*
The principle of post-trial access in the 2008 revision of the Declaration of Helsinki

[Working paper]

Please do not quote from this manuscript without getting in touch with the author. A
developed version might be ready.
ignaciomastro@yahoo.com.ar

Ignacio Mastroleo

Abstract

The objective of this study is to critically analyze the new formulation of the principle
of post-trial access in the most recent (2008) revision of the Helsinki Declaration. The
relevant articles of the declaration are identified and two possible interpretations of the
principle of post-trial access are set out; one robust and one permissive, the latter inspired
by a procedural, and the former by a substantive principle of distributive justice. In
conclusion, a critical evaluation of both interpretations is presented and arguments in
favor of the robust one advanced.

The principle of post-trial access and its relation with the principle of responsiveness

In the sixth revision of the Declaration of Helsinki, carried out in 2008, the principle
of post-trial access is set out in paragraph 33, which replaced paragraph 30 of the
previous version of the declaration.
Paragraph 33. At the conclusion of the study, patients entered into the study are entitled [1] to be
informed about the outcome of the study and [2] to share any benefits that result from it, for
example, access [2.1] to interventions identified as beneficial in the study or [2.2] to other
appropriate care or [2.3] benefits.

To this must be added the final sentence of paragraph 14 of the 2008 text, which
establishes the information the protocol must contain with regard to the way the principle
of post-trial access must be addressed.
Paragraph 14. […]The protocol should describe arrangements for post-study access by study
subjects to interventions identified as beneficial in the study or access to other appropriate care or
benefits.

                                                            
*
This study was carried out with the aid of a grant awarded by CONICET in the framework of project
UBACyT F093 “An analysis of the concepts of vulnerability and exploitation in bioethics and their impact
on research ethics and other areas of applied ethics”, directed by Dr. Florencia Luna and Dr. Marcelo
Alegre.
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Furthermore, paragraphs 14 and 33 should not be read without reference to paragraph

17 of the Declaration, especially in so far as it is relevant to developing countries.
Paragraph 17.  Medical research involving a disadvantaged or vulnerable population or
community is only justified if the research is responsive to the health needs and priorities of this
population or community and if there is a reasonable likelihood that this population or community
stands to benefit from the results of the research.

This paragraph, which replaces paragraph 19 of the previous version of the

Declaration, sets out the principle of responsiveness.1 This principle restricts the number
of studies which may be carried out in vulnerable or disadvantaged populations on the
basis of two conditions (1), the importance of the study (understood in terms of a
response to its needs and health priorities) and (2), the reasonable possibility of access to
the benefits of the study for the host community.2 Thus, the demand that studies be
responsive sets a moral limit to efficient clinical research by ruling out “certain physically
possible options”.3 However, as London4 indicates, the responsiveness of a study may be
interpreted in different ways and it is therefore necessary to consider two of them, one
robust and the other more permissive.
(1) A robust interpretation of the principle of responsiveness. This interpretation
holds that a study is responsive if it responds to those needs which are also health
priorities of the population or community in question. In London’s view, “[…] it is not
sufficient to establish that the health need in question is merely represented in the host
community. Rather, the health need in question must be sufficiently urgent or important

                                                            
1
The most fully developed statement of the responsiveness requirement may be found in CIOMS.
International Ethical Guidelines for Biomedical Research Involving Human Subjects; 2002,
http://www.cioms.ch/frame_guidelines_nov_2002.htm. Guideline 3 of the 2002 text “Ethical review of
externally sponsored research” states that “The health authorities of the host country, as well as a national
or local ethical review committee, should ensure that the proposed research is responsive to the health
needs and priorities of the host country and meets the requisite ethical standards”. While, guideline 10
“Research in populations and communities with limited resources” states that “Before undertaking research
in a population or community with limited resources, the sponsor and the investigator must make every
effort to ensure that: (i) the research is responsive to the health needs and the priorities of the population or
community in which it is to be carried out; and (ii) any intervention or product developed, or knowledge
generated, will be made reasonably available for the benefit of that population or community”.
2
In order to simplify the interpretative model it is assumed that the second condition of the principle of
responsiveness is complied with. For an analysis of the problem of post-trial access by the community see
Mastroleo I. Justicia global e investigación biomédica: la obligación post investigación hacia la comunidad
anfitriona. Perspectivas Bioéticas 2007; 12(23):76-92.
3
Kitcher P. Science, truth and democracy. Oxford: Oxford University Press; 1997, p. 118.
4
London A. Responsiveness to host community health needs. In: Emanuel JE, Grady C, Crouch R, Lie R,
L, Miller F, Wendler D, editors. The Oxford Textbook of Clinical Research Ethics. New York: Oxford
University Press; 2008, 737-44, http://www.hss.cmu.edu/philosophy/london/London--
ResponsivenessOUP.pdf. London refers to the responsiveness requirement as it is set out in the framework
of CIOMS 2002. His analysis is equally valid for the 2008 Helsinki Declaration.
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that finding the means of addressing it represents a judicious use of the community’s
scarce social resources”.5 What constitutes a health priority is decided by communities
themselves and this decision guides the organization of research in the country.6
(2) A permissive interpretation of the responsiveness principle. This interpretation
is based on a literal reading of paragraph 17. London states that “[…] because ‘the health
needs’ of the host community do not necessarily fall under the scope of ‘the priorities’ of
that community […], a literal reading of this guideline is consistent with the more liberal
view”.7 Defenders of this view state that research is permissible if it targets a health need
that is simply present in the community, although it may not be the most pressing or
important, and if it is “[…] responsive to other priorities of the host community –such as
strengthening the health-care infrastructure, training and educating medical personnel,
and perhaps also fostering economic activity that would result from hosting the
research”.8
These interpretations directly affect the analysis of paragraph 33 of the Declaration, a
task to which I will now turn.

An analysis of the principle of post-trial access in the 2008 Helsinki Declaration

In common with the majority of other declarations of ethical principles9, the ethical
justification of paragraph 33 of the Declaration is not explicitly stated in the text of the
Declaration itself. It will therefore be necessary to here make explicit an interpretation of
the principle of post-trial access, in order to see how it might be satisfied in practice.
One way of interpreting paragraph 33 of the Declaration is in the light of a substantive
principle of distributive justice.10 As Ballantyne states, “a substantive normative principle
                                                            
5
London, op. cit., 738.
6
“Some important steps have recently been taken in this regard by a variety of communities that have
sought to define their national health priorities so that research can focus on what has been termed essential
national health research, or ENHR. ENHR refers to a strategy of systematic priority setting within which
research questions can be identified and prioritized according to factors such as economic impact, cost
effectiveness, effects on equity, social justice, and their contribution to strengthening research capacity in
the host community” London, op. cit., 741.
7
Ibid., 739. London refers to the responsiveness requirement as it is set out in the framework of CIOMS
2002. His analysis is equally valid for the 2008 Helsinki Declaration. See also note 1.
8
Loc. cit..
9
For example UNESCO. Universal Declaration of Bioethics and Human Rights; 2005,
http://unesdoc.unesco.org/images/0014/001461/146180E.pdf.
10
Wolff J. Models of distributive justice. Empathy and Fairness; 2006, p. 165-170,
http://www.homepages.ucl.ac.uk/~uctyjow/MDJ.doc. See also Barry B. Theories of justice. Berkeley:
University of California Press; 1989.
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of fair distribution is one that prescribes a certain outcome as morally superior to other
outcomes in a given context”.11 In turn, substantive principles of justice can be
distinguished from a procedural account of fairness which “[…] is non-prescriptive with
regards to the final distribution of benefit and cannot predict in advance what the morally
appropriate outcome will be”.12
A possible candidate for a substantive account of fairness is the principle of justice as
reciprocity or equitable exchange. This view of justice is closely related to the ideas of
proportionality and that which is deserved; those that make a contribution to society or a
social enterprise deserve to be recompensed in proportion to their contribution. As the
National Bioethics Advisory Commission (NBAC) puts it, “Justice as reciprocity […] is
concerned with what people deserve as a function of what they have contributed to an
enterprise or to society”.13 In this way the particular contribution of each individual –in
terms of possible risks run as well as time given to the study– gives each the right to post-
trial access to any intervention shown to be beneficial. Apart from the principle of justice
as reciprocity, there are other substantive principles of justice which may be applied to
the interpretation of paragraph 33 –one of them being the principle of justice as
impartiality14– and it is entirely possible that some may function better in this role than
others. For example, under the principle of justice as reciprocity, it might be held that
trial participants have a special right of access to interventions identified as beneficial, a
right not applicable to other members of the community. Such a view might clash with
those arising from other substantive principles of justice. In any case, it is not my
intention here to determine the most appropriate principles of justice but rather to apply
one of those commonly used in clinical research ethics, to illustrate the robust
interpretation.15

                                                            
11
Ballantyne A. Fair benefits’ accounts of exploitation require a normative principle of fairness: response
to Gbadegesin and Wendler, and Emmanuel et al. Bioethics 2008, 22(4):239-44(241).
12
Loc. cit..
13
NBAC. Ethical and policy issues in international research: clinical trials in developing countries; 2001,
vol. 1, p. 59, en http://bioethics.georgetown.edu/nbac/clinical/Vol1.pdf.
14
London’s human development model appears to be based on a notion of distributive justice of this type,
see London A. Justice and the human development approach to international research. Hastings Center
Report 2005, 35(1):24-37
15
NBAC, op. cit., makes use of a notion of justice as reciprocity as a basis for the justification of post-trial
obligation to provide participants with beneficial interventions identified in the trial. However, it arrives at
more modest conclusions than those of this study.
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The practical implications of the robust interpretation of “access to interventions

identified by the study as beneficial” can be better understood with the aid of the
following example.
Natalia Garcia is Argentine and decides to participate in a clinical trial of an
experimental treatment for a chronic illness from which she suffers. Two months after
starting to take the new treatment the first signs of its effectiveness begin to appear in the
form of a fall in the count of a specific indicator of the condition. Natalia starts to feel
better and the indicators for her condition fall at each measurement carried out in the
trial. The trial ends at the planned time and its sponsors seeks approval from the
regulatory agency for the product to be licensed for the treatment of the condition
mentioned in the protocol. Everything indicates that Natalia would continue to benefit
from the experimental treatment and she has no way of obtaining it on her own account.16
Is Natalia entitled to continue receiving the experimental treatment after the study
ends? Under the robust interpretation, this case leaves no room for doubt; Natalia has the
right to continue receiving the treatment identified as beneficial. This position does not
concern itself with the question of on whom should fall the responsibility of paying for
the treatment and over what period of time it should continue, bearing in mind that the
condition concerned is chronic.17 Nevertheless, the robust interpretation does establish
what a fair outcome would be, regardless of what had been agreed by the parties in their
negotiations prior to the trial and serves as a moral standard for the assessment of the
outcome of the bargaining process.
In the same way, “access to appropriate attention” may be exemplified by the case of
trials of HIV vaccines or microbicides.18 Here access to treatment with antiretrovirals for
those participants who turn out to be HIV positive during the study would be a good
example of “other appropriate attention” which would be justified by the right to post-
trial access as set out in the 2008 Declaration.
Finally, “access to other appropriate benefits” would refer to indirect or ancillary
benefits arising from the carrying out of the study. It is important to emphasize that under

                                                            
16
This example is an adaptation of found in Grady C. The challenge of assuring continued post-trial access
to beneficial treatment. Yale Journal of Health Policy Law and Ethics 2005; 5(1):425-35.
17
For some considerations in this regard see Zong Z. Should post-trial provision of beneficial experimental
interventions be mandatory in developing countries? Journal of Medical Ethics 2008; 34:188-192. See also
Grady, op. cit..
18
Schüklenk U. Bioethics in the developing world. In: Iltis A, Johnson SH, Hinze, BA, editors. Legal
perspectives in bioethics. New York: Routledge; 2008. p. 274-291.
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the robust interpretation “access to other appropriate benefits” cannot replace “access to
the intervention identified as beneficial” or “access to appropriate attention”. This means
that if Natalia needs the intervention identified as beneficial, her right of access to it
cannot be vindicated by “other appropriate benefits” such as access to better quality
healthcare or by referring to the incentive to economic activity arising from the carrying
out of the study in the community, or the training received by medical staff and ethics
committees. Similar considerations apply to “access to appropriate attention”.
The robust interpretation of the principle of post-trial access appears more reasonable
when read in the light of the robust interpretation of responsiveness to host community
health needs outlined above. Taken together, they reduce the possible options for efficient
clinical trials in favor of a set of ethically valid studies that are carried out on the health
priorities of the host community and which are designed to guarantee trial participants’
access to identified beneficial interventions and other appropriate benefits when they
need them.19
There are other approaches to the principle of post-trial access not inspired by a
substantive account of fairness. The most important of them is the fair benefits model.20
As London maintains21, it is possible to provide more restrictive interpretations of the fair
benefits model than will be set out here. Nevertheless, in its most liberal version, this
model would sustain the following two theses:
(1) The health needs of the community. Here the fair benefits model follows what
has been established by the permissive interpretation of the principle of responsiveness
(paragraph 17). It is not necessary for a community’s health necessities to also be health
priorities. It would be sufficient for certain health needs to be present in the community
or population concerned for the study to have social value and for its carrying out to have
a priori justification, as long as this needs are conjoined with community priorities not
directly related to the study.
(2) Post-trial benefits. In the model developed by Emmanuel et al. in order to
establish fair benefits and eliminate exploitation it would only be necessary for there to
be discussion and agreement between the parties; the community and the sponsor, with

                                                            
19
Zong, op. cit. tries to establish criteria for determining the cases in which intervention may be necessary.
20
The Participants in the 2001 Conference on Ethical Aspects of Research in Developing Countries [
hereafter Emanuel et al.]. Moral standards for research in developing countries: from ‘‘reasonable
availability” to “fair benefits”. Hastings Center Report 2004; 34(3):17–27.
21
London, op. cit.
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regard to “a broad range of costs and benefits”.22 Defenders of the fair benefits model
hold that “access to interventions identified as beneficial by the study” cannot be allowed
to function as a moral limit for the carrying out of a study.23 These authors count
improved research capacity and improved training of ethics committees among the
“broad range of benefits” as these indirectly benefit study participants and should
therefore, in their view, be counted as part of the fair benefits received. Therefore, from
the standpoint of the fair benefits model, even though participants in a trial may not
receive a treatment with clear health benefits for them, the study can still be regarded as
ethically valid if it has their consent and that of their community.
To illustrate the permissive interpretation of the principle of post-trial access
sustained by the fair benefit model, I will turn once again to the example of Natalia
Garcia.
Possibility A. After negotiations between the sponsors, researchers, IRB (the study’s ethics committee)
and the community, it is decided that trial participants –Natalia among them– who respond positively to
the experimental treatment will continue to have access to it after the trial concludes.

Possibility B. Despite its positive effects on her health, at the end of the trial Natalia ceases to have
access to the experimental treatment. Nevertheless, the principle of post-trial access is considered to
have been complied with as Natalia has consented to participating in the trial and a significant quantity
of “other appropriate benefits” have been provided for the community, as agreed in the pre-study
negotiations.

In spite of what our moral intuitions may tell us, for the defender of the fair benefits
model, the two possibilities are equally just, as long as they both arise from a transparent
process of negotiation between the parties –autonomous moral agents all– and the
consent of all concerned was obtained.

A critique of the permissive interpretation of the fair benefits model

At least two criticisms can be made of the fair benefits model. In the first place, as I
have shown above, Emmanuel et al. use a procedural conception of justice on the basis of

                                                            
22
Emanuel et al., op. cit., 26.
23
Emanuel et al., op. cit., hold that it is an error to demand access to interventions identified as beneficial
because not all trials produce such benefits for participants or in any case do not do so immediately, for
example in phase I and II trials. One possible response to this position would be to point out that the fact
that not all trials produce beneficial interventions tells us nothing about whether participants have a right to
them in trials which do produce them and offers no support for the idea that access to them should be
decided on the basis of negotiations between the parties. Zong, op. cit., looks at this question in more detail.
A robust interpretation of how phase I and II trials should be carried out in developing countries can be
found in London A, Kimmelman J. Justice in translation: from bench to bedside in the developing world,
The Lancet 2008, 372(9632):82-85.
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which the fair distribution of benefits is decided on a case by case basis, without
reference to any independent substantive standard and appealing solely to the real consent
of the participants in the study and their community. But, as Ballentyne states, this
amounts to a problem because “[…] in the absence of a robust normative principle of
fairness, exploitation collapses back into a debate about consent”.24 And, as defenders of
the fair benefits model themselves recognize “[...] neither the trial participants’ consent
nor the host community’s consent preclude exploitation”.25 The fair benefits model
might, therefore, permit cases of exploitation with consent that it cannot itself detect as
there is no normative principle of justice beyond the informed agreement of the parties.26
For example, one might consider that in Possibility B Natalia is being treated unjustly,
even if she has given her consent to not receiving post trial access to treatment beneficial
to her; “unjustly” here understood in terms of a substantive, independent standard of
justice. The fair benefits model cannot produce such a standard and a different principle
of distributive justice will have to be sought. An example of such a principle could be the
principle of justice as reciprocity that would hold that insofar as Natalia has accepted the
risks of participating in the trial and has collaborated with the study she is therefore
entitled to continue to receive the treatment. Or perhaps the principle of justice as need27
which would state that that if Natalia requires access to the experimental treatment after
the trial and has no other way of obtaining it then she has the right to receive the
identified beneficial intervention.
The closest that Emmanuel et al. get to accept an independent standard of justice is in
their proposal relating to transparency. In their view there ought to exist a repository –
with public access– containing a record of all previous agreements on post-trial access,
managed by an independent body such as the WHO. Again, this procedural principle does
not preclude exploitation and therefore the principle of transparency would have to be

                                                            
24
Ballantyne, op. cit., 241.
25
Loc. cit..
26
The standard interpretation of the concept of exploitation in clinical research ethics differs greatly from
Marxist and other macro level conceptions. Emanuel et al.’s permissive interpretation relies on a micro
level conception of exploitation developed by Wertheimer A. Exploitation in clinical research. In: Hawkins
JS, Emanuel EJ, editors. Exploitation and developing countries: the ethics of clinical research. Princeton:
Princeton University Press; 2008, p. 63-104. A competing, more substantive micro level conception of
exploitation is developed by Macklin R. Avoiding exploitation. Double standards in medical research in
developing countries. Cambridge: Cambridge University Press; 2004, p. 99-130.
27
Sabbagh C. The Dimension of social solidarity in distributive justice. Social Science Information 2003;
42(2):255-276.

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supplemented by a substantive principle which would be used to evaluate if agreements

reached are just or not, regardless of the question of consent.
The fact that we have to choose between more than one principle of justice with which
to evaluate clinical investigations brings me to my second criticism. In my opinion, the
permissive interpretation of Helsinki’s principle of post-trial access held by the fair
benefits model is not sensitive either to the social reality or scientific practice of many
clinical studies carried out in developing countries. Emmanuel et al.’s model is based on
an account of fairness called justice as mutual advantage. This view can be expressed in
the following way; if each moral agent acts on his own account he or she will achieve a
result for him or herself. However, if agents cooperate, they will produce a better result,
with a surplus arising from cooperation between them. Justice as mutual advantage
therefore consists of finding a mechanism for dividing this surplus and is strongly
associated with the idea of negotiation.28 On this basis a negotiation will be regarded as
just when “those with greater negotiating power receive more”.29 And, as Wolff indicates
“[...] one’s negotiating power is not determined by one’s contribution but rather by how
necessary one’s agreement is for the other parties”.30
Let us examine how the principle of justice as mutual advantage works in the case
with which we are concerned. Given the nature of clinical research, the sponsors and
researchers of a study usually require a certain number of people who meet eligibility
criteria. However, they rarely need the agreement of any particular person to carry out the
study. If what a person has to offer (in this case, his or her participation in the trial) can
also be offered by many other people, his or her negotiating power and the benefits they
receive, will be less than if this was not the case. Therefore, the participants in a clinical
trial have less negotiating power than the sponsors and researchers. This structural
asymmetry in the relationship between them is even worse in developing countries where
background circumstances of injustice restrict community members’ possibilities of
obtaining a reasonable standard of healthcare outside clinical research.31

                                                            
28
Wolff, op. cit.
29
Ibid.
30
Ibid.
31
London, 2008, op. cit., 743 arrives at similar conclusions “[…] the ancillary or indirect benefits that can
be generated from research are unlikely to address root causes of disease in the developing world in a
sustainable way. In particular, the disparities in bargaining power between research sponsors and host
communities, combined with constant pressures to limit the costs associated with individual research
projects, make it likely that there will remain a fairly low ceiling on the kind and extent of indirect benefits
that host communities can access through the bargaining process”.
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This does not mean that the principle of justice as mutual advantage cannot be applied
in any circumstances. As Sabbagh32 states, there are attributes of social context that have
been found relevant for the endorsement of principles of justice. Among them, I would
like to highlight are the following three: (i) goals, (ii) relations between agents and (iii)
exchanged resource. According to Sabbagh, the principle of justice as mutual advantage
(called by the author the principle of equity) is usually endorsed in socio-economical
contexts where, (i) the desired goal is to improve “efficiency and productivity”33; (ii) the
relationship between the moral agents is one of competition and their degree of
interdependence is low (Sabbagh34 mentions employer-employee relations and bargaining
interactions as being typical of relationships of this sort) and (iii) the benefits to be
distributed have a certain universal character (for example, money and information).
Nevertheless, the attributes of the social contexts in which clinical research is usually
carried out do not commonly coincide with those necessary to endorse the application of
the principle of justice as mutual advantage for the following reasons. Firstly, even
though the majority of clinical trials form part of a process of industrial production that
must be carried out as efficiently as possible, to the degree that they require international
cooperation the objective of the principle of justice applied should be furthering “welfare
to all participants”35 and inducing “favorable terms of co-operation, mutual support and
evaluation”.36 Secondly, although researchers and trial participants may have competing
interests, their relations are of cooperation and of moderate interdependence.
Furthermore, many participants in clinical trials are patients of the doctors carrying them
out and, apart from the early phases of studies, they do not usually receive any form of
monetary compensation. For all of these reasons, the relationship between the researcher
and the participant more closely resembles the doctor-patient relationship than the
employer-employee one. Thirdly, although some of the benefits produced by clinical
trials are universal in character (patent royalties, for example), the benefits of direct
relevance to participants (health care services and interventions shown to be beneficial)
are particular in nature, meaning they cannot be replaced by their equivalent in other kind
of benefit. For example, if the participants of a study are entitled to $ 10 each, they can
receive with their consent an alternative benefit worth $10 without loss on their part. But
                                                            
32
Sabbagh, op. cit., 258.
33
Ibid., 259.
34
Ibid., 263.
35
Ibid., 261.
36
Loc. cit..
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if the participants are entitled to receive antiretroviral treatment X, there will not be an
alternative benefit they can receive, except for an antiretroviral treatment Z which is as
effective as X for that person. In any case, the price of X or Z is not the main issue for the
participants, but rather the efficiency of the treatment they receive. This being the case,
the application of the principle of justice as mutual benefit defended by the fair benefits
model would not appear to be favored by the attributes of the social context in which
collaborative international clinical trials take place, in particular with relation to post-trial
access. Further study will be required to determine a more appropriate principle.

Conclusion

This study has attempted to show that the principle of post-trial access as set out in the
2008 Helsinki Declaration is open to both robust and permissive interpretations. The
2008 declaration is, therefore, true to its time, being marked by the tension present in the
debate on the question of justice in clinical research carried out in developing countries, a
debate which forms but a part of the more profound and difficult debate on global justice.
This study has also sought to defend a robust interpretation of the principle of post-
trial access and made preliminary arguments for the application of a conception of justice
different from that assumed by the fair benefits model. Finally, the study has identified
the need for more work on the identification of an adequate model of benefit sharing for
the social context of international collaborative clinical research.

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