Kelly M. Herremans|Andrea N. Riner|Robert A. Winn|José G. Treviño
Diversity and Inclusion in Pancreatic Cancer Clinical Trials
Florida College|University of Florida|Florida College|University of Florida|Virginia Commonwealth University|Virginia Commonwealth University
pancreatic cancer defined lethality disease estimated 5year survival rate 9 increasing incidence projected soon become second leading cause cancer deaths united states1rahib l smith bd aizenberg r et alprojecting cancer incidence deaths 2030 unexpected burden thyroid liver pancreas cancers united statescancer res 2014 74 29132921crossref pubmed scopus 3359 google scholar pancreatic cancer affect populations equally significant health disparities exist race ethnicity gender last 2 decades black individuals persistently 19 higher incidence pancreatic cancer compared racial groups2seerexplorer interactive website seer cancer statistics surveillance research program national cancer institutehttpsseercancergovexplorergoogle scholar present younger ages advanced disease moreover black patients pancreatic cancer experience higher ageadjusted mortality rate compared racial groups 133 vs 110 per 100000 population racialethnic groups combined native american patients also higher rates death pancreatic cancer estimated 5year survival rate 672seerexplorer interactive website seer cancer statistics surveillance research program national cancer institutehttpsseercancergovexplorergoogle scholar contrast hispanic patients diagnosed pancreatic cancer longest median overall survival compared ethnic groups3riner underwood pw yang k et aldisparities pancreatic ductal adenocarcinomathe significance hispanic ethnicity subgroup analysis treatment facility clinical outcomescancer med 2020 9 40694082crossref pubmed scopus 3 google scholar disparities entirely accounted comorbidities socioeconomic status access highquality health care alone suggesting biologic processes may partially responsible4arnold ld patel av yan et alare racial disparities pancreatic cancer explained smoking overweightobesitycancer epidemiol biomarkers prev 2009 18 23972405crossref pubmed scopus 77 google scholar although critical address systemic injustices institutional racism disadvantages faced minority populations ancestral differences tumor biology cannot overlooked recently increased focus applied exploring racial ethnic differences patient tumor biology multiomics approach oncologic disparities identified based differences germline somatic mutations molecular subtypes tumor immune response epigenetics microbiota5vick ad hery dn markowiak sf et alclosing disparity pancreatic cancer outcomes closer look nonmodifiable factors potential use treatmentpancreas 2019 48 242249crossref pubmed scopus 0 google scholar black patients pancreatic cancer likely kras somatic mutations her2 protein overexpression compared white patients6pernick nl sarkar fh philip pa et alclinicopathologic analysis pancreatic adenocarcinoma african americans caucasianspancreas 2003 26 2832crossref pubmed scopus 41 google scholar germline lossoffunction mutations brca 12 genes cdkn2a tumor suppressor genes also common patients african ancestry patients germline brca cdkn2a mutations increased risk pancreatic cancer may exhibit different treatment responses targeted therapies7golan kindler hl park jo et algeographic ethnic heterogeneity germlinej clin oncol 2020 38 14421454crossref pubmed scopus 21 google scholar8mcwilliams rr wieben ed chaffee kg et algermline rare coding variants risk pancreatic cancer minority populationscancer epidemiol biomarkers prev 2018 27 13641370crossref pubmed scopus 9 google scholar given racial ethnic differences pancreatic cancer tumor biology unlikely patients exhibit similar outcomes trialed therapeutics address inequities congress issued final rule clinical trials registration results information submission 42 cfr part 11 requiring race ethnicity reporting clinicaltrialsgov clinical trial participants9clinicaltrialsgov clinicaltrialsgov backgroundhttpsclinicaltrialsgovct2aboutsitebackgroundgoogle scholar given implementation requirements sought assess current state diversity inclusion investigating trends demographic data reporting assessing impact diversity pancreatic cancer clinical trials hypothesized racial ethnic minority patients pancreatic cancer continue underrepresented despite federal requirement transparent trial demographic reporting consequence participation underrepresentation clinical trials likely perpetuates health disparities found pancreatic cancer treatment outcomes evaluate trends diversity inclusion comprehensive review pancreatic cancer clinical trials performed using us national library medicines clinicaltrialsgov database search criteria included pancreatic cancer pancreatic carcinoma subtopics included pancreatic neoplasm pancreas cancer cancer pancreas cancer pancreas pancreatic tumors carcinoma pancreas neoplasm pancreas search filtered include adult study participants 18 years age interventional clinical trial studies trials limited results comprises study results information included study record study results tab study phases included study phase labeled applicable na describes device behavioral interventions defined us food drug administration fda database queried december 21 2020 initial search yielded 337 clinical trial results one hundred thirty clinical trials excluded conducted outside united states n 44 included cancer types n 83 pancreatic pathologies n 3 exclusion criteria selected cleanly analyze pancreatic cancer clinical trials within united states descriptive statistics recorded provided study results results crossreferenced formally linked publications clinicaltrialsgov well pubmedgov using trial registry numbers secondary source identification field results reported clinicaltrialsgov gender female male ethnicity hispanic latinx hispanic latinx unknown reported race american indian alaska native asian native hawaiian pacific islander black african american white 1 race unknown reported lack racial ethnic demographic reporting 2005 2007 data excluded longitudinal analysis n 1 clinical trial sponsors categorized primary sponsor type universitycancer center national cancer institute nci pharmaceuticalsbiotech private hospitals enrollment fraction ef calculated trial subgroup population term ef initially described murthy et al10murthy vh krumholz hm gross cp participation cancer clinical trials race sex agebased disparitiesjama 2004 291 27202726crossref pubmed scopus 1315 google scholar defined number clinical trial participants divided us incidence cancer race ethnicity gender subgroup wilcoxon rank sum tests used determine whether center distribution ef ratios among trials differed 1 incident cases pancreatic cancer collected north american association central cancer registries 2013 2017 ageadjusted 2000 us standard population11goldberg dw kohler b kosary c texas naaccr nci geocoding service 2021httpsgeonaaccrorggoogle scholar pancreatic cancer incidence unavailable multiracial unknown racial ethnic subgroups ef analysis could calculated analyses performed using r statistical software package v402 r foundation statistical computing twohundred seven pancreatic cancer clinical trials comprising 8429 pooled participants included results reported 2005 2020 timespan race ethnicity reported 493 347 studies respectively whereas 99 studies reported participants gender supplementary table 1 reporting participant race ethnicity data however improved substantially time p 0001 figure 1a 2019 100 trials reported data race 733 trials reported data ethnicity 2020 100 race ethnicity data reported although 2 trials meeting inclusion criteria publicly reported results time data analysis data represent encouraging trend toward improved sponsor reporting race ethnicity data last decade despite positive trajectory reporting race ethnicity data nonwhite hispanic patients remain markedly underrepresented pancreatic cancer clinical trials white patients made majority 847 ef 105 p 002 pancreatic cancer clinical trial participants whereas black 82 ef 043 p 002 asianpacific islander 24 ef 0 p 0001 american indian alaskan native 03 ef 0 p 0001 hispanic 6 ef 047 p 0001 patients disproportionately missing table 1 trial participants also likely male 548 ef 107 p 0006 female 452 ef 093 p 001 indicated significantly low median ef underrepresentation nonwhite hispanic patients result trials rather systemic underrepresentation across pancreatic cancer clinical trialstable 1diversity pancreatic cancer clinical trial participantsparticipant demographicsno cases proportion incident casesaincident cases 20132017 ageadjusted 2000 us standard population median efbmedian ef individual trial demographic data reportedp valuecwilcoxon rank sum tests determined distribution ef ratios different 1race 102 trials race data 4374 participants white3704 847823105002 black360 821240430001 asianpacific islander105 243300001 american indianalaska native11 030400001 multiracialdincident cases reported north american association central cancer registries multiracial unknown subgroups32 07nanana unknowndincident cases reported north american association central cancer registries multiracial unknown subgroups162 37nananaethnicity 73 trials ethnicity data 2981 participants nonhispanic2711 909915102271 hispanic180 60850470001 unknowndincident cases reported north american association central cancer registries multiracial unknown subgroups90 30nananagender 204 trials gender data 8278 participants female3744 452484093001 male4534 5485141070006note na describes device behavioral interventions defined us food drug administrationa incident cases 20132017 ageadjusted 2000 us standard populationb median ef individual trial demographic data reportedc wilcoxon rank sum tests determined distribution ef ratios different 1d incident cases reported north american association central cancer registries multiracial unknown subgroups open table new tab note na describes device behavioral interventions defined us food drug administration additionally nonwhite hispanic female patients pancreatic cancer underrepresented across nearly phases clinical trials supplementary table 2 fact studies limited pancreatic cancer clinical trials united states black american indianalaskan native patients documented phase iii clinical trials asianpacific islander american indianalaskan native patients reported phase iv clinical trials based ef nonwhite hispanic patients pancreatic cancer underrepresented clinical trials sponsored universities cancer centers pharmaceutical biotech companies nci supplementary table 3 female patients also underrepresented sponsor types except nci although progress made demographic reporting figure 1a trends participant racial ethnic diversity remained relatively unchanged 2008 2020 figure 1b c data indicate nonwhite hispanic female patients pancreatic cancer continue disproportionately represented across pancreatic cancer clinical trials relative disease burden underrepresentation spans clinical phases sponsors meaningful improvement participant diversification last decade lack diversity found pancreatic cancer clinical trials salient example broader disparities diversity inclusion found across clinical trials enrollment disparities cancer clinical trials first noted murthy et al10murthy vh krumholz hm gross cp participation cancer clinical trials race sex agebased disparitiesjama 2004 291 27202726crossref pubmed scopus 1315 google scholar evaluated racial ethnic representation breast colorectal lung prostate cancer clinical trials 2000 2002 within nci clinical trial cooperative group noted racial ethnic minorities women elderly less likely enroll cancer clinical trials subsequently duma et al12duma n vera aguilera j paludo j et alrepresentation minorities women oncology clinical trials review past 14 yearsj oncol pract 2018 14 e1e10crossref pubmed scopus 83 google scholar explored racial ethnic gender disparities common cancer clinical trials found decrease recruitment minority patients 2003 2016 well low recruitment black hispanic female patients cancer clinical trials supporting findings study focused prostate cancer clinical trials rencsok et al13rencsok em bazzi la mckay rr et aldiversity enrollment prostate cancer clinical trials current status future directionscancer epidemiol biomarkers prev 2020 29 13741380crossref pubmed scopus 15 google scholar found participants white men moreover african caribbean countries predominantly black populations represented 3 prostate cancer clinical trials 1987 201613rencsok em bazzi la mckay rr et aldiversity enrollment prostate cancer clinical trials current status future directionscancer epidemiol biomarkers prev 2020 29 13741380crossref pubmed scopus 15 google scholar underrepresentation racial ethnic minority populations also found surgical oncology trials clinical trials leading fda approval oncology drugs14stewart jh bertoni ag staten jl et alparticipation surgical oncology clinical trials gender raceethnicity agebased disparitiesann surg oncol 2007 14 33283334crossref pubmed scopus 170 google scholar15loree jm anand dasari et aldisparity race reporting representation clinical trials leading cancer drug approvals 2008 2018jama oncol 2019 5e191870crossref pubmed scopus 88 google scholar last 3 decades federal initiatives aimed increase accrual racialethnic minority patients clinical trials 1990 minoritybased community clinical oncology program founded goal increase ncis clinical trial network minority populations decrease racialethnic disparities16mccaskillstevens w mckinney mm whitman cg et alincreasing minority participation cancer clinical trials minoritybased community clinical oncology program experiencej clin oncol 2005 23 52475254crossref pubmed scopus 61 google scholar coupled national institutes health revitalization act 1993 fda modernization act 1997 initial progress made improve heterogeneity clinical trial participants unfortunately despite early progress national accrual minority patients clinical trials remained poor last 2 decades17chen ms lara pn dang jh et altwenty years postnih revitalization act enhancing minority participation clinical trials empact laying groundwork improving minority clinical trial accrual renewing case enhancing minority participation cancer clinical trialscancer 2014 120 10911096crossref pubmed scopus 180 google scholar spurred section 907 fda safety innovation act 2012 fda recently instituted multiple initiatives improve representation racial ethnic minorities clinical trials includes fdas action plan enhance collection availability demographic subgroup data18us food drug administrationenhancing diversity clinical trial populationseligibility criteria enrollment practices trial designs guidance industryhttpswwwfdagovregulatoryinformationsearchfdaguidancedocumentsenhancingdiversityclinicaltrialpopulationseligibilitycriteriaenrollmentpracticesandtrialgoogle scholar although implementation initiatives improved data collection availability evidence provided study indicates falling short achieving representation participant diversity improved challenges associated improving clinical trial diversity multifaceted complex although may simplified categorization based patients providers systemic challenges historically distrust quoted key challenge recruitment minority patients clinical trials distrust attributed historic atrocities exploitation minority populations particularly tuskegee syphilis study black men unknowingly given syphilis treatment withheld19hamel lm penner la albrecht tl et albarriers clinical trial enrollment racial ethnic minority patients cancercancer control 2016 23 327337crossref pubmed scopus 125 google scholar despite rightful distrust medical system black hispanic patients actuality equally willing white patients participate clinical trials20wendler kington r madans j et alare racial ethnic minorities less willing participate health researchplos med 2006 3 e19crossref pubmed scopus 518 google scholar factors disproportionally impact minority populations poor health literacy low socioeconomic status access care also largely affect willingness ability enroll clinical trial21clark lt watkins l pia il et alincreasing diversity clinical trials overcoming critical barrierscurr probl cardiol 2019 44 148172crossref pubmed scopus 89 google scholar although much emphasis placed overcoming patient factors literature suggests physician bias false perceptions prejudices may influence participation clinical trials study van ryn burke22van ryn burke j effect patient race socioeconomic status physicians perceptions patientssoc sci med 2000 50 813828crossref pubmed scopus 938 google scholar physicians likely believe black patients less intelligent less likely comply medical treatment result physicians recommend clinical trials minority patients concerns compliance trial protocols notably racialethnic disparities negated patients given equal opportunity explicitly offered participation clinical trial23kehl kl arora nk schrag et aldiscussions clinical trials among patients newly diagnosed lung colorectal cancerj natl cancer inst 2014 106 dju216crossref scopus 6 google scholar moreover 23 practicing oncologists black african american 58 practicing oncologists hispanic likely largely impacting trial referral practices patient trust24american society clinical oncologyfacts figures diversity oncologyhttpswwwascoorgnewsinitiativescurrentinitiativesdiversityoncologyinitiativefactsfiguresgoogle scholar systemic barriers clinical trial design infrastructure also may limit minority patient participation include limited number trials resources poor community engagement strict trial eligibility criteria patients racial ethnic minority backgrounds also likely receive care institutions insufficient resources21clark lt watkins l pia il et alincreasing diversity clinical trials overcoming critical barrierscurr probl cardiol 2019 44 148172crossref pubmed scopus 89 google scholar additionally strict eligibility criteria often exclude many minority patients interested participating clinical trials study adamscampbell et al25adamscampbell ahaghotu c gaskins et alenrollment african americans onto clinical treatment trials study design barriersj clin oncol 2004 22 730734crossref pubmed scopus 139 google scholar black patients rendered ineligible clinical trials secondary medical morbidities face challenges imperative equitably include racial ethnic minorities clinical trials emphasis improved communication trust education patients providers critical clinical trials reflect patient population serve disparities treatment outcomes perpetuated inclusion racial ethnic minority populations pancreatic cancer clinical trials take concerted intentional efforts toward diversification study several limitations warrant discussion exclusion trials including cancer types pancreatic pathologies may underestimate number patients pancreatic cancer participated diseaseagnostic phase ii clinical trials additionally including studies within united states may limit number phase iii phase iv clinical trials captured well global generalizability latter limitations allow us offer focused assessment relative us minority patient participation usbased pancreatic cancer clinical trials within north american association central cancer registries database race characterized white black asianpacific islander american indianalaska native assumption participants siloed neatly demographic category may overgeneralization true diversity us population despite limitations data suggest although demographic reporting improved time diversity clinical trial participants disproportionate disease burden pancreatic cancer findings emphasize persistent trend underrepresentation racial ethnic minority patients pancreatic cancer clinical trials representation minority patients pancreatic cancer clinical trials critical link oncologic innovation patient outcomes although prior initiatives experienced varying levels success propose future interventions need implemented multiple levels effectively include minority populations pancreatic cancer clinical trials improve diversity pancreatic cancer clinical trials propose following potential next stepspromotion inclusivity reevaluation strict eligibility criteria particularly disproportionally exclude patients racial ethnic minority backgroundsclinical trial accountability sponsor organizations support inclusion diverse patient populationimproved diversity providers coordinators conducting pancreatic cancer clinical trialscreation pancreatic cancer clinical trial environments free explicit implicit bias dedicated workforce trainingconduction pancreatic cancer clinical trials locations accessible racially ethnically diverse patient populationscontinued efforts toward patient advocacy public policy promote future change diversity inclusion pancreatic cancer clinical trials