of stents in high-risk patientsin randomized clinical trials comparing pancreatic stenting ver-sus rectal NSAID use. Second, the model does not discriminatebetween different risk factors for PEP or combinations of suchrisk factors4 and therefore does not establish different probabili-ties of developing PEP according to the degree of risk. How-ever, in the analysis of deterministic and probabilistic sensitivity,

phylactic strategies, calculated usingMonte Carlo simulation (10,000ore cost-effective than the other 3 strategies. No prophylaxis wasr's note: A color image accompanies the online version of this article.

we used a range of probabilities of PEP consistent with differentrisks in accordance with previously published data. Finally, thedecision analysis did not include indirect costs.

Although the economic aspect is important in the devel-opment of a decision model, ethical considerations related to therisk of discarded alternatives should not be neglected. Thus,although the strategy based on the administration of rectal NSAIDsproved the most cost-effective, each case and its associated risk ofPEP should be studied to select the most appropriate prophylac-tic strategy. In a patient at high risk of PEP, prophylactic pancre-atic stenting may be preferable to rectal NSAID use, regardlessof cost considerations. Pancreatic stenting seems clearly justifiedin high-risk patients who will probably not benefit from rectalNSAID prophylaxis due to increased risk of pancreatic duct ob-struction, as in pancreatic sphincterotomy or endoscopic papil-lectomy, in patients with several concomitant risk factors forPEP (female sex, sphincter of Oddi dysfunction, difficult cannula-tion, precut, balloon dilation of intact biliary sphincter, previousPEP) or in patients with known hypersensitivity to NSAIDs.3,7

Decision analyses do not usually take into account ethical aspectsor the adverse effect a strategy can have on other individuals suchas patient family members, doctors, or even the health system it-self. No decision analysis completely characterizes all the economicand social dimensions of a health problem and the consequencesof decisions made in clinical practice may be overlooked.26 In ourstudy, the mortality rate due to PEP for the whole cohort rangedbetween 0.04% and 0.19%. This is consistent with the results ofprevious studies showing a post-ERCP mortality rate rangingfrom 0% to 1.6%.27 Because of the low number of deaths in



the current study, it was not possible to make a reliable estimate ofmortality associated to post-ERCP pancreatitis. However, we rec-ognize that death may be the final result of the broad spectrum of

Gut. 2008;57:16321633.

14. Khoshbaten M, Khorram H, Madad L, et al. Role of diclofenac inreducing post-endoscopic retrograde cholangiopancreatographypancreatitis. J Gastroenterol Hepatol. 2008;23:e11e16.

15. Montano Loza A, Rodriguez Lomeli X, Garcia Correa JE, et al. Effect

Pancreas Volume 00, Number 00, Month 2014 Prevention of PEP: A Cost-effectiveness Analysis10. Mazaki T, Mado K, Masuda H, et al. Prophylactic pancreatic stentplacement and post-ERCP pancreatitis: an updated meta-analysis.J Gastroenterol. 2014;48:343355.

11. Mazaki T, Masuda H, Takayama T. Prophylactic pancreatic stent placementand post-ERCP pancreatitis: a systematic review and meta-analysis.Endoscopy. 2010;42:842853.

12. Choudhary A, Bechtold ML, Arif M, et al. Pancreatic stents forprophylaxis against post-ERCP pancreatitis: a meta-analysis and systematicreview. Gastrointest Endosc. 2011;73:275282.

13. Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trialof rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med.2012;366:14141422.tal volume of ERCP procedures, and comorbidity have been de-scribed as risk factors for post-ERCP mortality.28,29 Therefore,jointly with prophylactic measures, the best approach to avoidPEP and resulting deaths is to establish an appropriate indicationfor ERCP, avoiding diagnostic ERCPs and performing fewer inva-sive diagnostic tests.30

In conclusion, the results of the present decision analysisshow that the pharmacological strategy of rectal NSAID adminis-tration is more cost-effective than plastic pancreatic stent inser-tion, stent plus rectal NSAID administration, or no prophylaxisin preventing PEP. From both the economic and effectivenessperspectives based on published scientific evidence, the strategyof not administering any prophylaxis for PEP should be avoided.

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