S5-1 Requena DoH Vatican
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Access to Benefits
Between the Categorical Imperative and Solidarity
Prof. Pablo Requena
Pontificia Università Santa Croce
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“More work is needed”
Philippines Manila Research Ethics Board
› 193 protocols
› 2012-2017
Jimenez EB, Virtudazo JMP
, Torres CE, Bernabe R dlC. Availability of post-trial access in clinical trials: a review
of clinical trial protocols submitted to the research ethics board of the University of the Philippines Manila.
Curr Med Res Opin. 2019;35(11):1849-1855
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“More work is needed”
Philippines Manila Research Ethics Board
› 193 protocols
› 2012-2017
“To date, none of the clinical trial protocols evaluated by
UPMREB fully complied with ethical requirements for PTA”
Jimenez EB, Virtudazo JMP
, Torres CE, Bernabe R dlC. Availability of post-trial access in clinical trials: a review of
clinical trial protocols submitted to the research ethics board of the University of the Philippines Manila. Curr Med Res
Opin. 2019;35(11):1849-1855
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The ethical question
What moral obligations do study sponsors have regarding
participants once the experimentation is concluded?
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Ethical question
What moral obligations do study sponsors have regarding
participants once the experimentation is concluded?
› Is it obligatory to provide the research product if proven beneficial for patients, or is it
merely optional?
› Who should ensure compliance?
› For how long should this access be guaranteed?
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Outline
1. Some data
2. Central ethical issue
3. Suggestions for the Declaration of Helsinki
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Conclusion… in advance
› There is a moral obligation to share the benefits
› In many cases, the sharing of benefits means ensuring
access to effective drugs
› Work towards a change in the “culture”
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1. Some data
› Major pharmaceutical companies
› Difficulty in collecting good examples of PTA
› Confirms the exceptional nature of PTA
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› European Clinical Trials Register (EUCTR): 2014
› 1624 studies in 21 countries
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› European Clinical Trials Register (EUCTR): 2014
› 1624 studies in 21 countries
› No provisions for PTA
• 54% high income countries
• 38% low-middle income countries
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› European Clinical Trials Register (EUCTR): 2014
› 1624 studies in 21 countries
› No provisions for PTA
• 54% high income countries
• 38% low-middle income countries
› In many cases “PTA provision” was providing
information
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› Majority of investigators were not aware of the ethical
obligation of PTA.
• 7 studies before 2000
• 17 studies after 2000
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› Majority of investigators were not aware of the ethical
obligation of PTA.
• 7 studies before 2000
• 17 studies after 2000
› None of the works mention PTA in the publications.
› After 2000:
• 35% adherence to DoH
• 82% consider PTA “in some way”
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› majority of investigators were not aware of the ethical
obligation of PTA.
• 7 studies before 2000
• 17 studies after 2000
› None of the works mention PTA in the publications.
› After 2000:
• 35% adherence to DoH
• 82% consider PTA “in some way”
› In many cases “PTA provision” was providing information
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› 2011-2012
› 33 products in US market; 8 in all Latin-American countries
› Only 1 product had a price lower than the country’s
monthly minimum wage
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› 34 studies (2003-2004)
› None of the cases studied included the option of accessing
the medication after the study
• 100 (51.81%): some PTA reference
• 93 (48.19%): PTA did not apply
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What did they understand by PTA?
1. Existence of standard care outside the trial
2. No provision of the study drug after the trial
3. Unknown benefit due to the experimental nature of the
study
4. The drug is available on the market or will be
manufactured
5. Access to the study drug during the study
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1. Some data: conclusions
PTA is rarely considered today
› High percentage of protocols:
• Do not consider PTA
• State that it does not apply in their case
• Mention types of PTA that contradict what is present in ethics
› In the majority of cases, PTA is limited to sharing information
› Unclear policy in many pharmaceutical companies
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2. Central moral question
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2. Central moral question
Belmont Report (1978)
“research should not unduly involve persons from groups
unlikely to be among the beneficiaries of subsequent
applications of the research” (Part B, 3. Justice)
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2. Central moral question
› A matter of justice
› The debate about “exploitation”
› “Addressing Exploitation: Reasonable Availability Versus
Fair Benefits“ (Ezequiel Emmanuele, 2008)
› Not every lack of PTA constituted exploitation
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2. Central moral question
“Hierarchy” in morality:
1. Injustice as “exploitation”
2. Injustice that does not entail “exploitation”
3. No “real” injustice
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2. Central moral question
The culture or vision driving the experimentation
› Primarily profit-driven
› Strong solidarity dimension
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2. Central moral question
The culture or vision driving the experimentation
› Primarily profit-driven
› Strong solidarity dimension
Justice is necessary but it is not sufficient
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3. Suggestions
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One more difficulty: rule for most or all cases…
• Challenging for law
• “Impossible” for ethics
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One more difficulty: rule for most or all cases…
• Challenging for law
• “Impossible” for ethics
Normative ethics vs. Virtue ethics
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22. The design and performance of each research study
involving human subjects must be clearly described and
justified in a research protocol.
(…)
In clinical trials, the protocol must also describe
appropriate arrangements for post-trial.
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26. In medical research involving human subjects capable
of giving informed consent, each potential subject must be
adequately informed of the aims, methods, sources of
funding, any possible conflicts of interest, institutional
affiliations of the researcher, the anticipated benefits and
potential risks of the study and the discomfort it may
entail, post-study provisions and any other relevant aspects
of the study.
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Post-Trial Provisions
34. In advance of a clinical trial, sponsors, researchers and
host country governments should make provisions for
post-trial access for all participants who still need an
intervention identified as beneficial in the trial. This
information must also be disclosed to participants during
the informed consent process.
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The “simplest” suggestion: substitute “should” with “must”.
34. In advance of a clinical trial, sponsors, researchers and
host country governments must make provisions for post-
trial access for all participants who still need an
intervention identified as beneficial in the trial. This
information must also be disclosed to participants during
the informed consent process.
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Another suggestion: negative way
34. No clinical trial ought to commence without explicit
provisions established by sponsors, researchers, or host
country governments to ensure post-trial access for all
participants requiring an intervention recognized as
beneficial during the trial. This information must also be
disclosed to participants during the informed consent
process.
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Corollary
› No protocol should be approved for a country (or an area
within the country) when an effective and necessary drug
cannot be provided to research participants after the trial
› Ethics Review Committee
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