Impact of endoscopy-based research on quality of life in healthy volunteers

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1 Online Submissions: doi:1.3748/wjg.v16.i4.467 World J Gstroenterol 21 Jnury 28; 16(4): ISSN (print) 21 Bishideng. All rights reserved. BRIEF ARTICLE Impct of endoscopy-bsed reserch on qulity of life in helthy volunteers Alexnder Link, Gerhrd Treiber, Brigitte Peters, Thoms Wex, Peter Mlfertheiner Alexnder Link, Gerhrd Treiber, Thoms Wex, Peter Mlfertheiner, Deprtment of Gstroenterology, Heptology nd Infectious Diseses, Otto-von-Guericke University, Leipziger St. 44, 3912 Mgdeburg, Germny Alexnder Link, Deprtment of Internl Medicine, Division of Gstroenterology, Bylor Reserch Institute, Bylor University Medicl Center, 35 Gston Ave (H-25) Dlls, TX 75246, United Sttes Gerhrd Treiber, Deprtment of Gstroenterology, Oncology nd Generl Internl Medicine, Zollernlb Clinic, Tuebinger St. 3, Blingen, Germny Brigitte Peters, Institute for Biometry nd Medicl Informtics, Otto-von-Guericke University, Leipziger St. 44, 3912 Mgdeburg, Germny Author contributions: Link A nd Treiber G contributed eqully to this work; Link A, Treiber G, Wex T nd Mlfertheiner P designed the study; Treiber G performed endoscopic exmintions; Link A nd Peters B nlyzed the dt; Link A, Treiber G, Wex T nd Mlfertheiner P wrote the pper. Supported by A Reserch Grnt of Astr-Zenec (Wedel, Germny) Correspondence to: Dr. Peter Mlfertheiner, Professor, Deprtment of Gstroenterology, Heptology nd Infectious Diseses, Otto-von-Guericke University, Leipziger St. 44, 3912 Mgdeburg, Germny. peter. mlfertheiner@med.ovgu.de Telephone: Fx: Received: October 5, 29 Revised: November 13, 29 Accepted: November 2, 29 Published online: Jnury 28, 21 Abstrct AIM: To study the impct of n endoscopy-bsed long-term study on the qulity of life in helthy volunteers (HV). METHODS: Ten HV were included into long-term prospective endoscopy-bsed plcebo-controlled tril with 15 endoscopic exmintions per person in 5 different drug phses. Prticipnts completed short form-36 (SF-36) nd visul nlog scle-bsed questionnires (VAS) for different bdominl symptoms t dys, 7 nd 14 of ech drug phse. Anlyses were performed ccording to short- nd long-term chnges nd compred to the control group. RESULTS: All HV completed the study with durtion of more thn 6 mo. Initil qulity of life score ws comprble to generl popultion. Anlyses of the SF-36 questionnires showed no significnt chnges in physicl, mentl nd totl scores, either in short-term perspective due to different medictions, or to potentilly endoscopic procedure-ssocited long-term cumultive chnges. Anlogous to SF-36, VAS reveled no significnt chnges in totl scores for pthologicl bdominl symptoms nd remined unchnged over the time course nd when compred to the control popultion. CONCLUSION: This study demonstrtes tht qulity of life in HV is not significntly ffected by longterm endoscopy-bsed study with multiple endoscopic procedures. 21 Bishideng. All rights reserved. Key words: Endoscopy reserch; Ethics; Helthy volunteers; Qulity of life Peer reviewers: In C Roberts-Thomson, Professor, Deprtment of Gstroenterology nd Heptology, The Queen Elizbeth Hospitl, 28 Woodville Rod, Woodville South 511, Austrli; Willim Dickey, Professor, Altngelvin Hospitl, Londonderry, BT47 6SB, Northern Irelnd, United Kingdom Link A, Treiber G, Peters B, Wex T, Mlfertheiner P. Impct of endoscopy-bsed reserch on qulity of life in helthy volunteers. World J Gstroenterol 21; 16(4): Avilble from: URL: DOI: INTRODUCTION Endoscopy is the min dignostic tool for exmintion of the upper gstrointestinl trct. The min dvntge 467 Jnury 28, 21 Volume 16 Issue 4

2 of endoscopy in comprison to other non-invsive procedures lies in its bility to obtin tissue biopsies, which permit histologicl evlution of tissues for clinicl s well s bsic reserch [1]. The mjority of endoscopy-bsed phrmcologicl studies re performed in ptients with or without specific disese. Investigtions surrounding this focused ptient popultion yields nswers for only limited number of questions. Studies designed round helthy volunteers (HV) my resolve some of those issues (e.g. by reducing inter-individul differences); lthough t the sme time my open new series of questions. One of the min differences between ptients nd HV is hidden in the dilemm tret the disese in ptients nd do no hrm in HV [2,3]. Hrm cn rise from number of sources such s the study-relted tretment, the endoscopy procedure itself, nd/or other relted discomfort (e.g. multiple blood smples, restriction of dily ctivities). Upper GI-endoscopy is reltively well-ccepted procedure. The mgnitude of discomfort to the exmined person depends upon severl fctors such s previous contct with the exminer, pproprite elucidtion of the procedure, sedtion, investigtor s experience, durtion of exmintion nd the expected benefit from the procedure [4]. Becuse of the potentil therpeutic benefit, it is esier to justify the exmintion of the ptients. Since in most cses, HV cn not expect ny helth-relted dvntges from the procedure, the involvement of HV in endoscopy-bsed reserch is mtter of ethicl concern [5]. Updted recommendtions on ethics in gstrointestinl endoscopy-bsed reserch were discussed nd summrized in the recent Workshop of the Europen Society of Gstrointestinl Endoscopy (ESGE) [6]. The min ethicl considertions were s follows: first, there must be reserch issue tht cn not be dequtely ddressed by the involvement of ptients; nd second, the inherent risk for HV is regrded to be cceptble. However the term cceptble is not well defined nd it is not uncommon tht different scientific nd ethicl committees mke different conclusions concerning endoscopy-bsed studies. Objective methods for ethicl evlution could potentilly be helpful in nrrowing such differences in opinions. Trgeting the qulity of life (QOL) in volunteers could potentilly contribute to objectivity in ethicl questions, however, there re no dt regrding this issue. For this reson we imed to evlute the QOL in HV during endoscopy-bsed reserch. To nswer these questions, we used the previously well-vlidted short-form 36 (SF-36) nd visul nlog scle-bsed questionnires (VAS). In this pilot study, we demonstrte tht n endoscopy-bsed drug tril hs no significnt influence on the QOL in helthy prticipnts even under rigorous conditions nd long-term protocol. MATERIALS AND METHODS Ethicl pprovl nd volunteer recruitment The study design ws pproved by the locl ethics committee of Mgdeburg University Hospitl nd by government uthorities. HV, s defined below, were recruited for the study in ccordnce with the Declrtion of Helsinki principles nd recommendtions of the ESGEworkshop on the ethics of gstrointestinl endoscopybsed reserch [6]. The recruitment of HV ws performed through the distribution of brochures or informtion posters voiding ffilition or dependency of HV to the investigtors. The purpose, risks of the procedure nd the drug-relted side effects were fully explined to prticipnts nd included in the written informed consent (e.g. risk of bleeding due to pltelet inhibitory drugs). HV were informed bout the opportunity to revoke study consent nd cncel prticiption t ny time. At lest 24 h considertion time ws provided to the HV before ll prticipnts provided written informed consent. Due to the extensive study protocol, ll HV were finncilly reimbursed for their time, effort nd contribution to the reserch. Finncil compenstion ws equl in ll HV nd ws modestly clculted bsed on generlly used fctors including compenstion for time (or possible income shortfll due to prticiption in the study), risk, discomfort nd inconvenience. HV Ten HV [8 men nd 2 women, ge 27.8 yers (22-37) nd body mss index 24.7 kg/m 2 ( )] were included in the study bsed on previously described inclusion/ exclusion criteri [7]. Briefly, HV hd no bnormlity t physicl exmintion or during routine lbortory exmintion, no history of relevnt illnesses especilly history of peptic ulcertion, no pregnncy in women nd were negtive for H. pylori infection. Study design The study ws conducted s prospective doubleblind, plcebo-controlled study with cross-over design. The min im of the tril ws to study the influence of severl frequently used drugs on the heling of gstroduodenl lesions (preliminry clinicl results were reported elsewhere) [8]. In ddition, we imed to evlute the impct of the endoscopy-bsed tril on QOL in HV. All volunteers were sked to fill out the questionnires on the dy of ech endoscopy, describing the subjective symptoms nd QOL. Rofecoxib, clopidogrel, prednisolone, esomeprzole or plcebo were given lone nd/or together with cetylslicylic cid (ASA). The endoscopic procedures were performed on dys, 7 nd 14 (Figure 1). The volunteers received one of the test drugs for one week nd the sme drug together with ASA for nother week. Totl durtion of the study ws over 6 mo including 4-wk wshout period between 5 different drug phses. Endoscopy After overnight fsting, the endoscopic exmintion ws performed by n experienced endoscopist (G.T.) using stndrd endoscope (GIF 145, Olympus, Germny). All HV received topicl lidocine 2% for locl nesthesi nd 2 mg of butylscopolminiumbromid intrvenously 468 Jnury 28, 21 Volume 16 Issue 4

3 Dy 7 14 SF-36 VAS questionry blood smple collection endoscopic exmintion VAS questionry blood smple collection endoscopic exmintion SF-36 VAS questionry blood smple collection endoscopic exmintion Figure 1 Flow chrt of the study. The multiple drug study with cross-over design ws divided into 5 phses with test drug lone nd in combintion with low-dose spirin during the second week. On dys, 7 nd 14 of ech study, ten HV were sked to complete the questionnires. Upper GIendoscopy ws performed on the sme dys with 4-wk wsh out period between the different phses. Phses Plcebo Clopidogrel (75 mg/d) Esomeprzole (2 mg/d) Prednisolone (1 mg/d) Rofecoxib (25 mg/d) + spirin (1 mg/d) Wshout period 4 wk (iv) to inhibit gstric nd smll bowel propgtion. Additionlly, midzolm 5 mg ws given iv if requested by the prticipnts. During the procedure, ptients were monitored for hert rte nd oxygen sturtion. After systemtic exmintion of the stomch nd duodenum, multiple biopsies (1 per region, totl of 3 per endoscopy) were tken using stndrd forceps (5 mm mximum open dimeter) from the distl duodenl bulb, ntrum nd corpus. Questionnires: Visul nlog scle nd SF-36 To determine the QOL in HV, we used vlidted Germn version of the SF-36 (short form) questionnire which includes n 8-scle profile: physicl functioning, role physicl, bodily pin, generl helth, vitlity, socil functioning, emotionl role nd mentl helth. These scles further represent two distinct higher-ordered clusters due to physicl nd mentl helth vrince. A lower score in SF-36 indictes greter impirment nd cn rnge from (worst helth) to 1 (best helth). To determine the bdominl symptoms of HV, we used previously vlidted visul nlog scle (VAS) bsed questionnire [9] with the following dimensions of symptoms: bdominl pin, bloting, reflux, nuse, vomiting, dirrhe nd loss of ppetite. The summry symptom score (-7) ws clculted by dding up the vlues of the single scores. A single score vlue from 1-1 ws defined s presence, nd -1 s the bsence of ny symptoms. As shown in Figure 1, VAS questionnires were filled out on dys, 7 nd 14 nd the SF-36 questionnires were filled out before nd fter ech drug phse. The score prmeters of HV were compred to previously evluted control popultion of 28 ptients, who underwent single endoscopic exmintion nd in the bsence of cid suppressive drugs no visible mcroscopic or histologicl bnormlities were found [9]. Sttisticl nlysis All dt were nlyzed using the SPSS 1 (Chicgo, IL, USA) nd Grph Pd Prism 4. (Sn Diego, CA, USA). The differences between the groups were nlyzed ccording to corresponding formul nd rules, using where pproprite pired or unpired t-test nd Friedmn s test (FT) for non-norml distributed dt. For ll comprisons, P-vlue (two-sided) of <.5 ws regrded s significnt. RESULTS Study prticiption All 1 HV completed ll 5 phses of the study with 15 endoscopies per HV. With the exception of 2 individuls who either experienced prolonged bleeding fter biopsies hd been tken or melen (due to the combintion of ASA nd clopidogrel) without development of nemi, there were no further drug- or endoscopy-relted complictions. The VAS nd SF-36 questionnires were completed nd returned in 99.5% nd in 88% of ll cses/time points, respectively. In 91% of endoscopies, HV declined to receive midzolm for sedtion nd received only topicl nesthesi with lidocine 2%. Anlyses of the SF-36 questionnires SF-36 questionnires were nlyzed in regrd to different spects, such s influence of study drugs, different time points, s well s long term chnges in QOL. The physicl, mentl nd totl scores, determined by the short form SF-36 questionnire rnged between 65.6 to 97., 65.3 to 96. nd 75.6 to 97.1, respectively. We found no significnt chnges in physicl, mentl or totl scores either between different medictions or due to prticiption in ech drug phse (dt not shown). Overll chnges in physicl, mentl nd totl scores re shown in Tble 1. For the long-term impct of the intensive endoscopy-bsed tril on the QOL in HV, the SF-36 ssessed dt were compred between bseline (dy during the first phse) nd the lst time point of the lst phse more thn 6 mo lter. Remrkbly, physicl (88.4 ± 6. vs 86.4 ± 6.7), mentl (82.1 ± 8.1 vs 84.6 ± 7.4) nd totl scores (88. ± 5.7 vs 88.6 ± 6.1) showed no significnt chnges over the 6-mo period (Figure 2). 469 Jnury 28, 21 Volume 16 Issue 4

4 Tble 1 Chnges in scores on the SF-36 questionnires in HV ccording to different test drugs before nd fter endoscopic procedures Test drug dy Physicl score P Mentl score P Totl score P Plcebo 88.7 ± ± 4.1 NS 85.7 ± ± 7.8 NS 89.9 ± ± 4.8 NS Esomeprzole 85.7 ± ± 6. NS 83.3 ± ± 6. NS 86.2 ± ± 4.8 NS Clopidogrel 86.6 ± ± 6.7 NS 84. ± ± 8.2 NS 88.1 ± ± 6.3 NS Prednisolone 85.1 ± ± 9.6 NS 81.9 ± ± 6.4 NS 87. ± ± 6.7 NS Rofecoxib 86.2 ± ± 3.1 NS 85. ± ± 4.7 NS 88.3 ± ± 3.1 NS Totl Scores 86.4 ± ± 2. NS 83.5 ± ± 1.2 NS 87.8 ± ± 1.5 NS Test drugs were given for one week lone nd for n dditionl week in combintion with low-dose spirin. Four-week wshout periods were performed between the different drug phses. Results expressed in men ± SD, pired t-test: P >.5 listed s NS. HV: Helthy volunteers. Score Physicl function Role physicl Bodily pin Generl helth Vitlity Single score nlysis reveled tht only generl helth decresed from 84.4 ± 13.1 to 79.4 ± 15.4 (men ± SD; pired t-test P =.23) nd mentl helth incresed from 8. ± 6.8 to 83.2 ± 7.5 (P =.22). Anlyses of physicl symptoms with visul nlog scle (VAS) questionnires Physicl complints were ssessed for different symptoms with VAS nd nlyzed in similr mnner to the SF-36 questionnires. As nticipted, subjective physicl nd emotionl perception even t bseline differed from one person to nother (high inter-individul vribility, dt not shown). Almost 6% of ll complints were due to bdominl pin nd reflux, but these scores showed no significnt chnges when compred with bseline (Figure 3). The rrest complints with < 1% of the mximl score were nuse nd loss of ppetite. To Socil function Role emotionl Mentl helth Before the study After the study Figure 2 Chnges in different multiple dimensions nd physicl, mentl nd totls scores between bseline nd end of study determined by SF-36. During the 6-mo study with cross-over design, 1 HV underwent totl of 15 endoscopic exmintions nd 45 biopsies from the ntrum, corpus nd duodenl bulb. The results re expressed in men ± SD. Dotted line shows the theoreticl mx score from 1. Significnt chnges were observed ( ) for generl (84.4 ± 13.1 vs 79.4 ± 15.4, P =.23 pired t-test) nd mentl helth (8. ± 6.8 vs 83.2 ± 7.5, P =.22 pired t-test). In the remining dimensions, physicl, mentl nd totl scores P >.5. Physicl score Mentl score Totl score Score Vomiting Abdominl pin Reflux Bloting Loss of ppetite Nuse Dirrhe Dy Dy 7 Dy 14 Figure 3 Chnges between different symptoms nd summry scores due to the endoscopy-bsed study determined by visul nlog scle (VAS) bsed questionnires. Upper endoscopies were performed on dys, 7 nd 14 of ech phse. During every mediction phse, HV underwent 3 upper endoscopies with multiple biopsies from the ntrum, corpus nd duodenl bulb. Mximl complint score for ny symptom or summry scores re 1 nd 7, respectively. The results re expressed s men ± SE nd nlyzed using Friedmn's test (P >.5 for physicl, mentl nd totl-scores). evlute the globl chnges we constructed summry score; vlues t bseline (3.2 ± 5.1) were comprble to scores t dy 7 (2.6 ± 3.7) nd dy 14 (3. ± 3.4) nd were less thn 5% of the theoreticl mximl score. Anlyses of the impirment of endoscopic exmintion To nlyze the subjective endoscopy-relted impirment in HV, we used VAS which llows the volunteers to score the procedure-oriented discomfort. In nlogy to physicl complins VAS, we observed high interindividul vribility with the overll rnge vrying from bsence to 8% of mximum possible impirment during the endoscopy. As demonstrted in Figure 4, there ws no significnt difference between self-ssessed scores for complints bout endoscopic procedures (1.4 ± 2., 1.4 ± 1.1 nd 1.35 ± 1.1 for dy, 7 nd 14, RM ANOVA, P >.5). Difference between HV nd controls The VAS-scores from HV were compred with previously 47 Jnury 28, 21 Volume 16 Issue 4

5 Score published VAS-scores from control popultion [9]. The overll men for summry symptom scores of HV nd controls were comprble (HV 2.9 ± 4 nd controls 2.7 ± 4.4, t-test: P >.5) nd ws lower thn 5% of the theoreticlly possible vlue. We found significntly more complints for bdominl pin (.98 ± 1.37 vs.3 ±.8, P =.12) nd vomiting (.22 ±.5 vs.3 ±.2, P =.46) in the HV group (Figure 5), but due to the limited number of HV we could not perform ge djustment for the symptoms. The difference between both scores were below the defined cut-off vlue for the presence or bsence of symptoms nd were significntly lower thn symptomtic popultion s previously published [9]. DISCUSSION Dy Dy 7 Dy 14 Figure 4 Chnges in complince scores due to endoscopic procedures between different time points determined by visul nlog scle (VAS) bsed questionnire. Upper endoscopies were performed on dys, 7 nd 14 of ech phse nd 3 biopsies were tken during ech procedure. Mximl complint score is 1. The results re presented s sctter plots with mens s the lines nd were nlyzed by ANOVA test (P >.5). QOL of HV is one of the mjor ethicl concerns in endoscopy-bsed reserch. Due to the lck of objective dt, the decision to include or not to include HV into clinicl tril is mde rther rbitrrily nd is mostly bsed on the individul judgment of clinicins nd the opinion of expert committees. Therefore, there is strong need for prospective dt tht would help to gin knowledge directly relted to HV. To test if the endoscopy-bsed study impcted the QOL of HV, we prospectively evluted QOL in HV under rigorous conditions. During the study of multiple potentilly GI-hrmful medictions, HV underwent multiple (15) endoscopic exmintions with over 45 biopsies in 5 independent phses. We demonstrted tht by ccurte implementtion of recommendtions nd guidelines, even long-term endoscopy-bsed study hs only little or no impct on the QOL in HV. Severl different methods to mesure QOL, for exmple Sickness Impct Profile, Medicl Outcome Study Short-Form 36 (SF-36), Nottinghm Helth Profile, Qulity of Well Being Scle nd other disesespecific scles hve been previously vlidted [1]. We Symptom score Vomiting Abdominl pin Helthy volunteers Control popultion Reflux Bloting Loss of ppetite Nuse Dirrhe Summry score Figure 5 Different symptoms nd summry scores due to the endoscopybsed study compred in HV nd the control group determined by visul nlog scle (VAS) bsed questionnires. Every HV completed 5 mediction phses with 15 endoscopic exmintions. Control popultion (dt previously published in [9], dopted with permission) underwent only one upper GI endoscopy without endoscopic or histologicl pthology. Mximl complint score for ny symptom or summry scores re 1 nd 7, respectively. The bsolute symptom vlue ws below the cut-off for presence of the symptom. decided to use the SF-36 questionnire for its brevity nd its comprehensiveness. SF-36 is one of the best vlidted nd widely used questionnires both in clinicl prctice nd reserch work in gstroenterology [11]. To increse the relibility of the study, we lso used VAS which ws previously vlidted in dyspeptic ptients by our group [9]. Both questionnires re bsed on self-evlution which minimizes the investigtor-relted impct, nd further contributes to relibility of the outcome results. In this pilot study, we found tht the endoscopy-bsed tril ws not ssocited with significnt chnges in QOL scores. These scores were comprble between different phses nd time points s well s when compred to the generl popultion [12] nd to the control popultion [9]. Bsed on our results nd previous knowledge, severl conclusions cn be mde [6]. First, implementtion of the current guidelines nd recommendtion re relible fundment for the successful reliztion of n endoscopy-bsed study. Second, creful selection of volunteers might be importnt, especilly tking into ccount the motivtion of the HV. Motivtion is - t lest in prt - bsed on n idelistic chrcter, even if finncil compenstion is provided. However, especilly in developing countries, finncil compenstion my become the dominnt stimulus for prticiption which my overcome the study-relted discomfort [5,13]. In our study, inclusion of HV ws bsed on first come, first served principle, however, there is still chnce of creting bis due to personl motivtion, willingness to prticipte in the study or even finncil interest [5,13]. In this regrd it is importnt to mention tht nlogous to other studies, ll the HV were reimbursed for their time, effort nd contribution to the reserch, but finncil compenstion ws modest t best. Since personl motivtion my vry considerbly, testing HV with higher nd lower tolernce Summry symptoms score 471 Jnury 28, 21 Volume 16 Issue 4

6 to endoscopy-bsed studies, especilly in reltion to finncil rewrd, could dd interesting nd vluble informtion nd should be considered in future studies. Besides motivtion, physicin/clinicin nd nursing cre (GCP) lso plys n importnt role in subjective cognition of impired QOL. All endoscopic exmintions were performed by n experienced endoscopy tem which could hve influenced the stisfction, nd thereby tolernce to the procedure [14]. To the best of our knowledge, the only comprble study tht hs ddressed similr issue ws from Adchi et l [15]. This group nlyzed crdic stress in HV without sedtion, nd showed tht endoscopic exmintion of HV without sedtion incresed crdic stress (without ffecting crdic output) by 66% [15]. Although evlution of objective physiologicl prmeters my dd vluble informtion, especilly if correlted to VAS or even SF-36, the correltion to personl impirment is still unknown. The VAS impirment score in our study ws constnt throughout the study, with men impirment of 15% s mximl vlue. Although premediction would improve tolernce to endoscopic procedures, premediction with midzolm ws only used in 9% of procedures. From nother perspective, the socil life of HV my lso hve hd n impct on the decision to use or not use premediction. Necessry dily ctivities like study, work or trnsporttion could be significntly influenced by premediction, especilly becuse the durtion of this study ws 6 mo. Furthermore, it is worth mentioning tht none of the HV interrupted the study, nd ll of them declred tht they would re-prticipte. Some of them did prticipte in lter endoscopy-bsed study with 4 endoscopic procedures within 2 h [7]. It ws not the im of our study to clrify whether endoscopy-bsed reserch is ethicl or not, but primrily to evlute QOL in HV following the implementtion of current recommendtions nd guidelines. Nevertheless, this informtion could indirectly contribute to the ethicl considertions of endoscopy-bsed reserch, if the guidelines nd recommendtions re cceptble. Therefore, sfety stndrds including experienced endoscopists re pre-requisite in such studies. Endoscopy-bsed studies hve some risks for complictions, which in the worse cse cn be lethl, even if volunteers re young nd helthy [16]. However, the risk is negligible if the procedure is crried out with mximum ccurcy nd ccording to the recommendtions for stndrds of sedtion nd monitoring of ptients during GI-endoscopy [3,17,18]. In summry, in this pilot study we show for the first time tht prticiption in long-term endoscopy-bsed trils is not necessrily ssocited with significnt chnges in QOL in HV. Evlution of QOL might be vluble tool regrding ethicl questions in further studies. Lrger studies re wrrnted to confirm the dt nd to further nlyze the interction between QOL nd motivtion of HV. ACKNOWLEDGMENTS The uthors re grteful to Dr. Ajy Goel nd Dr. Klus Moenkemueller for their helpful discussions nd criticl reding of the mnuscript, nd to Mrs. Kthrin Beier, Mrs. Din Worm, Mrs. Mrtin Leucke nd the endoscopy tem for providing excellent cre of the HV. We re lso thnkful to the HV for their commitment to the study. COMMENTS Bckground Involvement of helthy volunteers (HV) is bsolutely essentil in gining vluble knowledge in clinicl nd preclinicl reserch. The involvement of HV (HV) hs long history, but mny unresolved issues of ethicl, methodologicl or even legl concerns in this regrd still remin unnswered. The importnce of this becomes even more pronounced when invsive procedures like GI endoscopy re undertken. Existing ethicl recommendtions nd guidelines on this topic re mostly bsed on the opinion of experts, but mny of these questions hve not been studied in systemtic mnner. Reserch frontiers Multiple studies hve shown tht the motivtion of HV plys key role in recruiting volunteers. Finncil rewrd is one of the crucil motivting fctors in HV. Prticiption in reserch studies might be ssocited with study-relted risks, discomfort nd inconvenience tht might become even more relevnt in endoscopy-bsed studies. Impirment in the qulity of life in HV my ply crucil role in understnding these ethicl concerns, however, so fr no study hs ddressed the impct of endoscopy-bsed reserch on the qulity of life of HV. Innovtions nd brekthroughs In this pilot study the uthors evlute the chnges in qulity of life in HV in long-term endoscopy-bsed drug study. The study ws conducted ccording to existing ethicl recommendtion nd guidelines. Using the well-vlidted SF-36 nd visul nlog scle-bsed questionnires, they show tht endoscopybsed reserch hs no significnt impct on qulity of life in HV even under rigorous conditions. Applictions This study provides vluble nd importnt informtion regrding the qulity of life of HV who prticipte in endoscopy-bsed studies, nd supports the existing recommendtion nd guidelines on this topic in Gstroenterology. Terminology Helthy volunteer: is person who voluntrily prticiptes in reserch study. Volunteer come from volunteering which mens working, prticipting or being involved in something without being motivted by finncil or mteril gin. The historicl intention, such s to promote good, serve society nd improve humn qulity of life show sttic movement in pid volunteerism. Endoscopy-bsed reserch: re studies or trils performed on individuls which involve endoscopic techniques. Short Form 36: is well-vlidted nd widely used short survey which includes 36 specific questions on helth-relted qulity of life. Peer review This study exmines the impct of demnding endoscopy protocol on gstrointestinl symptoms nd qulity of life in 1 humn volunteers. The study involved 15 endoscopic procedures over period of 6 mo. REFERENCES 1 Swin CP. New Thechnology in dignostic nd therpeutic endoscopy. In: Clssen M, Tytgt GNJ, Lightdle CJ, editors. Gstroenterologicl endoscopy. Stuttgrt: George Thieme Verlg, 22: Hope T, McMilln J. Chllenge studies of humn volunteers: ethicl issues. J Med Ethics 24; 3: Treiber G, Mlfertheiner P. Endoscopy-bsed reserch in helthy volunteers. Dig Dis 22; 2: Ko HH, Zhng H, Telford JJ, Enns R. Fctors influencing ptient stisfction when undergoing endoscopic procedures. Gstrointest Endosc 29; 69: , quiz 891.e1 5 vn Gelderen CE, Svelkoul TJ, vn Dokkum W, Meulenbelt J. Motives nd perception of helthy volunteers who prticipte 472 Jnury 28, 21 Volume 16 Issue 4

7 in experiments. Eur J Clin Phrmcol 1993; 45: Mlfertheiner P, Mntzris GJ, Frhing M, Niv Y, Escourrou J, Treiber G, Di Mrio F, Reymond MA. Recommendtions of the ESGE workshop on Ethics in Gstrointestinl Endoscopy-Bsed Reserch. First Europen Symposium on Ethics in Gstroenterology nd Digestive Endoscopy, Kos, Greece, June 23. Endoscopy 23; 35: Treiber G, Wex T, Link A, Vieth M, Lufer S, Mlfertheiner P. The effect of single-dose nproxen on eicosnoid formtion in humn gstroduodenl mucos. Aliment Phrmcol Ther 26; 23: Treiber G, Vieth M, Wex T, Mlfertheiner P. Impct of Aspirin nd Comedictions On Heling of Biopsy-Induced Gstroduodenl Erosions. Digestive Disese Week 26. Los Angeles, CA, USA. Gstroenterology 26; 13 (4 Suppl 2): Treiber G, Schwbe M, Ammon S, Wlker S, Klotz U, Mlfertheiner P. Dyspeptic symptoms ssocited with Helicobcter pylori infection re influenced by strin nd host specific fctors. Aliment Phrmcol Ther 24; 19: Ycvone RF, Locke GR 3rd, Provenzle DT, Eisen GM. Qulity of life mesurement in gstroenterology: wht is vilble? Am J Gstroenterol 21; 96: Wre JE Jr, Sherbourne CD. The MOS 36-item short-form helth survey (SF-36). I. Conceptul frmework nd item selection. Med Cre 1992; 3: Brzier JE, Hrper R, Jones NM, O Cthin A, Thoms KJ, Usherwood T, Westlke L. Vlidting the SF-36 helth survey questionnire: new outcome mesure for primry cre. BMJ 1992; 35: Tishler CL, Brtholome S. The recruitment of norml helthy volunteers: review of the literture on the use of finncil incentives. J Clin Phrmcol 22; 42: Ycvone RF, Locke GR 3rd, Gostout CJ, Rockwood TH, Thieling S, Zinsmeister AR. Fctors influencing ptient stisfction with GI endoscopy. Gstrointest Endosc 21; 53: Adchi W, Yzw K, Ow M, Koide N, Hnzki K, Kjikw S, Kobyshi S, Amno J. Quntifiction of crdic stress during EGD without sedtion. Gstrointest Endosc 22; 55: Pentz RD. Spreding it round: money for resercher nd reserch prticipnts. Mt Sini J Med 24; 71: Aisenberg J, Cohen LB. Sedtion in endoscopic prctice. Gstrointest Endosc Clin N Am 26; 16: Orme M, Hrry J, Routledge P, Hobson S. Helthy volunteer studies in Gret Britin: the results of survey into 12 months ctivity in this field. Br J Clin Phrmcol 1989; 27: S- Editor Tin L L- Editor Webster JR E- Editor M WH 473 Jnury 28, 21 Volume 16 Issue 4