Journal of Medicine and Philosophy

This article was downloaded by:[London, Alex John] [London, Alex John] On: 20 April 2007 Access Details: [subscription number 777159376] Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK

Journal of Medicine and Philosophy A Forum for Bioethics and Philosophy of Medicine Publication details, including instructions for authors and subscription information: http://www.informaworld.com/smpp/title~content=t713658121 Two Dogmas of Research Ethics and the Integrative Approach to Human-Subjects Research

To cite this Article: , 'Two Dogmas of Research Ethics and the Integrative Approach to Human-Subjects Research', Journal of Medicine and Philosophy, 32:2, 99 - 116 To link to this article: DOI: 10.1080/03605310701255727 URL: http://dx.doi.org/10.1080/03605310701255727

PLEASE SCROLL DOWN FOR ARTICLE

Full terms and conditions of use: http://www.informaworld.com/terms-and-conditions-of-access.pdf

This article maybe used for research, teaching and private study purposes. Any substantial or systematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden.

The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.

© Taylor and Francis 2007 Downloaded By: [London, Alex John] At: 19:33 20 April 2007 NJMP 0360-53101744-5019Journal of of MedicineMedicine and and Philosophy, Philosophy Vol. 32, No. 2, Feb 2007: pp. 0–0 elnUiest,15BkrHl,Ptsug,P,123 S.Emi:[email protected] Mellon University, 135 Baker Hall, Pittsburgh, PA, 15213, USA. E-mail: notto andtheimperative sacrif science of frontiers the advancing between inclinical research tension fundamental the managing of method dominant the as hasemerged equipoise clinical ics arein disarray. Over roughly the past twodecadesthe framework of eth- research of foundations the literature, recent of survey a from judge To TwoAlex DogmasLondon JohnResearch of Ethics DOI: 10.1080/03605310701255727 ISSN: 0360-5310 print/1744-5019 online Copyright ©Taylor &Francis Group, LLC JournalMedicine of andPhilosophy Address correspondence toAlexJohn London,Ph.D., Department ofPhilosophy, Carnegie exploitation, reasonable risk, therapeutic obligation. exploitation, Keywords: research. toclinical approach” “integrative the called alternative an outlinesof thebroad bysketching dogmas these ing ing these shortcomings,this article can betracedtotheiracceptance sh Moreover,important approach. alternatives, articulated recently traditional articulationsofth to common are dogmas these that argues Thisarticle researchers. is groundedinrole-relatedobli force moral whose endeavor onthis constraints mustimpose ethics The second dogma is that an acceptable framework forresearch research, as asocial activity, is Th ethics. ofresearch dogmas unfounded bytwo is perpetuated ethics of research foundations This article argues thatlingering uncertainty aboutthe normative Integrative ApproachtoHuman-Subjects Two DogmasofResearchEthicsandthe Carnegie MellonPi University, common good,rule, equipoise, non- ALEX JOHNLONDON I. INTRODUCTION , 32:99–116, 2007 Research an inherentlyutilitarian endeavor. e equipoise requirement and to and requirement e equipoise 99 e first dogma is that clinical first dogmaisthat e ofthese dogmas.After highlight- gations ofeitherphysiciansor ice theinterestsof presentindividuals ttsburgh, Pennsylvania,USA such as thenon-exploitation such as ortcomings of these approaches ortcomings illustrates the benefitsofreject- illustrates Downloaded By: [London, Alex John] At: 19:33 20 April 2007 prima facie restrictiveother andonthe permissi too too as side one on attacked been has requirement equipoise the Although groundedandtraced to,profession in,the (M duties” “fiduciary or 1974) (Fried, referr Also participants. tothose 1983) ipants aredeterminedby is which it to risks on the parameters to to effectuatethatgoal.According 100 tions to researchparticipants rests on ha theveryideathat researchers that 1983; Gifford, 1986; Hellman,2002). More research participants inthe participants process. research exploit don’t as they aslong behalf society’s on science sound conduct research subjects” (Brody &Miller, 2003, p.336), leaving researchers free to we jettisontheclaim that weare told, misconception, this wejettison Once endeavor. investigative, researchers have idea that subjectsof in order togather genera to individualpatients;itisinvestig clinical medicine,thepurposeof research are “logically incompatible” of the activity and that the goals of c of the goals the activityandthat of properly activity are co These criticsclaimthattheethical framework ofclinical equipoise represents thesolution to anon-problem. ond dogmaisthat an acce research, asa social activity, is an clinical that is dogma first the Briefly, ethics. ofresearch dogmas unfounded two by perpetuated is ethics of research foundations normative the believe that clinical rese this in (or, participants of research as thetherapeuticmi is known what clinical research. clinical th ofanalternative outlines broad the th ofrejecting thebenefits illustrate views. To these of acceptance their to traced be can approaches these of shortcomings important that Iargue section second Inthe approach. tation articulations traditional obligationsof either physiciansor researchers. role-related in isgrounded moral force whose enterprise this on constraints According to proponents of the the of proponents to According In the discussion that follows, I ar I follows, discussionthat In the In the firstsection below I show how these dogmas arecommon to idea that researchers owesuch determinedbythe of the equipoise requirement and to the non-exploi- arch is a therapeutic, ra a therapeutic, arch is the researcher’s “therape researcher’s the such fiduciary duties is suchfiduciaryduties ptable frameworkforrese researchers have“afi researchers Alex John London inherently utilitarian endeavor. The sec- ese dogmas, in the final section I sketch section final the in dogmas, ese case, the research ethics community) to community) ethics research case, the afundamentalphilo linical medicineand ate scientific hypotheses in populations in hypotheses scientific ate ve such therapeutic or fiduciary obliga- fiduciary or therapeutic such ve sconception—the mistaken propensity mistaken sconception—the lizable data. From this standpoint, the standpoint, this From data. lizable (Brody & Miller, 2003, p. 332). Unlike332). 2003, p. (Brody &Miller, iller &Weijer, 2003), theseduties are permissible to expose research partic- research permissible to expose gue thatthecurrent at I call the “integrative approach” to at I callthe“integrative nstraints that areappropriate foran proponents of this approach, the approach, ofthis proponents research is not to administerisresearch not treatment conceptual goals ed to as “duties of personal care” ofpersonal as“duties ed to recent critics,however, haveargued al role of researchers asphysicians. “non-exploitation” ve, such critics usually accept the usually ve, suchcritics duties to their subjects(Marquis, diagnosed as a variant of diagnosed asavariant duciary relationship with utic obligation”(Marquis, ther ther than ascientific or arch ethics must impose must arch ethics sophical confusion. sophical or the goals ofclinical uncertainty about approach, the approach, guiding purpose Downloaded By: [London, Alex John] At: 19:33 20 April 2007 and the idea that there is at least least at is there that idea the and Therefore, clinical (b) social The justificationfortheinstit (a) inference: sage from canbe Miller andBrody Thispas- 2003). &Brody, (Miller purpose” utilitarian pants—a frankly researchpartici- withcurrent fromexperimentation derived knowledge meansofscientific by patients offuture medicalgood to promotingthe Miller and Brody who argue that “clinicalresearchisdedicatedprimarily by expression its isgiven clearest thisidea inresearch ethics, tual roots historicalandconcep- deep ithas Although utilitarianenterprise. ently The firstdogmaof ethicsis research that researchisaninher- clinical e Definition of reasonablerisk: risksth (e) damentally utilitarian principle: common definition of reasonable risk and then diagnoses this rule asa fun- The second argument for (d) does not rely on (c). Instead, it begins with a Therefore, “abasicof clinical feature (d) tosocialactivitiessuch With respect (c) lowing additional premise (c): that derive sucha conclusion(b). (d)from The first makesuse ofthe fol- ethics research framework enterprise research ethics andisprimarilya claimabou To be clear, conclusion (b) is what social significance. usethe sound scientific methodsto investigate questions ofappropriate capacity to advance the common go designed to generate. designed to are sufficiently offsetby gains the in knowledge the research that is vidual trial participants are judgedto p. 162) 2007, &Brody, (Miller sequentialist.” p. 332) apply” to it. (Miller &Brody, 2003, p.22. See also Brody &Miller, 2003, and ofthe nature determines activity pose.” (Miller &Brody, 2007, p. 162). There is, however, a close relationship between the claim in(b) above for evaluating regu or forevaluating II. TWODOGMASOFRESEARCHETHICS . In fact,Miller and Brody endorse two distinct arguments . It is not necessarily researchis“aninstitution Two Dogmas of Research Ethics lating thatactivity. a fundamentalutilitarian componentto I am calling thefirs I am t the structure or purpose of the purpose of the structureor t seen as expressing thefollowing ution ofclinical re as clinical resear asclinical od ofcommunitymembers through researchethicsor con- isutilitarian at arenot offset by benefits to indi- the ethical standards that ought to that the ethical standards bereasonableifandonly ifthey a claimabouttheproper that serves a t dogma ofresearch ch, “the basicgoal ch, “the search lies inits utilitarian pur- ethical 101 Downloaded By: [London, Alex John] At: 19:33 20 April 2007 these requirements are notside-constraints the argumentsAs outlined above makehowever, clear, theof first three 2000). &Grady, Wendler, (Emanuel, persons for respect 7. review, and independent 6. that there is fair subjectselection, 5. consent, informed and free give subjects that 4. scientific validity, 3. theresearch that 2. are reas to subjects risks that 1. ensuring: in consists duty This non-exploitation. They hold, instead,researchers that havethe somewhat weaker duty of idea thatresearchers have fiduciary Miller and Brody’s preferred framework. dogm ofthis expression clearest the Althoughthepropon related obligations. research clinical on imposed be must ethics. research and research clinical of substrata utilitarian remaining functiontions asside-constraints,temperingand limiting thetheof reach that have acentral role in research ethics and thatthese duties and obliga- thatth social consensus What tarian core ethics. to research an inherentlyutilitarian acti isitself research clinical that the idea illustrate, and Brody as But, Miller ics. thosestronger utilitarianabout claims researchtemporaryliesethicshaving in debunked the moralfoundation for autonomy. abrogation ofothermoral the tojustify aresufficient and ethics in research consideration dominant the went further, however, by claiming thatconsiderations of social utility are views that endorsed most of the above claims. Those utilitarian views also utilitarian robustly more against argued (1977), Donagan and (1969) Jonas research ethics. Early philosophical pioneers inresearch ethics, such as implicit, that arewoven de (f) If it is the production of such valuable information that constitutes the that constitutes information valuable ofsuch If it is production the (f) 102 (g) Since advancing the common good in this way is a utilitarian enterprise autilitarian is way this in good common the advancing Since (g) social value of clinical social valueofclinical (from (b) above) then it follows that (d) is true. that (d)is follows then it (from (b)above) (a) above). (from good common the advance to order in necessary The second dogmaof research ethics isthatthe side constraints that On whatcommon isavery view, the central accomplishment ofcon- Each ofthesemake argumentsof above explicitaset views, often has social has social value and ere are numerous important duties and obligations values such as respect for individual welfareand individual for as respect such values eply into the history and theory ofcontemporary and theory history the into eply research thenreasonable research vity persists, asdoestheideathatthereisautili- vity persists, Alex John London onable (as defined in (e) above), has changed is the emergence of a of emergence isthe haschanged a, asimilar idearemainsoperativein draw their normative force from draw theirnormativeforce role- the proper structure for research eth- forresearch proper structure the obligations to research participants. research to obligations That is, Miller and Brody reject the reject Brody and Miller That is, that limit the pursuit of theutilitarian the pursuit that limit ents of clinical equipoise provide equipoise ofclinical ents risks arethosethat are Downloaded By: [London, Alex John] At: 19:33 20 April 2007 against gains in knowledge, andther off traded canbe welfare or health individual how fordetermining principle in thatthe thisca decision maker—in in rooted in the Hippocratic tradition,thisview is aformofconsequentialism Deeply consequentialism. ofwhat I willcallapatient-centered structure the Intere ability. ofhisorher to best the heal the advance to clinician individual the literature on equipoise. the clearestarticulation reason, this care. For of personal duty physician’s the with that is consistent participants that research research context. Thisconstraint takes the form of a requirement (roughly) inindividual onthetradeoffs straint the non-exploitation view, rather, isth (f), (g),and therefore (d) as well. Wh proponent of such an approach toendorse, not only (a) and (b), but also explicitly (e)itwoul acceptspremise poise requirement, known as “component analysis” (Miller &Weijer, 2004) fiduciary duties of clinicians constrain or check those goals. the how show to pains at are equipoise of proponents the research, clinical propositions in(a)and(b)abovead researcher andthegoalsofscientific ob between thetherapeutic tens the central oftenportray requirement research ethics while the formerrejectit.Proponents of the equipoise it is not ment fromthosethatreject ethics. of research enterprise tally utilitarian viewof the researcher’s role qua rese ofnon-exploita duty researcher’s of the Brody endorse (c)above,itappears thatwhat is distinctive in their account and Miller Since good. common the advance to order in of trialparticipants limitthe or directly curb be imposed onlyvoluntary on participants, for example, but theynot do good, is outlined in (1) above. The other constraints require thatsuch risks is endorsed by all re all by endorsed is Furthermore, withperhaps theexception each of(1), ofthese requirements theory. utilitarian legitimate any by endorsed be would requirements these goals ofclinicalresearch. goals and to express nece and toexpress goals What is distinctive in Miller and Brody’s view, therefore, is that the only the that is therefore, view, Brody’s and Miller in isdistinctive What As it is traditionally understood, the duty of personal care binds the binds care of personal duty the understood, traditionally itis As Moreover, because the dominant framework that employs the equi- require- equipoise the embrace that frameworks distinguishes What asonable frameworks of the second dogma of re (b). Hence, their acceptance of the second dogma second ofthe acceptance their Hence, (b). Two Dogmas of Research Ethics extent of the potential sacrifices that can beasked can that sacrifices extent of thepotential Rather, they serve partly to Rather, theyservepartly must receive a level of care ssary conditionsforthei ligation or fiduciary duties ofthe individual that the latter embrace the first of thefirst dogma thelatterembrace that efore the advancement of the common ofthe advancement the efore archer, and of research as a fundamen- and ofresearchas archer, se the individual clinician—is obligatedthe individual clinician—isse at distinguishes theseat distinguishes approaches from research. Rather than denying that the that than denying Rather research. equatelythe propergoals express of d not generate inco generate not d eir imposition of a further moral con- moral ofafurther eir imposition stingly, however, thisduty itself has welfare thatcanbejustifiedinthe tion, therefore, is derived from their from isderived therefore, tion, th interests ofthe interests th ion in research et for research ethics. for research r achievement.r Assuch, search ethicsappearsin define those utilitarian those define within a clinical trial individual patient individual nsistency forthe hics as a conflict hics as 103 Downloaded By: [London, Alex John] At: 19:33 20 April 2007 tions for treating tions fortreating the condition. patient’s ther relative the concerning uncertainty if clinical researchbegins of state the advance to duty the and quentialism: theduty to of conse- forms two these reconcile to effort an as seen be therefore can theco than with patient, rather lar particu- the of interests best individual the with identified is good the that in to theactthatmaximizes the perform 104 dogmas of research ethics. two Iamcalling what to back traced be can that shortcomings serious face fram and approach exploitation non The in the larger expert medical community. medical expert larger the in Freedman (1987, 1990), in contrast, claims that the uncertainty should reside orresearcher. clinician individual ofthe mind in the reside must uncertainty (1974) and others (Peto et al., 1976; Chard &Lilford, 1998) arguethe that Fried uncertainty? relevant morally the is uncertainty whose i.e., located, be three questions(London, 2007). First,wherethe relevant must uncertainty ment can be distinguished by the answers that they give to thefollowing the set of interventions. co medical expert the in so exists according towhichuncertainty prospect. Freedman, in contrast,argu tage of eachtheavailabletreatm advan- therapeutic net relative the to which according threshold epistemic afragile adopt to seem others and Fried isdisturbed? it when and tainty able clinical resear obtain, or that it will be so fragile when rarely so will condition equipoise the that charge the is First requirement. responsible fortwin challengesthatequipoiseframeworksthe to adopt and benefitsthey that pose individual to subjects. risks the to relative not and policy, of amatter as general, in interventions therelative about cal community ular interests. Others argue that equipoise deals with the views of the medi- partic- hisor her and patient individual the on focus should uncertainty the often notexplicitly clarified butitam Forpresent our purposes,different Second, what is th Third, what is the proper focus of In slightly different ways, the second dogma of research ethics is III. LIMITATIONSOFTHETWODOGMAS ch fromgeneratingsocially valuable data. Thischargeof e epistemic threshold that defines the state of uncer- advance the best interests of the individual patient individual ofthe interests best the advance mmunity about therelative in,andisdesignedtoel Alex John London mmon good. The equipoise requirement equipoise The good. mmon medical science can both be discharged ounts to thefollowing. Some hold that ent options must be an equal bet in bet anequal be must options ent good. It ispatient–centered, however, es for a robust epistemicthreshold es forarobust the uncertainty? This requirement is Thisrequirement theuncertainty? therapeutic ofthe therapeutic merits set of it does obtain, that does obtain, it apeutic apeutic merits ofthe interven- trial long asthereisalackofconsensus eworks that rely on equipoise each equipoise on rely that eworks versions oftheequipoise require- iminate, an honest stateof iminate, an therapeutic benefits of benefits therapeutic it prohibits valu- itprohibits Downloaded By: [London, Alex John] At: 19:33 20 April 2007 their individualpatients physician in theclinical context. Each beappear to obligatory. First,duty the ofpersonal care binds individual the personal care, thenat of duty physician’s the from derived are ofresearchers obligations moral ‘acc patients their to benefit physicians duty of personal care when it says that, “The Hippocratic Oath requires paternalistic. overly several reasons. The one thatI defend results fromthe physician’stherapeuti tion. The second point Iwant to make ommend) the best option outset ofthe of feasibleoptions, where best is nality according to which agents are re also seemstobe required by themost commonnormative standard ofratio- fo optimaltreatment or best mend the commonlycare is taken toimposeanobligationthe on physician recom- to First, asaformofpatient-centeredconsequentialism, ofduty the personal one, maya fragilealso should be patient. individual of the interests health the on focus must uncertainty cian’s duty isowedtotheindividualpatien recommendthata patient enter intoa the relativenetther thatthe requires even led some proponents of that view ofthat proponents some led even has and equipoise clinical Freedman’s of criticisms significant motivates of thepartic and focusontheinterests mustrelevant locatethe uncertaintythe inof mind the individualresearcher groundedthe in physician’s therapeutic obligation, thenthat requirement The first isthat The first if thenormative her. or him for best are tions clinician may have formed a considered option about which of the interven- trialspermits clinical to insensitive totheinterestsofparticular dogma of research he what for threshold epistemic robust ethicsmore a adopted and community medical expert larger the to uncertainty of liesth avoid To threshold. fragile epistemic behind theproposed treatmentoptionsthe pa for charge that about uncertain tobe ual researcher Freedman’s individ- the require that equipoise of versions against telling ismost fragility view is The The providesa Report Belmont standa The thirdelement ofthe above view,the that epistemic threshold For the purposes ofthe present discussion I want to make two points. individual clinician orresearcher apeutic merits of the available interventions in order to least two components of the equipoise oftheequipoise least two requirement components begin, orto continue, even though the individual according to their best judgment. As a result, Asaresult, this according totheirbest judgment. Two Dogmas of Research Ethics force for the equipoise requirement is requirement equipoise the for force ppear to be obligatory for two reasons. t it appears obligatory that thephysi- t itappearsobligatory physician is charged with benefiting with charged is physician calls “clinical equipoise.” The second The equipoise.” “clinical calls the net therapeutic the nettherapeutic advantage of the quired to choose (orin thiscase, rec- ording to their best judgment.’” Ifthe judgment.’” best to their ording r the individual patient. Second, this c obligation should be rejected for is result,Freedman here isachargethatsuchviewsare clinical trial participants becauseit rticular patient, and which adopta patient, and rticular ular patient. This, I argue,is what clinical trial. Second, because this to shifttheirpositi is that the viewequipoise of that rd expression of the physician’s mustbe uncertain about shifted the locus shifted the on in this direc- this in on 105 Downloaded By: [London, Alex John] At: 19:33 20 April 2007 way to go. She therefore advises advises way go. therefore to She his treatment his treatment decision, 2003): &Kadane, London 2006; London, Evans& 2007; 2006, (London, flict con- clinical what Icall of example following the this, consider To see research ethics. in paternalism ofmedical vestige anunjustified embody views thatsuch is however, trial, aclinical in enrolled canbe patient individual the requires that view any individual patient. tothe obligations fiduciary physician’s the to responsive asinsufficiently it isseen because poise and Fried’s version of equipo of version Fried’s and poise recent article, Weijer and Paul B. Mill in a Yet, threshold. epistemic a robust requires and community expert Freedman’s clinical equipo that view the defended has he and requirement equipoise ofthe nents patient? of this particular option treatment available of the Which question: clinician’s the address not does and interventions ofvarious merits which the community of expertclinicians is uncertain about the therapeutic shouldrejected be precisely because stood. Similarly, DeborahHellman (200 grounds that itis not consistent with the on equipoise clinical reject then but consider (1998) Lilford and Chard that the duty of personal care in th view ofrationality motivating must have thisbetweenis them. difficultoverstateIt theto rolethe importance ofthis of structure tothe same expected utility—then the physician will not be in equipoise it. For instance,Unless the available options arean equal betin prospect—unless they have outcome whose option asthe understood 106 mends interventions mend interventions opposite view from C view from opposite patients sivefiduciary tothe obligations those who argue thatFreedman’s clinical equipoise isinsufficiently respon- to aconcession represent to appears incomplete are views these selves ject should be enrolled in thattrial. sub- an individual whether determining for standard the articulates version and Fried’s trial a clinical initiate to isappropriate it which under conditions Weijer, 2003). The reason isthat Freedman’s clinical equipoise lays out the Patent or is eitherrevised rejected view each of thesecases, Freedman’s In Finally, Charles Weijer is one of the most articulate and sensible propo- recognize to appear equipoise clinical of proponents and critics Both . i suffers from condition D and visits clinician C clinician visits and D condition from suffers 2 for this patient but C but patient this for 1 . C i 1 visits another clinician C clinician another visits , recommending s , recommending 1 recognizes that others in the field might recom- ise locates therelevant Alex John London i that physicians havetotheir that physicians e fragility argument against taking s againsttaking Weijer and Miller’sWeijer er arguethatFreedm the duty ofpersonal care, so under- One reason to be dissatisfiedwith tobe reason One iseincomp arenot s will best advance the health needs health the advance s willbest it articulates the conditions under conditions it articulates the clinician to be uncertain before a before uncertain be to clinician 2) argues that clinical equipoise clinical that 2) argues has this highest expected utility. 2 1 as the optimal treatment and treatment optimal the as believes that thisis the wrong 2 who has the diametrically uncertaintyin the larger 2 . Seeking to be sure of against equipoise. against claim that inthem- an’s clinical equi- clinical an’s atible (Miller & 1 who recom- individual Downloaded By: [London, Alex John] At: 19:33 20 April 2007 himself to be assigned to s dently prefer one to another, why would it not be permissible for permissible be not it would why another, to one prefer dently from participating in a clinical trial between s between trial aclinical in participating from participation to research to offer permissible be not that equipoisemindtheinof theindividual must exist clinician thenit will is research clinical in forparticipation condition anecessary that holds ment therefore, that both s both that therefore, community isuncertain about which treatment isbesta for patient, and, treatmentrecommendations conflicting (Miller &Weijer, 2003). Aphysician medical interventions thephysician is medica expert ofthe consensus the threshold for the physician’s duty ofpe mi a reasonable wouldconsistent be with whatwouldbe recommended for themby atleast of randomization asaresult receive would subjects that care the though even trialparticipants, topotential offered that be can options mining the dition D. If there is no additional information that leads uncertain about the best course of treatment for for of treatment course best the about uncertain C mend that duty asher views she what with dance thisparticul for recommendation treatment her in isadamant each is true; opposite Quite the views. ofher uncertain and C advising patients arbitrarily treats the opinionof the patients arbitrarilytreats of choices the on itplaces that restriction the paternalism: unjustified resents particular patient. As long as the remains that no individual clinician is uncertain about what isbest for this is in the patient’s best interestand each above described example the in as if However, community. medical larger ofthe eyes the in care” medical somehow follows directly from (a). This inference, however, is not valid; (b)above that effect the viewto ofacommon expression aclear provide Tobegin ent problems. with, Isugg tion ofthe equipoise requirement. Their view,however, differ-suffers from objection stands. requirement must exist in the mind of being treated by C by treated being designed clinical trial, ratherthanforcing 2 , andis noth , ifthere This problem cannotbe This To be clear, this is not a case where either of the clinicians involved is involved clinicians the of either where acase isnot this clear, be To Concerns about fragility fragility about Concerns 2 represent competing schools of thought about how best to treat con- i againsttaking s i participate in a clinical trial between s nority of expe 1 or C or 1 or s or ing about treatments s treatments about ing 2 ? Two Dogmas of Research Ethics 1 2 . So, 1 are consistentare with the standard of“competent or s or are a central factor in Miller and Brody’s rejec- rt clinicians. eliminated by adopti i 2 goestohislocalli at random, within the context of a well- relevant uncertainty for the equipoise the for uncertainty relevant l communitythatdetermineswhich physician believesthat one treatment may recognize that the existence of that the other is other the that a single expertas ested above that Miller and Brody that Miller ested above of personal care, she will not recom- willnot she care, personal of obligatedtoofferherpatients rsonal care according towhich it is the individual clinician then my clinician theindividual indicatesthat the larger medical ar patient. If each acts in acts accor- Ifeach ar patient. i torandomly choose between 1 1 ors ands i . If the equipoise require- equipoise the . If 2 1 in this circumstance rep- circumstance this in ors i 2 . However, toprevent that lead that brary and finds that C ng a robust epistemic 2 i sovereignindeter- because she she is not because tobelieve C not, then the fact not, thenthe i to indepen- i toallow 1 over 107 1 i Downloaded By: [London, Alex John] At: 19:33 20 April 2007 act, rule, policy,etc.,—is ofan instrument—an goodness viewthat the is the Consequentialism 1979). result ofcombiningconsequentialism andcontroversialTh morally problematic. areboth claims that offurther (a) with from addition the follows (b) only 108 framework. previous paragraphin order toknow how to apply their proposed the in outlined issues the of account a reasoned need therefore We 2006). (London, met been has criterion this when about judgments reasoned pluralistic,membershelpingliberal ofa democratic community toarriveat for rule decision useful interpersonally some weneed then social value, But if losses toindividual welfare really be quantified. cannot and claim, they of“judgment,” matters to down boil desires for a kind of precision that cannot be had: suchissues ultimately deliberators. participants areleft of individualtrial and value ofscientificinformation the unavoidable on their view. Butthe variety ofdifferent waysof specifying (b) aboveandthetwosupportingargument of acceptance Their utility. insocial gains for ofindividuals interests health What value the trade-off or weigh how to 3. cases, and in concrete defined, value, so that measure how to 2. how to represent or quantify the value ofthe information that a trial 1. ut against gains insocial welfare individual in tradeoffs evaluate to deliberators requires framework proposed has been widely criticized on moral grounds. that good common simplistic viewofthe overly isan however, view, latter utilityofth maximize thesummed therefore, advancingthe common good hasto beunderstood astrying to the sumof the individual utilities in the other. For(b) tofollow from(a), another justin case the sum of the indi one therefore, utilitarian, the For state. (u welfare of the total summed the by als. Sum-ranking is the view thatthe goodness of an outcome is determined states sufficientto indicatehow not is this alone consequentialism, if(a)implies Even about. itbrings that estsofindividual trialparticipants (London &Kadane,2003). generate might Miller and Brody have triedto dismiss theseworries asmisguided Whether or not we accept these addi isWelfarismthe viewin consistsgoodness the that welfare ofindividu- is clear in their frameworkisthepermissibilityclear in oftradingoffthe determinedby the goodness Alex John London ofaffairs should be evaluated. ility. However, they do not define e individual community members. The as vasttheimaginations ofdifferent with welfarism and sum-ranking (Sen,with welfarismandsum-ranking of that informatio that of of tradingitoffagainstthe interests state of affairs isatleastasgood vidual utilities is tility) information contained in the are justified by offsetting gains in is is becauseis utilitarianismthe is tional claims,Mi s infavorof (d)makethisclaim ofthe stateofaffairs n againsttheinter- at least as large as large at leastas ller and Brody’s Downloaded By: [London, Alex John] At: 19:33 20 April 2007 developing and exercising one’s capacities of principlesright(Rawls, 1982). Such basic or generic interestsinclude conception ofthe goodto regulate and toformulate moral powers:thecapacity that are constitutive of what the philos being able to cultivate andto exerci what Iwill call“basicinterests.” These bers of such acommunity can recognize each as sharinga common set of social decision making and public policy. Fortunately, theindividual mem- personal interests and these differences are a common source of conflict in nuts. little asa group former the in viewindividuals even may and stimulation tual mountain climbing or sky diving, others may incline more toward intellec- personal intense value individuals some andplans projectsthatthey adopt inpursuitthis. ofexample, For while life particular the and good the of conception individual their of light in interests.” “personal that individual’s agent ofan good individual the view, On this 2003). (London, good the common and individual the between extensive benefits fo benefits extensive part research topresent harms potential claimthat explicit and correlative the and members, community welfare of shouldserve the commongood, unders conflict. most,caseswhereintuitions is needed exactly thosecaseswhereit to deliberatorsin guidance reasoned ameansofproviding without researchethics will leave seem to subjects it.”This,however, “worth risks whetherthe decide to order intuitions in use their to deliberators andinsteadexhort research clinical of order toguidetheirevaluations individual viding decision makers with ethics the research community should drop thepretense that it is pro- research is aninherently research farism andsum-ranking,therefore research ethics (London, 2006). Although it accepts (a) above, it rejects wel- What I call the integrat In liberal democraticcommunities individuals maydiffer radically intheir distinction different avery draws approach integrative the Instead, As a result, itrejectsth As a On the other hand, if such tradeoffs really cannot be specified,then cannot be ifsuchtradeoffsreally hand, On theother IV. THEINTEGRATIVEAPPROACH r future patients. ive approach rejectsboth of the above dogmas of utilitarian enterprise. Two Dogmas of Research Ethics e underlying ideaclinical that research seeks to se those fundamental human capacities These are the interests that agents have agents that interests the are These are intereststhateachindividual has in opher John Rawls refers to JohnRawls refers as to our two opher our conductourbasisthe withotherson is identifiedwithwhatIrefertoas challengethrough activities suchas and topursue alife plan based on a rejects the claim in the rejects astandardin thattheycanapply icipants are justified by sufficiently by justified are icipants for reflective thought andpractical tood implicitly as theaggregated tood implicitly (b)thatclinical 109 Downloaded By: [London, Alex John] At: 19:33 20 April 2007 enterprise ofclinical research iscarri nity members. The integrative approach, therefore, seeks to ensure thatthe and interventionsthatar among community members for the purpose of producing the information labor dividing of way one represents research Clinical others. of assistance th others, activitiesof oppressive the by sickness and disease, social deprivation or environmental hazard, or by community. agency and havethe opportunity tocultivate and exercisetheir basiccapacities for willingintere totakeon,asapersonal are who individuals with functions or duties specific matching by achieved ing definitioning ofreasonable risk: above definedof space equality. Thisis commitment reflected the in follow- the within understood members ofallcommunity equality moral mental in the pursuit in thepursuit of particularprojects tional capacities andthose havingto exercise capacities theeffectivefreedom decision making,developing and cult 110 and to engage in meaningful relationships with others (London, 2003). (London, others with relationships in engage meaningful and to possible forthemto formulate and to exercise thosebasic intellectual, affect ethics. Instead of appealing to the role tothe appealing of Instead ethics. interests of each of the relevant part interests ofeachtherelevant of one or more parties, are maximally responsive to the underlying basic require thoughtheymay solutions that, though the of creation advance the common good ofeach labor is to create and to maintain basi and advance. One of the central moral th interests members whose social division oflabor thatmustjustifiable be totheindividual community ideal. In this view,clinical researchis participants, it lo to subjectresearch researchers to define the parameters on the risksto which it is permissible higher-order interest, common to allinterest, commonto higher-order It good. their individual after ing and pursuing their personal interests, and therefore as responsible forlook- Ittreats equal treatment. claim to just a have members all community which over domain the equality,” of “space On thisview,whenthe basicinterests restricted,are ofsome whether The integrativeappr The integrative approach alsoreje pants arereasonable Definition ofReasonable Risk: integrative solutions just in case they case in just e necessary to provide su e necessarytoprovide oach uses this set of basic interests to define the at division of labor is supposed to safeguard to supposed is labor of at division Alex John London and meaningful social relationships. Riskstoindividua identifies the common good with the goodwith the common identifies ed out in a way that respects the funda- the respects inawaythat out ed ey can make a legitimateclaimonthe viewed asone element within a larger individuals as resp individuals community members, ies. In general,su ies. oks insteadtoanegalitarian political ivating one’s affective basic or emo- st, the project of ensuring that others that ensuring of project the st, ive, andsocialabil pursue particular pursue particular community member.Thisisdone c social institutions that foster and thatfoster c social institutions -related obligation cts the second dogmaof cts thesecond research alterations in the personal interests the personal in alterations missions of the social division of division social the of missions to social problems. These tosocialproblems. are ch assistance tocommu- ch assistance l researchpartici- ch solutionscanbe onsible forshaping onsible goals and projects ities that makeit that ities s ofclinicians or in beingable to Downloaded By: [London, Alex John] At: 19:33 20 April 2007 two criteria for equal equal regard: for two criteria being free to shape and to pursue als prevent those individuals fromsharing equally in the common good of special consideration because restrictionsonbasic the interests ofindividu- diseases that threatenor participants themselv in which research below. criteria two operational the by explicated be will claim last This members. community other of interests basic the for shown is that concern of degree same the with inconsistent pation must not riskstothebasi pose partici- such that is however, constraint, The difficult. otherwise or painful, permissibleis alsoask them to toendure experiences that areunpleasant, energythat might otherwise havebeen directed to other projects orgoals. It in aresearchinitiativethatmi ipation individuals whether they arewilling to ta the secure sacrifice some of their to toalter, even risk, or members to community ask permissible individual itis that claim normative the reflects distinction This participants. of interests the conduct ofsound science. The second partquantifies overbasic the as reasonable,risks count ticipants, both basicand personal, and represents the idea thatin order to issues areparticularly salie equal regard for thebasic by consideringwhat conditions have to decisions. tomakethese informed informed consent to ensure thatparticipants are sufficiently free and fallstoadditional It sonal interests. a trialthatmeets this standardareacce pants arethen free to decide for themselves whether the risksthatremain in to permissible is it risk that of level The Integrative Approach, therefore, adopts the followingofthe first as This focusonbasicinterestsrepres This ofthisdefinitionquanti part first The Operational criteria for theapplicati Operational criteria 2. into of intrusion least amount the require 1. research participants andnon-particip research Criterion: First Operational research is intended toserve. is intended research that interests whose largercommunity ofthe themembers pants and fo regard an equal are consistentwith necessary in order to facilitate orderto in necessary basic interests basic personal interests personal of others. This meansThis that ofothers. Two Dogmas of Research Ethics restrict interests. restrict basic their situation This requires interests of participants interests ofparticipants nt inthisregard.Thefirs must be reduced to those that are necessary for necessary that are those to reduced be must Equal regard the basicinterestsof regard for Equal a reasonableindivi sound scientific inquiry and scientificinquiry sound offer requirements relating toequityand requirementsrelating ght involve the dedicationof timeand ptable in light of theirparticular per- es suffer from sicknesses, injuries, or fromsicknesses,injuries, es suffer be met for clinical research to show met forclinical researchto be ants requires that when the basic when the ants requiresthat to prospective pa c interests ofparticipantsthat are aspartof an effort to advance or ke up,asa personal project,partic- on of thisdefinition aregenerated fies over all ofthe interests of par- ents a socialju r the basicinterestspartici-r the ofstudy the interests of participantsthatis interests the and non-participants. Two t relates to the situation relates tothe t it to is permissible ask dual lifeplan. dgment about the about dgment rticipants. Partici- rticipants. 111 Downloaded By: [London, Alex John] At: 19:33 20 April 2007 prospective trial participant individually. is a set of available treatment options options ofavailabletreatment aset is there which for condition medical a particular with individuals of set the be particular clinical trial satisfie restricted by sickness, by restricted inte whosebasic of those interests determining what isrequired in order of normativity the for a source as not This operational criterio 112 restricted by sickness, by restricted basic the when mission this fills members andabouttheroleofclinical tion asto andtoadvanc so preserve tion, butin broader claims about the need forbasic social structures to func- indivi the in not grounded, requirement here too thereimportant aresome diffe recommended forthembyatleastareas of receiving assured is trial clinical pants. Whenthis conditionismet, ea restricted is scope thatits is difference salient most The 1996). (Kadane, colleagues and Kadane by recommended Thisimportant conditionissimilar in re ventions from S to which individual individual which Sto from ventions clinical trial and let let and trial clinical treatment options treatment flict or uncertainty about the relativeuncertainty ther about flict or populations whereas the above practica The following practical testis then used to determine whether or not a Second, theequipoiseis requirement This practical testisalsosimilar to between, expert clinicians about whether aboutwhether expertclinicians between, vidual vention in vention within ofcompetent the threshold medi care andprotectionafforded to that of members interests of an individual particip interests ofanindividual Practical Test for First Criterion: Test forFirst Practical of competent medicalcare. protected inaway and advanced that sickness,injury ordisease, the basic i just in case there is either uncertainty among, orconflict among, either uncertainty case thereis justin U i S is a member of member isa as a treatment for individual forindividual treatment a as for the individual U i * be the set of interventions from injury, ordisease. injury, injury, ordisease. injury, n invokes the threshold of competent medical care, s this operational criterion. Let Let criterion. operational s this Alex John London U i *. a package ofmedical carethatwouldbea package ant are threatened ant are i interests ofcommunitymembersare i . A treatment treatment A might be allocated might bewithin aparticular e the basic interests ofall community e thebasic interests S to the basic interests ofstudypartici- basic interests tothe this framework,butasastandardfor rests are themselves threatened or threatened themselves are rests = { interests of that individual must ofthat be interests individual apeutic meritsinterventions ofaset of onable minority of The reason forthis is ch individual whoparticipatesina does not fall below the threshold the fall below not does spects to the criteria of admissibility of criteria the to spects to show equal regard for the basic showequalregardforthe to rences. First, the moral force of this the moralforce First, rences. medicine asasocial structurethat individual’s basic interests falls basic interests individual’s Freedman’s clinical equipoise, but clinicalequipoise, Freedman’s dual physician’s therapeutic obliga- l test istobe applied toeach cal care just incase eachinter- s sometimes applied to entire trial sometimes appliedto 1 i s …, . For each individual in For each individual . j is dominated by other by any isdominated s m }. Let s j is admissible for indi- for is admissible or compromised by or compromised U S i that areadmissible be the set of inter- expert clinicians. simply that con- simply that I = {1,… I , the i ,… n } Downloaded By: [London, Alex John] At: 19:33 20 April 2007 cians) recommends interventions Those recommendations are medical condition.of competingto managinghis representatives approaches example, In that a particularpatien value conflict that Idescribed above (London, 2007; Evans& London, 2006). an treat failed tosee how the clinical lar clinical characteristic notandsome individuals forothers,depending may existfor their particu- on clinical trial emerge,forexample,in clinical trial size from afixed As data requirement. theequipoise frameworks thatendorse ommends s conflict remains and the trial may continue (London, 2007). (London, continue thetrialmay conflict remainsand then recommendation, are, continue to makeacompetingtreatment or would longer arenot clinicians Ifsome flict. con- clinical eliminate to evidence sufficient it hasgenerated if only terminated be trialto the requires standard above the cases. However, to continueinsuch i mind ofthe the uncertainty in require that Views theothers. treatmentover for one preference mayforma tain (London, 2006). (London, centralto the integrative approachmi only be able togestureat how therequirement toshow equal regardthatis fundamental open problem in research ethics. In the space remaining I will on solely for thepurposesoffacilitatin ispermi it ofsubjects basic interests of risk thei to their personal interests but which neverthelesssome pose additional degree impact directly most often that procedures to research themselves expose ests ofintrusion, research they neverthelesspose some als,that in they involve discomfortor some degree ofbodily orpersonal participants.such procedures affect mostimmediately the personal interests of individu- trea sought simply they if exposed be Thepants to undergo tests or diagnostic sameinterventions to which they would not isthe conduct ofsound clinical research true for thing, one For risks. associated the of reasonableness the establishing for healthy sufficient not are alone conditions these However, alike. non-participants subjects for th consistent withanequalregard whoor diseaseness participate inresearchthey receive alevelofthat is care when individuals whose basic interests are threatened orrestricted by sick- resolutionthe ofclinical conflictwh The above test also avoids the criticism of fragility that is often leveled at leveled often is offragilitythat the criticism alsoavoids test above The The first operational criterionandits It remains to establish, therefore, wh individual patient 2 over s r basicinterests. 1 forthesameindividual. s. Onereason that equipoise theorists havelargely isthattheyfail to takeseriously the phenomenon of Two Dogmas of Research Ethics in conflictbecause one ph community 1 over s over t received treatment recommendations from dividual clinicians clinicians dividual uncertain, but other reasonable clinicians otherreasonable uncertain, but ssible to ask potential subjects to take to potentialsubjects ask to ssible tment in a clinicaltment in when setting. Even ile, at the same time, ensuringthat ndividual clinician cannotpermittrials clinician ndividual sometimes requires research partici- research requires sometimes g scientific inquiry. This constitutes a constitutes This inquiry. g scientific e basic interests of participants and ofparticipants interests e basic incremental risk tothebasicinter- risk incremental 2 ght be extended into this context this extended into be ght forindividual could be uncertain about how to how could beuncertainabout at kind of incremental risks tothe risks at kindofincremental associated practical testfacilitate practical associated ysician (orset of physi- who wereonceuncer- i whiletheother rec- 113 Downloaded By: [London, Alex John] At: 19:33 20 April 2007 114 related activities related activities in tions arepoorly enforced or are widely recognized to be inadequate. using as comparatorsactivi socially acceptableafterdu seen, atleast public oversight so that the risk-profile associated with the activity can be same this embody should activities detract fromthevalue ofclinicalre whos evils necessary are risks these do research clinical with as rock such climbing some activities, of similarity structural the establishing about how this might be achieved. compared across these activities. Iconclude with some brief suggestions being are that risks the individuate to finely how about consideration and a an of identification the requires turn, in This, criterion. operational second this for tests practical construct with t individuals associated interests of do research-related activities not purely in basic the to risks theincremental that socialthat activitiesstructurally are sim This simply cannotbeachieved. a standard fromvoluntarily prohibited assuming some indivi equality of Respect forthemoral interests in the hands of identifiable pa features ofanactivity. interests when they perceive themselves as having control over salient individuals are born primarily for the benefit of others. incr which in structure asimilar have should activities comparator appropriate therefore, possible, Where others. Consider the following operational criterion for equal regard: for equal criterion followingoperational the Consider Third, participants beartherisks Second, appropriatecompar Four featuresresearch ofthe enterprise areparticularly salient for To refine the operational content of this requirement, it is necessary to Finally,willinoften individuals are tal risks to the basicinterests of Criterion: Second Operational activities thataresimilarinstru in thec uals thatarepermitted riskstothebasicinterestsofindivid- the than notbegreater must vidual offset bythepr notareactivities that prima facie ordertofacilitate an activity In clinical research, however, participants put their put participants however, research, clinical In not add to the social value of the activity. Rather, , asrepresenting alevel ofriskthatisdeemed ties where oversight mechanisms or safety regula- e reflection. In particular, it is imperative toavoid Alex John London ator activities should bethe subject ofactive cture to the research enterprise. cture totheresearch ppropriate comparison Inallcases,the search. As such, appropriate comparator appropriate such, As search. attitude toward the associated risks. towardtheassociated attitude ilar to theilar to researchenterprise andtoensure individuals that de that individuals hose structurally similarsocialactivities. hose structurally ontext of other sociallysanctioned of other ontext exceed the incremental riskstothe basic exceed theincremental duals cannot require that individualsbe require duals cannot rties who possess a particular expertise aparticular rties who possess emental risks to the basic interests of thebasicinterests emental risksto or racecar driving, the risks associated the risks driving, racecar or ospect of direct benefit indi- ospect to the direct of benefit another social activity. First, unlike e complete elimination would not elimination would e complete terests ofparticipants associatedwith risk totheirbasic interests, since such g to accept greater risks totheir risks toacceptgreater g proposal therefore seeks to identify seeks proposaltherefore associated with associated thatwillprimarilybenefit cumulative incremen- rive from research from rive class ofactivities purely research- purely Downloaded By: [London, Alex John] At: 19:33 20 April 2007 ther. Italsosketches an approach ing clinical conflict. This alone make of participants andhighlightstherole test that is similar toclinical equipois advantage ofproviding acompelling normative foundation for apractical detailsthehaveIapproachhere. oftheThis has sketched framework that convey the importanceoftakingthese challenges up earnest.in above arguments the Hopefully, tractable. operationally more make them trie ethics that research ous activities that in research activitiesthathave a riskprof clinical in permit to appropriate be not may it activities these in relationship principal-agent no is there because However, enterprise. research to the ties cons oversight public of degrees varying tion toservingthepublicinterest, men and paramedics. The volunteer nature of these activities, their orienta- to volunteer is activities ties thatalsoinvolve a pr Brody, H. & Miller, F. G. (2003). ‘The F.G.(2003). H. & Miller, Brody, basic interestsof community the to risks to compared be should procedures research-related purely from result, the risks tothebasic interests the to safeguard and protect parties to where this createslimited but important Emanuel, E. J., Wendler, D., & Grady, C. (2000). ‘What makes clinical research ethi- research makesclinical ‘What C.(2000). &Grady, D., Wendler, J., E. Emanuel, inte ‘The (1998). G. F. &Miller, H. Brody, Foundation. My work onthis article was supported byaNewDirections Fellowship from the Andrew W. Mellon Chard, J. A. & Lilford, R. J. (1998). ‘T J. (1998). & Lilford,R. A. Chard, J. Donagan,(1977). A. ‘Informed consentin therapy andexperimentation,’ ageable tension,’ ageable tension,’ cal?’ application to managed care,’ Medicine and Philosophy Medicine and Medicine Science and Obviously, considerable workremainsbe to done flesh tothe out Perhaps the most promising place to Journal of theAmerican Medical Association, 283 dividualsin these role Kennedy Institute of , s to frame the salient issues in a way that would awaythat in issues salient the s to frame inciple-agent relationship. public service professions, public service Two Dogmas of Research Ethics 47 ACKNOWLEDGMENT , (7), 981–998. (7), 2 members that are associat membersthat , 318–329. , REFERENCES Journal ofMedicine and Philosophy, 23 he use of equipoise in he useofequipoise clinician-investigator: Unavoidable butman- Unavoidable clinician-investigator: to what remains an open problem in problem anopen remains to what and the fact that they are subject to theyaresubject that and thefact e, but whiche, applies toindividual trial rnal moralityrnal ofmedi s this framework worth pursuing fur- pursuing worth framework s this clinical researchas Ethics Journal Ethics of research participants that emanate of researchparticipants ile that is similar to the most ile thatissimilartothemost danger- interests ofthoseparticipants. Asa responsibilitieson thepartofthose titute important structural similari- structural important titute s sometimes undertake. s sometimes look forappropriatecomparator , such as volunteerfire- suchas 13 (20), 2701–2711. (20), (4), 329–346. (4), ed withsocial activi- clinical trials,’ clinical ameansofresolv- cine: Explication and cine: Explication , 384–410. Journal of Social 115 Downloaded By: [London, Alex John] At: 19:33 20 April 2007 Weijer, C. & Miller, P. B. (2004). ‘When are research risks reasonable in relation to relation in risks reasonable research are ‘When (2004). B. P. & Miller, C. Weijer, andwelfarism,’ Sen, A.(1979).‘Utilitarianism Freedman, B. (1990). ‘Placebo controlled tr controlled ‘Placebo B. (1990). Freedman, Miller, F. G.&Brody,‘A H.(2003).critique An ethicalanalysis,’ surgery: ‘Sham F. (2003). Miller, G. Marquis, D.(1983).‘Leaving therapy tochance,’ andth ‘Equipoise B.(1987). Freedman, Evans, E. L. A.J.(2006). & London, 116 Rawls, J. (1982).‘Socialunityandtheprimar Mantel,N., S. V., R., Howard, E.,Cox,D. Armitage, P.,Breslow,N. Pike, M.C., Peto, R., equipoise,’ ‘Rehabilitating C.(2003). &Weijer B. P. Miller, ‘Clinical H. (2007). Brody, Miller, F.G.& D. risks,’in reasonable and surgery ‘Sham (2006). J.B. & Kadane, J. A. London, London, A. J. (2007). ‘Clinical equipoise: Foundational requirement or fundamental or requirement Foundational ‘Clinicalequipoise: (2007). A. J. London, belief, ‘Evidence, D. (2002). Hellman, London, A. J., & Kadane J.B. (2003). ‘Sham surgery and genuine standards ofcare: standards andgenuine surgery ‘Sham (2003). &KadaneJ.B. A.J., London, ‘Theconflict F. (1986). between Gifford, C. (1974). Fried, London, A. J. (2003). ‘Threats A.J.(2003). to th London, J.B.(Ed.). Kadane, (1996). reflecti ‘Philosophical (1969). H. Jonas, London, A. J. (2006). ‘Reasonable risk in risk A. (2006). ‘Reasonable London, J. anticipated benefits?’ ception in the ethics of clinical trials,’ trials,’ clinical of ethics the in ception ics, 3 &Littlefield. York: Rowman New 211–228). (pp. England Journal of Medicine, 317 action,’ Utilitarianism Beyond and and design,’ observ prolonged requiring trials clinical McPherson, K., Peto, J., Smith P. G. (1 ics Journal, 13 Ethics,’ Benatar (Ed.), error?’ InB. Steinbock (Ed.), th in ethicaltension the resolve Can the two be reconciled?’ Can the twobereconciled?’ 571–596. Press, Oxford University obligation,’ peutic Publishing. Amsterdam: North-Holland IRB: A Review of Human Research,12 Subjects for theintegrative approach,’ Inc. Sons, & Wiley John York: New 98 Daedalus, Medicine, and Ethics, 30 human subjects research,’ research,’ subjects human (4), 41–48. Journal ofMedicineand 32 Philosophy, Journal of Law, Medicine, Ethics Medicine, of and Law, Journal British Journal ofCancer, 34 (2), 219–247. Medical Experimentation: Person (2), 93–118. (2), Cutting to theCore:Exploring th Journal of Medicine andPhilosophy,11 Nature Medicine,10 Bayesian Methods Bayesian and Ethics in aClinicalTrial Design , 375–380. (pp. 159–185). New York: Cambridge UniversityPress. (pp.159–185).NewYork:Cambridge The Report The Hastings Center The American Journal of Bioethics, 3 Alex John London Statistics inMedicine The Oxford Handbook of The OxfordHandbook Bioethics e common good: weaponsand good: Biochemical e common e randomized clinical trial,’ trial,’ clinical randomized e , 141–145. , ons on experimenting with human subjects,’ withhuman experimenting ons on ‘Equipoise and the crit the and ‘Equipoise Equipoise andtheIncoherenceofResearch clinical research: A critique and a proposal a and Acritique research: clinical and action: The failure of equipoise to and action:Thefailureofequipoise The HastingsCenterReport,33 of clinical equipoise: Therapeutic miscon- e ethics of clinical research,’ research,’ ethicsofclinical e 976). ‘Design and analysis ofrandomized and ‘Design 976). randomized clinical trials and the thera- the trialsand clinical randomized The Journal of Philosophy, 76 y goods,’ in A.Sen (Eds.), &B.Williams ials and the ials andthe logic of clinicalpurpose,’ ation of each patient. I.Introduction ofeachpatient. ation , 585–612. , (6), 570–573. (6), Hastings CenterReport,13 . Inpress. , 151–165. (6), 1–6. al Integrityand Social Policy e EthicsofCont , American Journal of Bioeth- American Journalof 25 , Kennedy Institute of Eth- of Institute Kennedy 33 (17), 2869–2885. (17), (5), 17–25. (5), (4), 347–366. eria forreasonable Journal of Law, of Journal ested Surgeries ested (4), 61–64. (4), . NewYork: (9), 463–489. (3), 19–28. (4), 40–47. The New . .