Rosario Isasi|Peter W. Andrews|Jay M. Baltz|Annelien L. Bredenoord|Paul R. Burton|Ing Ming Chiu|Sara Chandros Hull|Ji Won Jung|Armin Kurtz|Geoffrey Lomax|Tenneille E. Ludwig|Michael McDonald|Clive Morris|Huck Hui Ng|Heather M. Rooke|Alka Sharma|Glyn Stacey|Curtis A. Williams|Fanyi Zeng|Bartha Maria Knoppers
Identifiability and Privacy in Pluripotent Stem Cell Research
McGill University|University of Sheffield|Ottawa Hospital|University of Ottawa|University Medical Center Utrecht|University of Bristol|National Health Research Institutes|National Institutes of Health|National Human Genome Research Institute|Korea National Institute of Health|Korea Disease Control and Prevention Agency|Berlin-Brandenburger Centrum für Regenerative Therapien|Seoul National University|California Institute for Regenerative Medicine|WiCell|University of British Columbia|National Health and Medical Research Council|Genome Institute of Singapore|Agency for Science, Technology and Research|Ministry of Science and Technology|Government of India|National Institute for Biological Standards and Control|Brunel University London|McGill University
data sharing essential element research however recent scientific social developments challenged conventional methods protecting privacy provide guidance determining data sharing thresholds human pluripotent stem cell research aimed wide range stakeholders including research consortia biorepositories policymakers funders data sharing essential element research however recent scientific social developments challenged conventional methods protecting privacy provide guidance determining data sharing thresholds human pluripotent stem cell research aimed wide range stakeholders including research consortia biorepositories policymakers funders discovery technologies generate induced pluripotent stem cell ipsc lines corresponding derivation large numbers lines research potential therapeutic use resulted rejuvenated interest biorepositories mckernan watt 2013mckernan r watt fm nat biotechnol 2013 31 875877crossref pubmed scopus 52 google scholar stacey et al 2013stacey gn crook jm hei ludwig cell stem cell 2013 13 385388abstract full text full text pdf pubmed scopus 54 google scholar biorepositories vital infrastructures providing primary material primary samples cell lines associated data research clinical translation today biorepositories serve also primary resource authenticated quality controlled ethically sourced human pluripotent stem cell hpsc lines robust banking networks enable global access wellcharacterized traceable hpscs essential prerequisite scientific reproducibility stacey et al 2013stacey gn crook jm hei ludwig cell stem cell 2013 13 385388abstract full text full text pdf pubmed scopus 54 google scholar availability resources presents wide range therapeutic opportunities however sharing also comes attendant responsibility protect donors research participants hereinafter participants privacy competing factors require striking delicate balance amount quality data collected precautions taken sharing information comprehensive data curation important cellline misidentification continues pervasive problem undermining scope authenticity research findings addition wellannotated genomic epigenomic data participants phenotypic demographic data facilitates disease modeling drug development contributes understanding genetic variation role normal cell behavior next generation sequencing ngs technologies combined bioinformatic data systems enable data analysis wide range participants facilitating translation cellbasedtherapies kreiner irion 2013kreiner irion cell stem cell 2013 12 513516abstract full text full text pdf pubmed scopus 9 google scholar mckernan watt 2013mckernan r watt fm nat biotechnol 2013 31 875877crossref pubmed scopus 52 google scholar forum discuss challenges establishing thresholds sharing publishing individualsummary data associated hpsc research review ensuing scientific socioethical legal implications propose framework criteria data sharing policies recommendations directed wide range stakeholders fundamental scientific data perceived community resource data sharing constitutes ethical scientific imperative recognized international funders scientific organizations across disciplines jurisdictions knoppers 2010knoppers bm embo rep 2010 11 416419crossref pubmed scopus 31 google scholar kaye 2012kaye j annu rev genomics hum genet 2012 13 415431crossref pubmed scopus 153 google scholar imperative underpinned principles reciprocity solidarity respect stakeholders data sharing envisaged tripartite responsibility data producers users funders isasi et al 2012isasi r knoppers bm andrews pw bredenoord colman hin le hull kim oj lomax g morris c et alinternational stem cell forum ethics working partyregen med 2012 7 439448crossref pubmed scopus 26 google scholar knoppers et al 2011knoppers bm isasi r benvenisty n kim oj lomax g morris c murray th lee eh perry richardson g et alinternational stem cell forum ethics working partystem cell rev 2011 7 482484crossref pubmed scopus 12 google scholar scientific integrity progress dependent sharing raw data researchers also ability widely disseminate research findings turn public trust earned maintained responsible stewardship latter entails protectingand possibly also promotingthe interests participants advancing societal benefits moreover trust requires respecting divergent interests balancing benefits risks proportionate appropriate manner rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar several scientific social developments prompting reconsideration imperative data sharing conceptualized implemented decreasing costs increasing accessibility ngs cloud computing along growing volume richness complexity genomic information available challenging individual privacy traditional methods designed manage secure data eg coding anonymization factors together reports ease reidentification scientific literature popular press contribute changing public attitudes meaning individual privacy attendant expectations fiduciary duties data stewards kaye 2012kaye j annu rev genomics hum genet 2012 13 415431crossref pubmed scopus 153 google scholar rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar empirical studies assess participants data sharing decisions attitudes demonstrate regarding clinical genetics research participants overall health informational altruists studies reassuring suggest inability guarantee privacy may deter individuals participating research rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar however also need consider mitigating actions ensure participants trust science example participants often wish involved decisionmaking concerns governance mechanisms safeguarding privacy addition studies show participants privacyutility tradeoff decisions vary real versus hypothetical scenarios kaye 2012kaye j annu rev genomics hum genet 2012 13 415431crossref pubmed scopus 153 google scholar hpsc research specifically emerging evidence participants broadly support data sharing even maintaining privacy concerns research needed systematically assess participants views dasgupta et al 2014dasgupta bollinger j mathews dj neumann nm rattani sugarman j cell stem cell 2014 14 912abstract full text full text pdf pubmed scopus 25 google scholar crucial juncture novel statistical methods associated tools allow drawing inferences possibly revealing identity individual participants biomedical research genomic information intrinsically selfidentifying source familial information recent study demonstrated reidentification possible even absence reference sample gymrek et al 2013gymrek mcguire al golan halperin e erlich science 2013 339 321324crossref pubmed scopus 741 google scholar several genomic studies also demonstrated wide range scenarios reidentifying participants biomedical research could possible triangulating multiple publicly available data sources eg census genealogy data obituaries voter registries etc established relying 75 individual statistically independent snp loci could enable unique individual identifiability gymrek et al 2013gymrek mcguire al golan halperin e erlich science 2013 339 321324crossref pubmed scopus 741 google scholar rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar reidentification ability protected data traced back participant occur directly indirectly deliberately unintentionally different means 1 directly matching genomic data reference genotype 2 deduction linking nongenetic databases eg health care forensic administrative genealogical etc matching genotype associated data eg gender age disease status etc 3 inference profiling genomic data dna analysis eg gender blood type etc consequently individual identifiability currently present incremental levels overtly identifiable potentially identifiable rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar gymrek et al 2013gymrek mcguire al golan halperin e erlich science 2013 339 321324crossref pubmed scopus 741 google scholar kaye 2012kaye j annu rev genomics hum genet 2012 13 415431crossref pubmed scopus 153 google scholar generalizability abovementioned methods tools continues evaluated evidencebased risk reassessments continue debated clear concepts identifiability privacy shifting expectations stakeholders proportional realistic risk assessment due consideration given existence multiple data resources potential data users malicious intruders also different data environments whole extend well beyond research context privacy risk assessments also situated society social media directtoconsumer genetic testing omnipresent knoppers 2010knoppers bm embo rep 2010 11 416419crossref pubmed scopus 31 google scholar manner individuals broadly openly sharing personal information genomic otherwise well family members information either directly association factors increase likelihood participant reidentification expanding range data resources publicly available used combination data sources reidentify individuals create vulnerabilities governance mechanisms decrease effectiveness data security measures challenge protections privacy confidentiality thereby provide opportunity participant reidentification gymrek et al 2013gymrek mcguire al golan halperin e erlich science 2013 339 321324crossref pubmed scopus 741 google scholar rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar reasons relying solely traditional methods based informed consent data coding anonymization irreversibly stripping identifiers naive insufficient protect participants privacy kaye 2012kaye j annu rev genomics hum genet 2012 13 415431crossref pubmed scopus 153 google scholar sophisticated security measures combination sanctions deliberate breaches confidentiality required keep pace technological developments knoppers et al 2011knoppers bm isasi r benvenisty n kim oj lomax g morris c murray th lee eh perry richardson g et alinternational stem cell forum ethics working partystem cell rev 2011 7 482484crossref pubmed scopus 12 google scholar pivotal concern regarding identifiability potential personal health information associated specific individual possible harms discrimination eg employment insurance stigmatization stress anxiety kaye 2012kaye j annu rev genomics hum genet 2012 13 415431crossref pubmed scopus 153 google scholar harms need confined individual could also extended community subpopulation participant belongs based disease condition ethnicity familial relations needless say unintended deliberate misuse disclosure personal information due participant reidentifiability breaches trust established researchers participants therefore risks harms restricted solely participants also present data stewards researchers entire scientific enterprise rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar knoppers et al 2011knoppers bm isasi r benvenisty n kim oj lomax g morris c murray th lee eh perry richardson g et alinternational stem cell forum ethics working partystem cell rev 2011 7 482484crossref pubmed scopus 12 google scholar also emphasized however present time concerns reidentification genomic data research context largely hypothetical knownpublished reports breaches confidentiality resulting actual harm participants genetic research published examples using statistical methods reidentify genomic data proofs concept rather malicious uses data gymrek et al 2013gymrek mcguire al golan halperin e erlich science 2013 339 321324crossref pubmed scopus 741 google scholar rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar given hesc line reflects contributions two genetically different individuals geneticgenotype data arising hesc line unique embryocell line directly attributable individual donor reason possibility donor reidentification based solely upon genotype hesc line remains extremely remote however hescassociated data would correspond directly genotype individual donor donors information gleaned using diverse molecular analyses could medical social significance donors related individuals moreover cases interpretations certain genetic data derived numerous loci eg ethnicity combined laboratory origin partial genotype information putative donor donors could sufficient donors identify identified others triangulation public information knoppers et al 2011knoppers bm isasi r benvenisty n kim oj lomax g morris c murray th lee eh perry richardson g et alinternational stem cell forum ethics working partystem cell rev 2011 7 482484crossref pubmed scopus 12 google scholar isasi et al 2012isasi r knoppers bm andrews pw bredenoord colman hin le hull kim oj lomax g morris c et alinternational stem cell forum ethics working partyregen med 2012 7 439448crossref pubmed scopus 26 google scholar contrast hesc lines ipscs contain donorspecific dna gene insertion reprogramming process results minor changes dna changes methylation patterns geneticgenomic data arising context remains virtually identical donor consideration given circumstances potential reidentifiability exacerbated example context donors affected rare disorders due small population size uniqueness genotype media publicity could allow discovery personal data linked genetic information isasi et al 2012isasi r knoppers bm andrews pw bredenoord colman hin le hull kim oj lomax g morris c et alinternational stem cell forum ethics working partyregen med 2012 7 439448crossref pubmed scopus 26 google scholar scientists research consortia biorepositories funding bodies envisage system data sharing grounded principles good governance ensures fair balance individual interests public benefits system rely establishing different thresholds data sharing minimize chances triangulation particular data set data sets could facilitate reidentification participant kaye 2012kaye j annu rev genomics hum genet 2012 13 415431crossref pubmed scopus 153 google scholar thresholds situated along continuum overtly identifiable potentially identifiable datasamples rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar subject ongoing reassessment reflect pace scientific discoveries consider changing public attitudes determine contemporaneous concerns participants regards meaning individual privacy attendant expectations regarding scope fiduciary duties datasample custodians moreover goal open science principles transparency autonomy beneficence argue favor system broad informed consent sharing genotypic phenotypic data hpsc lines subject appropriate governance knoppers et al 2011knoppers bm isasi r benvenisty n kim oj lomax g morris c murray th lee eh perry richardson g et alinternational stem cell forum ethics working partystem cell rev 2011 7 482484crossref pubmed scopus 12 google scholar isasi et al 2012isasi r knoppers bm andrews pw bredenoord colman hin le hull kim oj lomax g morris c et alinternational stem cell forum ethics working partyregen med 2012 7 439448crossref pubmed scopus 26 google scholar robust consent process entails empowering participants make risksbenefits assessment participation also requires improving genetic literacy knoppers 2010knoppers bm embo rep 2010 11 416419crossref pubmed scopus 31 google scholar kaye 2012kaye j annu rev genomics hum genet 2012 13 415431crossref pubmed scopus 153 google scholar rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar end consent process explicitly address datasharing scenarios implications protection participants privacy confidentiality disclose reasonably foreseeable likelihood reidentification without overstating likelihood risks materializing also acknowledging nonabsolute effectiveness available protections propose framework criteria data sharing policies funding bodies scientists research consortia biorepositories policy should1be consistent participant consent conform applicable laws ethics within consent process limitations data protection measures disclosed2establish conditions releasing data include binding enforceable commitment researchers data custodians share data unauthorized third parties use data alone combination data sets either attempt create conditions reidentification individual participant end oversight mechanisms established3manage data associated given hpsc line eg genomic epigenomic phenotypic demographic available based proportional assessment risks individual identifiability tailored nature cell line derivation eg hescs versus ipscs cautious approach taken sharing raw sequence reads eg whole genomes full exomes short tandem repeats strs snps identity profiles given include sensitive personal information directly identifiable would facilitate reidentification otherwise deidentified data however research laboratories encouraged share str profiles cell lines bona fide researchers biorepositories identity data eg strs snps etc shared strict confidence solely purposes confirming cell line identity quality control purposes resolving cases cell line crosscontamination4stipulate appropriate sanctions breach authorized handle data5in conformity recommendation 3 make available sensitive personal data associated hpsc line bona fide researchers provided protocol isconsistent widely recognized good research practice applicable legal ethical requirementsaimed generating new knowledge understanding using rigorous scientific methodsintended publication sharing research findings scientific community without undue restrictions andreviewed independent oversight entity field hpsc research evolves changes potential reidentifiability participants data stewards should1make appropriate adjustments data sharing arrangements line considerations and2avail research concerns hpsc participants use information guide data sharing practices methods governance mechanisms ensure absolute protection participant identity rodriguez et al 2013rodriguez brooks ld greenberg jh green ed science 2013 339 275276crossref pubmed scopus 95 google scholar kaye 2012kaye j annu rev genomics hum genet 2012 13 415431crossref pubmed scopus 153 google scholar currently participant reidentification rare proportionate approach privacy context data sharing construed based reasonably foreseeable risks thereby distinguishing perceived real risks approach rely worst case hypothetical scenarios relate situations possibility identifiability remains negligible knoppers 2010knoppers bm embo rep 2010 11 416419crossref pubmed scopus 31 google scholar importantly subject ongoing reassessment reflect evolving scientific advances well changing public attitudes sometimes react hypothetical scenarios dasgupta et al 2014dasgupta bollinger j mathews dj neumann nm rattani sugarman j cell stem cell 2014 14 912abstract full text full text pdf pubmed scopus 25 google scholar proportionate criteria determining risks real remote identifiability needed avoid unnecessarily overexpanding privacy regulations could hinder scientific progress moreover drafting criteria question whether informationrich societies goal complete deidentifiability avoid privacyrelated risks realistic laudable goal knoppers 2010knoppers bm embo rep 2010 11 416419crossref pubmed scopus 31 google scholar amount legal protection ethical safeguards eliminate risks enforceable sanctions eg withholdingterminating actualfuture funding participation research projects disclosing misconduct funding bodies stakeholders misuse data realistic useful legal tools furthermore use transparent terminology coded refer deidentified cell lines databut instead acknowledges small potential risk reidentificationmay serve provide potential participants accurate basis making informed decisions whether assume risks permit cells data used research grateful international stem cell forum stem cell network canada funding support opinions expressed authors alone