Contemporary Clinical Trials

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1 Contemporry Clinicl Trils 33 (2012) Contents lists vilble t SciVerse ScienceDirect Contemporry Clinicl Trils journl homepge: A Mediterrnen dietry intervention in persons t high risk of colon cncer: Recruitment nd retention to n intensive study requiring biopsies Zor Djuric,b,, Mck T. Ruffin IV, Mry E. Rpi, Mri L. Cornellier, Jinwei Ren, Thoms G. Ferreri, Leh M. Askew, Annd Sen,c, Den E. Brenner d,e, D. Kim Turgeon d Deprtment of Fmily Medicine, University of Michign, Ann Arbor, MI 48109, United Sttes b Deprtment of Environmentl Helth Sciences, University of Michign, Ann Arbor, MI 48109, United Sttes c Deprtment of Biosttistics, University of Michign, Ann Arbor, MI 48109, United Sttes d Deprtment of Internl Medicine, University of Michign, Ann Arbor, MI 48109, United Sttes e Deprtment of Phrmcology, University of Michign, Ann Arbor, MI 48109, United Sttes rticle info bstrct Article history: Received 24 October 2011 Received in revised form 13 My 2012 Accepted 19 My 2012 Avilble online 26 My 2012 Keywords: Colon biopsy Recruitment Dietry intervention Cncer prevention This study recruited persons t incresed risk of colon cncer to n intensive dietry intervention study tht required biopsies of the colon by flexible sigmoidoscopy t bseline nd fter six months of intervention. A totl of 1314 individuls contcted the study, nd only 16 individuls indicted tht the sigmoidoscopy procedure ws n obstcle to study prticiption. A totl of 270 individuls completed screening visit nd signed screening consent form. Inquiries bout the study tended to be fewer in the winter nd lte summer. Filure to return food records ws the most common reson for exclusion. Dietry recll t enrollment indicted tht subjects were consuming significntly more vegetbles, lower sodium nd lower glycemic lod on the dy before strting the study vs. during the eligibility phse which might hve n impct on biomrker mesures. This mkes it importnt to cpture dietry chnges in the period between determintion of eligibility nd enrollment. Subjects (n=120) were rndomized to follow Helthy Eting or Mediterrnen Diet, ech of which required substntil dietry record-keeping. The study completion rte ws 78%, nd subjects reported high stisfction with study prticiption. Of the 93 individuls who completed the study, only one refused the flexible sigmoidoscopy t the finl visit. These findings suggest tht flexible sigmoidoscopy does not pper to be brrier for recruitment of high-risk individuls to n intensive dietry intervention tril, but tht completing food records cn be Elsevier Inc. Open ccess under CC BY-NC-ND license. 1. Introduction Everypersonintheindustrilized world hs on verge one in twenty chnce of developing colorectl cncer in their lifetime, nd the incidence in the U.S. is mong the highest in the world [1 3]. Mny epidemiologicl studies hve investigted the role Abbrevitions: BMI, body mss index;mufa, monounsturted ft;pufa, polyunsturted ft;pge2, prostglndin E2;SFA, sturted ft Corresponding uthor t: 1500 E. Medicl Center Drive, Room 2150 Cncer Center, University of Michign, Ann Arbor, MI , United Sttes. Tel.: E-mil ddress: zorlong@umich.edu (Z. Djuric). tht diet my ply in the incresed rtes observed in Western countries, nd the vilble evidence points to protective effect of Mediterrnen diets [4 7]. A Mediterrnen diet encompsses low omeg-6 ft intke nd higher omeg-3 ft intke, higher monounsturted ft (MUFA) intke from olive oil, lower red met, less refined crbohydrtes nd incresed vriety nd quntity of fruits nd vegetbles [4]. Despite the promising cncer-preventive properties of Mediterrnen diets, there hve been few intervention studies reported using this type of diet in Americn popultions. This study recruited subjects t incresed colon cncer risk since this would be likely trget popultion for prevention [8]. Recruitment to prevention trils is, however, Elsevier Inc. Open ccess under CC BY-NC-ND license. doi: /j.cct

2 882 Z. Djuric et l. / Contemporry Clinicl Trils 33 (2012) difficult even though one would expect good interest from high risk popultion. Typiclly lrge numbers of individuls need to be contcted, nd often recruitment requires more time thn envisioned [9,10]. This is especilly true when invsive procedures re required since the optiml biomrkers for enhncing our knowledge of the links between diet nd cncer re generlly tissue-bsed [11,12]. Flexible sigmoidoscopy is well-ccepted procedure for colon cncer screening, nd it cn be used to obtin colon biopsies tht re vluble for biomrker reserch [13].The present study required two flexible sigmoidoscopies of the colon, substntil mount of dietry counseling nd regulr dietry record-keeping. The study used screening consent to llow cpture of informtion bout the individuls who were nd were not enrolled. This cn help cpture possible bis in study enrollment, which is importnt since it cn ffect the pplicbility nd interprettion of the results [14]. Here we describe recruitment nd retention strtegies, chnges in diet before the flexible sigmoidoscopy procedure, nd stisfction with study prticiption. This provides guidnce for future studies involving intensive dietry intervention nd invsive procedures. 2. Methods 2.1. Eligibility The Helthy Eting for Colon Cncer Prevention Study ws pproved by the University of Michign Institutionl Review Bord (HUM ). The study ws listed on the clinicl trils website mintined by the Ntionl Institutes of Helth (registrtion number NCT ). The study enrolled persons t incresed risk for colon cncer in n effort to mximize the evlution of the intervention effects on biomrkers of colon cncer risk. The inclusion criteri for the study required n incresed risk for colon cncer s defined by hving either strong fmily history of colon cncer or prior denomtous polyp or resected erly (Dukes A, B or C) colon cncer. Individuls with previous colon cncer were t lest two yers post tretment for cncer, with the exception of curtive surgery for smll lesions, such s endoscopiclly removed cncers. For other cncers, the eligibility criterion ws to be t lest five yers post ny type of cncer tretment. A strong fmily history ws defined s hving one first degree reltive or two second degree reltives with colon cncer. Eligible subjects were in good generl helth nd not expecting mjor lifestyle chnges in the next 6 months. Dietry eligibility criteri included t lest 23% of clories from ft with no more thn 48% of fts s MUFA nd no more thn 5.5 servings/dy of fruits nd vegetbles. This ws determined from the verge of two dys of food records nd one un-nnounced 24-hour recll. Subjects lso hd to hve telephone nd spek English since the counseling ws done lrgely by phone. Exclusion criteri included being on mediclly prescribed diet, tking dietry supplements or medictions tht would interfere with the dietry chnges, being pregnnt or lctting, ge less thn 25 since the recommended dietry llownces differ for young persons, nd conditions tht would interfere with biomrker mesures in the colon such s colitis nd hereditry polyposis. Persons with BMIb18.5 or >35 kg/m 2 were excluded since low BMI could indicte eting disorders nd high BMI vlues, bove the midpoint of the obesity rnge, could indicte more prevlent helth problems nd these persons cn be more difficult to counsel. Mximum llowed spirin use ws either 81 mg/dy or 325 mg spirin every other dy for prevention of crdiovsculr disese. Subjects were sked to tke cetminophen for occsionl pin Recruitment strtegies The recruitment pln included mny different chnnels. A study flyer nd brochure were creted tht included informtion on bsic eligibility criteri nd bsic informtion on study design: there were two diets, study procedures could tke up to 3 h nd pyment for completing 6 months of study dded up to $300. Informtion on flexible sigmoidoscopies ws given when subjects contcted the study since this would be too complex to explin on flyer. The study flyer ws posted in the hospitl nd reserch complex common res, nd in multiple community loctions: physicins' offices, community bulletin bords, churches, exercise fcilities, nd librries. An institutionl website contining informtion on ll studies t the University of Michign lso listed the study. Other non-specific recruitment strtegies included press relese which resulted in newspper stories bout the study, brochure distribution t helth firs, nd pid dvertisements in locl newsppers. Specific strtegies trgeted t high risk individuls included nnouncements bout the study during events for colon cncer wreness month ech yer, recommendtions to ptients mde by gstroenterologist, flyer posting in the medicl gstroenterology suite, study newsletter sking current study prticipnts to refer nyone they my know nd trgeted milings. The trgeted milings were done using electronic helth records of five lrge locl primry cre physicin's offices to identify ptients t incresed risk for colorectl cncer. Letters from the ptient's primry physicins were then miled by the study stff informing the ptient bout the study. Finlly, the cll center for the University of Michign Comprehensive Cncer Center referred ptients who expressed n interest bout studies on colon cncer. All promotion of the study provided telephone, nd emil contct informtion for the study tem Screening of interested prticipnts The study coordintor clled ll interested persons to confirm the study requirements nd review the eligibility requirements. Subjects were told bout the flexible sigmoidoscopy on the phone nd were told tht this procedure required less thn 10 min nd did not require colonic preprtion, sedtion, or pin medictions. Persons still interested nd eligible for the study then scheduled n in-person ppointment to be further screened for eligibility. This ppointment required bout 30 min nd ws conducted in n outptient clinicl reserch fcility either within thehospitlortnoffsitemediclofficebuilding.duringthe screening visits, interested persons were sked to sign written informed consent to be screened for the study. This consent llowed for the cpture of informtion bout the individuls who were nd were not enrolled. This method llows for cpturing potentil bis in the study enrollment process. Subjects were sked to complete food records on Sundy nd Mondy nd to return those in postge pid envelope by mil. After the food record ws returned to the reserch

3 Z. Djuric et l. / Contemporry Clinicl Trils 33 (2012) tem, the subject ws clled for n unnnounced 24-hour recll. Subjects were enrolled in the study on verge 50 dys fter completing the 24-hour recll, minly due to scheduling issues. The dietry eligibility requirements were confirmed using n verge of those three dys Study design The recruitment gol for the study ws 120 high-risk subjects, nd this ws bsed on considertions of the chnges tht might be expected in biomrker endpoints in the colon. Prticipnts were rndomized within four strt: body mss index (BMI, norml weight or overweight/obese s defined by BMI 25 kg/m 2 ), regulr spirin use (Yes/No), gender (mle/ femle), nd risk sttus (personl history of cncer or not). These eligibility criteri were importnt since they could ffect the colonic biomrkers of dietry complince nd of prostglndin (PG) E2 formtion. Higher BMI hs been ssocited with higher n 6 nd lower n 9 nd n 3 ftty cids in dipose tissue, which re mrkers of dietry complince, nd BMI lso cn ffect PGE2 levels, which is biomrker of colon cncer risk [15,16]. Incresed BMI is ssocited with incresed oxidtive stress nd inflmmtion, which induces PGE2 formtion [17]. Low dose spirin use would still llow for detection of further decreses in PGE2 levels in the colon with diet [18]. The ctegoriztion of subjects by gender nd whether or not they hd colon cncer in the pst ws used to ensure equl representtion in the two study rms. It is possible tht plsm ftty cids nd crotenoids cn vry by these fctors, mking equl representtion of subjects in these ctegories between the two study rms potentilly importnt [19,20]. The two diets in the study were Helthy Eting diet tht ws bsed on Helthy People 2010 recommendtions nd modified Mediterrnen diet. Both study rms required weekly telephone counseling for one month, biweekly counseling for the next two months nd monthly counseling for the finl three months. All subjects received rm-specific bimonthly newsletters contining notes on study recruitment progress, sesonl cooking hints, recipe nd prticipnts re sying column to rely helpful discoveries or comments mde by current study prticipnts. In the Helthy Eting rm, gols included consumption of 2 servings/dy of fruit, 3 servings/dy of vegetbles with t lest one of those servings being drk green or ornge, 3 servings/ dy from whole grins, less thn 10% of clories from sturted ft nd less thn 30% of clories from totl ft. Subjects were sked to complete self-monitoring booklets to enumerte dily servings of fruits, vegetbles, nd whole grins nd grms of sturted ft. In the Mediterrnen rm, dietry gols were bsed on n exchnge list tht clssified foods into ctegories. There were dily gols from ech ctegory, giving individuls flexibility in food choices for meeting the study gols. This type of pproch would be expected to mximize the long-term complince tht is required for reduction of cncer risk. The ft gol ws to chieve PUFA:SFA:MUFA rtio of 1:2:5. Consumption of foods high in omeg 3 ftty cids ws requested t lest twice week, nd the whole grin gol ws t lest three servings/dy. To ensure intke of fruit nd vegetbles ner Cretn levels, the gol ws for consuming 7 9 FDA servings per dy, depending on totl cloric intke (7/dy for b1700 kcl/dy, 8/dy for kcl/d nd 9/dy for >2000 kcl/d; 7 servings cn weigh bout 600 g). The fruit nd vegetble exchnge lists encourged vriety of intke with dily intke gols for specific types of vegetbles (including t lest one drk green vegetble or herb) nd fruits, similr to wht we used previously [21]. This published exchnge list ws modified to include ctegories for high omeg 3 foods nd whole grins Study procedures Subjects were sked to rrive t the bseline nd 6-month study visits in the fsting stte. The study visits consisted of providing blood smple, eight colon biopsies obtined by flexible sigmoidoscopy, questionnires, 24-hour dietry recll, nd mesures of height, weight, wist nd hip circumference, nd blood pressure. Study prticipnts were provided with brekfst nd prking voucher. There ws lso 3-month visit for checking body weight, filling out brief questionnires nd meeting with the study dietitin. Prticipnts were pid $130 t 0 nd 6 months nd $40 t 3 months for their time nd inconvenience in coming to the clinic, nd for ny incresed food costs. Biopsies of the colon were obtined by flexible sigmoidoscopy without ny prior preprtion to empty the intestinl trct. The preprtion procedure for colonoscopy cn be detriment to ccrul nd my lter eicosnoid concentrtions in the mucos. Eight un-prepped biopsy smples of norml mucos (bout 5 mg ech) were obtined so tht enough tissue would be vilble for ftty cid nlysis (1 biopsy), n eicosnoid profile (2 biopsies), crotenoid nlysis (1 biopsy), prolifertion/nucler morphology (2 fixed biopsies) nd two frozen biopsies for future use. The biopsies were obtined circumferentilly 15 cm bove the nus using biopsy forceps Sttisticl nlyses Descriptive summry mesures were obtined for the study prticipnts. Chrcteristics of the screened subjects were compred between the study prticipnts nd the ones who did not go on the study by mens of two-smple t-test for men comprison nd chi-squre test of compring proportions s pproprite. After rndomiztion of the study prticipnts, the two rms were gin compred in similr mnner to investigte ny imblnce cross them. A similr comprison ws crried out between the group of study completers (93 subjects) nd the non-completers (27 subjects). Dietry intke ws ssessed for eligibility pproximtely one month before study enrollment nd by 24-hour recll t the bseline visit. This ws done to obtin dt on recent diet since this might ffect the serum nd colon biomrker mesures. The two mesures of dietry intke were compred for ny differences by mens of pired t-test. All study completers lso completed questionnire regrding study stisfction tht sked vrious questions regrding the study on 5-point scle with 5 being very much so nd 1 being not t ll. The item responses were fctor nlyzed using the principl component extrction methods with vrimx rottion. The fctor scores were subsequently nlyzed in liner regression frmework with the scores s (continuous) outcomes, nd the study rm indictor s the primry fctor. The models were controlled for ge s

4 884 Z. Djuric et l. / Contemporry Clinicl Trils 33 (2012) covrite. The regression models were further run using weighted lest squres pproch, with weights clculted vi the response propensity method. Specificlly, the weights for the prticipnts were clculted s the reciprocl of the probbility of completing the study, with the probbilities being estimted from logistic regression with completion or non-completion s outcome, ge, bseline vegetble consumption, mritl nd smoking sttus being independent vribles. 3. Results During the enrollment period from to July 1, 2007 to October 15, 2010, there were 1314 inquiries received bout study prticiption (Tble 1, Fig. 1). Inquiries bout the study, nd screening visits, were most plentiful in the summer nd fll, with lower numbers of inquiries in the winter nd August (Fig. 2). Most of the inquiries cme from femles, perhps becuse women trditionlly re more involved in mking fmily mels. Telephone ws the most often used method of contct, but substntil number of inquiries were by emil. Emil ws useful method of contct s it Tble 1 Study recruitment to the Helthy Eting Study from July 1, 2007 through October 15, Inquiries Number Totl 1314 Gender Mle 372 Femle 890 Unknown 52 Type of inquiry Emil 488 Phone 826 Source of inquiries Posted flyer 277 Clinicl trils website 257 Newspper rticles bout study 70 Word of mouth 58 Physicin referrl b 32 Other c 85 Resons for lck of follow-up Ineligible d 625 No response e 347 Live too fr wy 17 Did not wnt flexible sigmoidoscopy 16 Wnt to lose weight 9 Tking high dose NSAIDs or supplements 8 Other resons 22 Completed study screening visit 270 The University of Michign supported clinicl trils website for the community clled Engge tht listed the study nd the bsic eligibility requirements. b Physicin referrl ws obtined through physicins in the Deprtment of Fmily Medicine. Providers identified potentilly eligible ptients, nd the study then sent letter nd study brochure to 280 subjects, 32 of whom responded by contcting the study. c Other sources of recruitment were listing of the study in University of Michign lumni electronic newsletter, the hospitl website, nd referrl from the cll center. d Ineligible individuls lcked colon cncer risk fctors (n=282) or were ineligible for other resons such s medicl conditions or being bove the upper BMI limit. e Emil inquiries ccounted for 307 of the no response ctegory, with the remining 40 resulting from not being ble to return cll from either cll center messge or nswering mchine. Anlysis Follow-Up Alloction Enrollment Screening Mediterrnen Diet (n = 59) Withdrwls (n = 12) No contct (n = 6) Too busy (n = 6) Inquiries (n = 1314) Assessed for eligibility (n = 270 ) Rndomized (n = 120) Excluded (n = 924) Excluded (n = 150) Helthy Eting Diet (n = 61) Withdrwls (n = 12) No contct (n = 7) Too busy (n = 3) Illness in fmily (n = 2) Removed (n = 3) Finished Study (n = 47) Finished Study (n = 46) Fig. 1. Recruitment nd retention in the Helthy Eting Study. Three individuls were removed from study either due to initition of supplement use (fish oils, high level thimine) or diet chnge (incresed sodium intke recommended by physicin). required miniml stff time, but of the 488 individuls who responded vi emil, 307 did not reply fter more informtion bout the study ws sent to them. Interestingly trgeted recruitment methods such s physicin referrl or personl referrl to individuls who might be eligible yielded only minority of the inquiries (Tble 1). Flyers nd posting on the university's clinicl tril website were the methods tht yielded the lrgest number of inquiries. Of the 1314 persons who inquired bout the study, bout hlf were not eligible (625) nd only 16 indicted tht they were not interested becuse of the flexible sigmoidoscopy procedure. A totl of 270 subjects completed study screening visit. The screening visit served to verify eligibility fctors in person nd to provide instructions for completing food records so tht dietry eligibility could be verified. Of the 245 individuls who were sked to keep food records, 69 did not return food record. Keeping food records cn be tedious, but hving the bility to complete food records ws n importnt spect of eligibility since complying with the dietry gols of the study required substntil mounts of dietry recordkeeping. Only 35 (20%) of the returned food records indicted diet tht ws not eligible, nd the most common reson ws n intke of fruits nd vegetbles tht ws too high. The demogrphic chrcteristics of subjects who were or were not enrolled did not differ significntly, nd bout 8% hd both previous denom nd strong fmily history of colon cncer (Tble 2). Subjects enrolled in the study were strtified by four fctors tht could ffect the outcome mesures: gender, BMI, spirin

5 Z. Djuric et l. / Contemporry Clinicl Trils 33 (2012) inquired screened Number of Persons Month Fig. 2. Number of persons who inquired bout the study or were screened, shown by clendr month from 2007 to use nd whether or not they hd colon cncer in the pst. This resulted in 61 subjects being rndomized to the Helthy rm nd 59 to the Mediterrnen rm. Only one subject hd colon cncer in the pst. Tble 3 shows tht the rndomiztion ws effective for equlizing demogrphic chrcteristics of the subjects on ech rm. The subjects tended to be Cucsin nd well educted. The lrgest group of subjects were from Ann Arbor, MI (n=44) but most of the subjects were from nerby communities including Detroit suburbs (n=29), Ypsilnti (n=16), Grnd Rpids nd Lnsing re (n=7), nd severl smll communities within 30 mile rdius of Ann Arbor Tble 2 Chrcteristics of screened subjects given s men nd SD, or number nd percent. Chrcteristic On study, n=120 Not on study, n=150 Age, yers 52, 12 (rnge 22 82) 51, 12 (rnge 21 85) Femle 86, 72% 97, 65% Body mss index, kg/m 2 27, 4 (rnge 19 35) 28, 4 (rnge19 41) Regulr spirin user b 24, 20% 28, 19% Previous denom 33, 28% 29, 19% Fmily history of 87, 76% 97, 65% colon cncer c Both risk fctors d 10, 8% 12, 8% Resons subjects did not go on study were: did not meet eligibility criteri (n=25), did not return food records (n=69 of 245 potentilly eligible persons), dietry intke not eligible (n=35), dietry issues tht would interfere with counseling (such s ets out too much or food record indequte, n=15), nd not interested (n=6). b Regulr spirin users were individuls tking low dose spirin (typiclly either 81 mg/dy or 325 mg every other dy) for prevention of crdiovsculr disese. c One person who enrolled in the study with fmily history of cncer lso hd personl history of colon cncer. Three people who did not enroll hd personl history of colon cncer but no fmily history or previous denoms. At the screening visit, it ws determined tht n dditionl nine people who were not enrolled did not fulfill the fmily history or prior denom requirement. d Persons who were not sure if their colon polyps were denoms were not included s hving denoms. This ws true for six persons who enrolled in the study nd nine persons who did not enroll. All of these individuls fulfilled the fmily history requirement of one primry reltive or two secondry reltives with colon cncer. (n=24). About 20% were regulr spirin users nd 15% were smokers. Dietry intke ws ssessed for eligibility pproximtely one month before study enrollment nd by 24-hour recll t the bseline visit. This ws done to obtin dt on recent diet since this might ffect the serum nd colon biomrker mesures more thn intke t eligibility determintion. The nlysis of dietry intke indicted better qulity diets, on verge, for the recll done t study enrollment. This ws sttisticlly significnt for sodium, glycemic lod nd vegetble intke, but differences were not lrge (Tble 4). On verge, totl ft intke in this study popultion ws bout 31% of clories, which is just below the verge intke in the United Sttes from the Ntionl Helth nd Nutrition Exmintion Survey (NHANES) of bout 36% of clories from ft for Cucsin dults [22]. Other spects of study subjects' diets were lso closer to recommendtion vs. usul Americn intkes including higher fruit, vegetble nd fiber intkes [22]. The percentge of subjects remining on study fter 6 months ws 78%, which is consistent with tht observed in Tble 3 Chrcteristics of study subjects in ech study rm given s men nd SD or number nd percent. Chrcteristic Helthy Eting diet Mediterrnen diet n=61 n=59 Age, yers 50, 14 (rnge 22 72) 55, 10 (30 82) Femle gender 43, 70% 43, 73% BMI, kg/m 2 27, 4 (rnge 19 34) 28, 4 (rnge 20 35) Regulr spirin user 11, 18% 13, 22% Cucsin rce 55, 90% 50, 85% Mrried/committed 41, 67% 35, 59% College grdute 47, 77% 45, 76% Tobcco user b 7, 11% 10, 17% History of denoms 16, 26% 17, 28% Fmily history of 41, 67% 36, 61% colon cncer Both risk fctors 4, 7% 6, 10% Persons of other rcil ctegories enrolled in the study were 9 Africn Americns, 1 mixed, 3 Asin nd 1 Ntive Americn. b There were five smokers nd two smokeless tobcco users in the Helthy Eting rm nd ten smokers in the Mediterrnen rm.

6 886 Z. Djuric et l. / Contemporry Clinicl Trils 33 (2012) Tble 4 Dietry Intke during eligibility determintion nd on the dy before study enrollment given s men nd SD for ll 120 enrolled subjects. Nutrient or food group Eligibility At study enrollment Energy, kcl/dy 2123, , 185 Sturted ft, % of energy 11.8, , 0.4 Monounsturted ft, % of energy 12.7, , 0.4 Polyunsturted ft, % of energy 7.1, , 0.3 Sodium, g/dy 3368, , 140 b Clcium, mg/dy 871, , 81 Fiber, g/dy 22, 1 24, 2 Glycemic lod, vs. bred 200, 7 183, 8 b Fruit, servings/dy 1.7, , 0.2 Vegetbles, servings/dy 2.8, , 0.2 b Whole grins, servings/dy 1.9, , 0.2 b A flexible sigmoidoscopy ws performed t the study enrollment visit. Significntly different thn intke t eligibility by the pired t-test. other intensive dietry studies [23,24]. The demogrphic chrcteristics of subjects who did or did not complete the study were similr with the following exceptions. Subjects who completed the study hd higher bseline vegetble intkes nd higher ge t bseline. Non-completers were somewht more likely to be smokers (p=0.06) nd un-mrried (p=0.07). Most of the drop-outs occurred before the 3-month visit; only two subjects left the study fter the 3-month time point. Despite the fct tht this ws n intensive dietry intervention study, with totl of 12 plnned contcts over 6 months, stisfction with study prticiption ws high (Tble 6). Most subjects thought they were ble to follow the diet to which they were rndomized, it ws not too burdensome to be in the study, would recommend the diet nd wnted to keep following the diet. An verge nswer of 4.5 would indicte nswers of very much so or somewht on 5-point scle. The verge nswer ws neutrl when sked whether or not the diet tkes more time thn their usul diet. The similrity in responses between subjects rndomized to the two diets ws surprising since the Mediterrnen group hd much lrger number of dietry gols. When sked the question wht ws the hrdest prt of being in the study, responses in the two study rms were gin similr with the following ctegories of nswers (some subjects gve more thn one nswer, 5 subjects gve no nswer): spects of buying food/eting/cooking n=48, recordkeeping n=21, nothing n=17, flexible sigmoidoscopy n=5 nd other n=5. When sked wht ws the esiest prt of being in the study, the ctegories of nswers were: spects of helthy eting n=57, intercting with the dietitin n=10, recordkeeping n=7, lerning n=3 nd other n=6. A fctor nlysis of the ten stisfction survey item responses reveled existence of three fctors. All fctors hd ssocited eigenvlues lrger thn 1 nd collectively the fctors ccounted for more thn 50% vribility. The first fctor (Fctor 1) hd four items loded highly on it with loding coefficients lrger thn 0.48 in mgnitude. The items were feel good bout being the study, diet ws esy to follow, hve time to follow diet, recommend diet to fmily nd friends. This fctor clerly represented group of subjects tht were stisfied with the most spects of the study. By contrst, Fctor 2 hd three items loded highly ll of which cn be ssocited with stress nd difficulty experienced by the subjects on the study. These three items were diettkesmoretimethnusuldiet, being in the study ws stressful, nd finishing is like weight being lifted. The third fctor (Fctor 3) lso comprised of subjects with positive impression who would recommend diet to fmily nd friends, wnt to keep following the diet, nd would like phone clls to minimize ppointments. One item, nmely others t home mke it difficult to follow diet did not lod sufficiently highly on ny of the fctors. Bsed on the liner regression nlysis, however, none of these fctors were significntly different cross the two diet rms, indicting tht the stisfction (or lck of it) ws not prticulrly function of the specific diet regime, nd ws probbly more reflection of the generl ttitude. It is interesting to note tht ge exhibited significntly positive ssocition (pb.001) with Fctor 1 indicting tht older subjects hd higher overll stisfction level. The weighted nlysis did not revel nything different. 4. Discussion This study recruited individuls t incresed risk of colon cncer to n intensive dietry intervention study. In order to recruit individuls with either prior denomtous polyp or strong fmily history of colon cncer, generlized recruitment with flyers nd website listing proved to yield the highest number of inquiries bout the study (Tble 1). Interestingly dvertisements in locl newsppers, which likely rech lrge number of individuls, were not s successful. We do not hve dt on which flyer posting loction yield the most inquiries, but flyers t the medicl center nd the clinicl trils website re likely viewed by individuls who re fmilir with the medicl center. It might be the cse tht individuls fmilir with the medicl center might be more inclined to volunteer for study being conducted there. It ws, however, surprising tht letters miled to ptients of physicins ffilited with the medicl center only yielded n 11% response rte. The flyers for the study mentioned tht study procedures cn tke some time but the flyers did not indicte tht flexible sigmoidoscopy ws required. It ws felt tht explining this procedure would be complicted nd tht individuls might confuse it with colonoscopy, which is much more involved nd requires preprtion of the bowels. When individuls clled or emiled to inquire bout the study, they were then told bout the procedure, wht it entils nd how long it tkes. After being told bout flexible sigmoidoscopy, very few individuls indicted tht they would not prticipte becuse of this, lthough we cnnot exclude tht this might hve been reson for t lest some of the individuls who did not reply or further pursue prticiption (Tble 1). Individuls t incresed risk for colon cncer likely hve hd t lest one colonoscopy, with the exception of very young individuls, nd in comprison unprepped flexible sigmoidoscopy is much esier to tolerte thn full colonoscopy with preprtion. After six months of study prticiption, one subject did refuse the flexible sigmoidoscopy, however, nd five of 93 subjects who completed the study indicted tht this ws the hrdest prt of the study. The study screening procedure included fce-to-fce visit, nd screening consent form ws required. This screening consentprovedtobevlublesinceitllowedforcptureof informtion bout screened subjects. A recent review of the literture on bis rising from recruitment nd retention issues hs indicted tht very few studies described the screened popultion nd reported drop-out rtes [14].Here we were ble to show tht the demogrphic chrcteristics of screened nd

7 Z. Djuric et l. / Contemporry Clinicl Trils 33 (2012) enrolled subjects were not significntly different (Tble 2). Rndomiztion entiled 16 strt, nd this ws effective for equlizing the demogrphic chrcteristics cross the two study rms, but it did result in slightly uneven number of subjects in the two rms (59 vs. 61). Subjects in the Mediterrnen rm were, on verge, slightly older thn in the Helthy Eting rm, but this ws not significnt (Tble 3). Subjects who did or did not complete the study lso hd similr demogrphic chrcteristics, nd this should minimize bis in the interprettion of the results (Tble 5). One importnt considertion for this study ws whether or not recent diet would ffect the biomrkers being mesured, especilly in the colon. In ddition, dietry nlyses for determining study eligibility were typiclly completed 6 weeks prior to strting on study. The comprison of dietry intkes used for eligibility determintion nd the 24-hour recll tken t the bseline visit indicted tht subjects hd slightly better qulity diets the dy before strting in the study. This my be due to the interest of the subjects in helthy diets nd the nticiption of embrking on dietry study might hve mde them more wre of their eting ptterns. The differences were smll, lthough sttisticlly significnt, nd point to the potentil importnce of cpturing recent diet. Of the subjects who finished study prticiption, stisfction with being in the study ws high (Tble 6). It is interesting to note tht when sked bout wht ws the hrdest nd esiest prt of the study, by fr most of the replies indicted some spect of the dietry chnges. It therefore ppers tht chnging one's diet cn be difficult, but tht the perceived benefit from eting helthier foods is substntil. It is especilly encourging tht subjects would recommend the diet they were ssigned to nd intend to keep following it fter the study is over. Overll, the findings in this study indicte tht flexible sigmoidoscopy does not pper to be brrier for recruitment of high risk individuls but tht completing food records cn be. In ddition, individuls my chnge their diet when they re Tble 5 Chrcteristics of study completers nd non-completers given s mens nd SD or number nd percent. Chrcteristic Completer Non-completer n=93 n=27 Age, yers 54, 11 (rnge 24 82) 48, 14 (rnge 22 71) Femle gender 67, 72% 19, 70% BMI, kg/m 2 27, 4 (rnge 19 35) 28, 3 (rnge 22 35) Regulr spirin user 20, 21% 4, 15% Cucsin rce 83, 89% 22, 81% Mrried/committed 63, 68% 13, 48% College grdute 73, 78% 19 70%, Tobcco user 10, 11% 7, 26% History of denoms 27, 29% 6, 22% Fmily history of 58, 62% 19, 70% colon cncer Both risk fctors 8, 9% 2, 7% Vegetble intke, servings/ dy 2.99, , 1.25 The differences between completers nd non-completers were significnt using the two-smple t-test for ge t study entry (p=0.04) nd dietry intke of vegetbles (p=0.05). The other dietry vribles listed in Tble 4 were evluted s well nd none of these differed significntly by study completion sttus. Tble 6 Stisfction with study prticiption from questionnire dministered t the finl visit. Dt shown re men nd SD for nswers on scle of 1 to 5 with 5 being very much so nd 1 being not t ll. Chrcteristic bout to strt on dietry intervention study, which could ffect diet-responsive biomrkers. Although the intensive dietry chnges requested in this study were difficult to mke, subjects hd high stisfction with mking those chnges. Mediterrnen diets re populr, but the recruitment of subjects t high risk for colon cncer required n intensive effort to enroll 120 subjects over three yers. Future studies should budget stff time nd mrketing costs to ccommodte this need. Once subjects were enrolled, however, retention of subjects over six months ws resonbly good nd stisfction with the study ws high for study completers. Acknowledgments We thnk ll the individuls who volunteered their time for the Helthy Eting Study nd the students who helped with dt verifiction nd orgniztion: Megn Rook, Gry Schneider, Shony Reuven, Perry Ahn, Nncy Wener, Tiffny Yng nd Ofr Duchin. This study ws supported by NIH grnts RO1 CA nd P30 CA References Helthy Eting diet Mediterrnen diet I feel good bout being in the study 4.93, , 0.20 The diet ws esy to follow 4.47, , 0.54 I hve time to follow diet 4.74, , 0.61 The diet tkes more time thn my 3.02, , 1.23 usul diet Others t home mke it difficult 1.69, , 1.22 to follow the diet Being in the study ws stressful 1.58, , 0.97 Finishing is like weight being 2.20, , 1.03 lifted from my shoulders I like phone clls to minimize 4.44, , 0.83 ppointments I would recommend this diet to my 4.84, , 0.31 fmily nd friends I wnt to keep following this diet 4.91, , 0.36 fter the study is over Fctor (1.17), 0.31(0.95) 0.017(0.83), 0.16(1.29) Fctor (1.14), 0.28(1.86) 0.055(1.12), 0.07(1.12) Fctor (0.86), 0.22(1.16) 0.06(1.12), 0.44(1.41) The item responses were fctor nlyzed using the principl component extrction methods with vrimx rottion using ge s covrite. Fctor 1 contined four items: feel good bout being the study, diet ws esy to follow, hve time to follow diet, recommend diet to fmily nd friends. Fctor 2 contined diet tkes more time thn usul diet, being in the study ws stressful, nd finishing is like weight being lifted. Fctor 3 contined would recommend diet to fmily nd friends, wnt to keep following the diet, nd would like phone clls to minimize ppointments. Dt shown re men (SD), medin (inter-qurtile rnge). Bsed on the liner regression nlysis, none of these fctors were significntly different cross the two diet rms. [1] Americn Cncer Society. Colorectl cncer fcts nd figures specil edition Atlnt, GA: Americn Cncer Society; 2005.

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