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Post-trial access to drugs for rare diseases: an integrative review



This study is an integrative literature review to analyze the scientific production about post-trial drug access by participants of clinical trials for rare diseases. The search was carried out in the Virtual Health Library, Embase, PubMed, SciELO, Scopus and Web of Science databases, covering 21 studies. Two categories emerged from the analysis: clinical research with orphan drugs and market regulation; and access to orphan drugs: background, globalization and the right to health. The first analyzes issues related to the number of patients with rare diseases, the efficacy and safety of these studies and the cost and price of medications. The second addresses the historical background of post-trial access, the globalization of clinical trials and the difficulties to ensure the right to post-trial access to orphan drugs. Few articles addressed post-trial drug access by participants with rare diseases as a central issue, which points to the importance of further studies on this subject.
662 Rev. bioét. (Impr.). 2022; 30 (3): 662-77
The authors declare no conict of interest.
Rev. Bioét. vol.30 no.3 Brasília Jul./Sep. 2022
Revista Bioética
Print version ISSN 1983-8042 | On-line version ISSN 1983-8034
Post-trial access to drugs for rare diseases:
an integrative review
Jeerson Westarb Mota 1, Fernando Hellmann 1, Jucélia Maria Guedert 2, Marta Verdi 1, Silvia Cardoso Biencourt 3
1. Universidade Federal de Santa Catarina, Florianópolis/SC, Brasil. 2. Hospital Infanl Joana de Gusmão, Florianópolis/SC, Brasil.
3. Secretaria de Estado da Saúde de Santa Catarina, Florianópolis/SC, Brasil.
This study is an integrave literature review to analyze the scienc producon about post-trial drug
access by parcipants of clinical trials for rare diseases. The search was carried out in the Virtual
Health Library, Embase, PubMed, SciELO, Scopus and Web of Science databases, covering 21 studies.
Two categories emerged from the analysis: clinical research with orphan drugs and market regulaon;
and access to orphan drugs: background, globalizaon and the right to health. The rst analyzes
issues related to the number of paents with rare diseases, the ecacy and safety of these studies
and the cost and price of medicaons. The second addresses the historical background of post-trial
access, the globalizaon of clinical trials and the dicules to ensure the right to post-trial access
to orphan drugs. Few arcles addressed post-trial drug access by parcipants with rare diseases as
a central issue, which points to the importance of further studies on this subject.
Keywords: Ethics, research. Rare diseases. Bioethics. Clinical trial.
Acesso a medicamentos para doenças raras no pós-estudo: revisão integrava
A m de analisar a produção cienca acerca do acesso a medicamentos no pós-estudo por parcipantes
de ensaios clínicos com doenças raras, realizou-se revisão integrava da literatura nas bases Biblioteca
Virtual em Saúde, Embase, PubMed, SciELO, Scopus e Web of Science, abrangendo 21 estudos.
No processo analíco, surgiram duas categorias: pesquisa clínica com drogas órfãs e regulação do
mercado; e acesso a drogas órfãs: história, globalização e direito à saúde. A primeira analisa questões
relavas à quandade de pacientes com doenças raras, à ecácia e à segurança dessas pesquisas e
aos custos e preços dos medicamentos. A segunda trata do panorama histórico do acesso pós-estudo,
da globalização dos ensaios clínicos e das diculdades para efevar o direito ao acesso a drogas órfãs
no pós-estudo. Poucos argos abordaram o acesso ao medicamento no pós-estudo por parcipantes
com doenças raras como questão central, o que aponta a importância de mais estudos sobre esse tema.
Palavras-chave: Éca em pesquisa. Doenças raras. Bioéca. Ensaio clínico.
Acceso a medicamentos para enfermedades raras en el posestudio: una revisión integradora
Se pretende analizar la producción cienca sobre el acceso a medicamentos para enfermedades raras
en el posestudio a parr de una revisión integradora en las bases de datos Biblioteca Virtual en Salud,
Embase, PubMed, SciELO, Scopus y Web of Science, que encontraron 21 estudios. Surgieron dos
categorías en el análisis: invesgación clínica con medicamentos huérfanos y regulación del mercado;
y acceso a medicamentos huérfanos: historia, globalización y derecho a la salud. La primera examina
el número de pacientes con enfermedades raras, la ecacia y seguridad de los estudios, así como los
costes y precios de los medicamentos. La segunda aborda el panorama histórico del acceso posestudio,
la globalización de los ensayos clínicos y las dicultades para materializar el derecho al acceso
a medicamentos huérfanos en el posestudio. Pocos estudios plantean el acceso a estos medicamentos
en el posestudio, y son necesarios más estudios sobre el tema.
Palabras clave: Éca en invesgación. Enfermedades raras. Bioéca. Ensayo clínico.
Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
Rare diseases aect a signicant percentage
of the populaon, which reveals an important
health issue regarding the availability of
treatment and the ethical aspects related to
research and the need for public policies for these
individuals 1-3. Also known as orphan diseases,
such pathologies mainly aect children. Diseases
that aect 65 people per 100,000 
are classied
as rare. When they aect one paent in every
50,000 people, they are dened as very rare,
ultra-rare or super-rare 7.
There is no consensus on the number of rare
and ultra-rare diseases 8. However, it is esmated
at around 8 thousand, accounng for a quarter
of all known diseases worldwide. Most of these
pathologies have a genec origin, unlike others
such as cancer and infecous, toxic and chronic
diseases. Global infant mortality among people
with rare diseases reaches 30%. This percentage
is greater in peripheral countries such as Brazil,
where diagnosis and access to experimental
clinical research and to potenal therapies from
this process are decient 8.
By its nature, an experimental clinical trial is
not the same as a treatment and, in the case of
rare diseases, the search for therapies and the
belief in a cure can lead to therapeuc mistakes.
In this sense, normave standards for research
ethics in clinical trials of this type must be
transparent and based on documents that regulate
and guide research governance 9.
The process of searching for so-called
orphan drugs consists of clinical trials
aimed at developing safe therapies for such
. The development of these
drugs is benecial to the area of unmet needs;
however, the pharmaceucal industry has lile
interest in developing and markeng them 
In addition, this process must be based on
internaonally established ethical foundaons
so that the design and practice of research
are fair, especially in relaon to drug supply 12,13.
The guarantee of access to beneficial
interventions by participants of a clinical trial
aer its compleon is called post-trial access14.
This principle appears internaonally from the
year 2000, in the Declaraon of Helsinki (DH)
of the World Medical Association (WMA) 15,
a guiding framework for Brazilian ethical standards,
which aim to ensure the rights of research
parcipants in relaon to scienc objecves,
during or after the clinical trial 16. However,
the latest version of DH, dated 2013, has not been
applied to research in Brazil and the country’s
current ocial documents do not menon it for
disagreeing with its posions regarding the use
of placebos and post-trial access.
In this context, the Brazilian Naonal Research
Ethics Commiee/Research Ethics Commiees
(CEP/Conep) system is responsible for evaluang
human research ethics in Brazil and has
advanced the defense of the rights of Brazilian
research parcipants, especially for being part
of the social control framework of the Unied
Health System (SUS) 17.
The standard that broadly covers the issue of
post-trial access is Resoluon 466/2012 of the
Naonal Health Council (CNS), which approves
guidelines and regulatory standards for research
with humans. In Item III.3, this resoluon provides
that research with humans should:
d) ensure that when the study is over, the sponsor
grants all parcipants free and indenite access to
the best prophylacc, diagnosc and therapeuc
methods that have proven to be eecve;
d.1) access will also be guaranteed in the interval
between the end of individual parcipaon and the
end of the study, in which case said guarantee may
be given through an extension study, according
to a duly jused analysis of the parcipant’s
aending physician 18.
Conep’s resoluons on research ethics also
apply to rare diseases, and the resolutions
of the Collegiate Board (RDC) of the Naonal
Health Surveillance Agency (Anvisa) regulate the
availability of drugs for people with rare diseases
that have not yet been approved to be marketed
in Brazil. For example, RDC 38/201319 addresses
expanded access, compassionate drug use and
post-trial access in general, and is not specic to
rare diseases. This resoluon was amended in
October 2019 by RDC 311/2019 20, which refers
the issue of the provision of post-trial drugs
to Conep resoluons.
664 Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
CNS Resoluon 563/2017 21, in turn, specically
addresses post-trial access to drugs for ultra-rare
diseases, that is, it does not apply to rare diseases.
With this resoluon, mandatory post-trial access,
previously unrestricted, indefinite and the
exclusive responsibility of the industry, is now
restricted to five years, counted from the
denion of the price in reais by the Drug Market
Regulaon Chamber (CMED).
Currently, Bill 200/2015 22, which has been
approved by the Federal Senate and is being
debated as Bill 7082/2017 23 in the Chamber
of Depues, calls into queson the protecon
of research parcipants in Brazil by proposing
new resoluons for Brazilian research from an
ethical-normave point of view, posing a threat
to the right to post-trial access 24.
The production of drugs for rare diseases
must be seen as a government issue to avoid the
imposition of a capitalist and market-oriented
view. Faced with the specificities of rare and
ultra-rare diseases, added to the forces that tend
to minimize the role of the state and maximize
the health market, the market for limited use
drugs presents ethical conflicts that evidence
the collapse of public interests in relation
to private ones.
This arcle analyzes the scienc producon on
access to post-trial drugs by parcipants in clinical
trials for rare diseases.
The integrave review 25-32 consisted of six steps:
1. Idencaon of the problem;
2. Sample selecon;
3. Categorizaon of selected studies;
4. Crical analysis of the studies included in
the review;
5. Descripon of results;
6. Interpretaon and discussion of results in order
to gather and synthesize exisng knowledge
on the subject 31.
The guiding queson of the study was: “What
ethical issues are found in the literature on access
to pharmacotherapy by parcipants in clinical trials
for rare diseases?To answer it, a bibliographic
search was carried out in the following databases:
Virtual Health Library (VHL), Embase, PubMed,
SciELO, Scopus and Web of Science. The search
was adapted to the specicies of each database,
leading to the development of themac blocks
associated with Boolean operators:
Themac block 1: doenças raras,” “rare diseases,
“orphan diseases.
Themac block 2: éca,” “ethics,” “bioéca,”
“bioethics,” “pesquisa éca,” “ethical research.”
Themac block 3: acesso ao pós-estudo,”
“post-trial access,” “access to post-clinical trial,”
“post-trial responsibilies, “post-trial obligaon,”
“access to pharmaceucals,” “access to medicines
and health technologies,” “access to essenal drugs
and health technologies.
A reverse exploratory search was carried out based
on studies found during the inial search process.
The inclusion criteria were studies published
as scienc papers (original or review), in any
language, between 2000 and 2020. Theses,
dissertaons, essays, reviews, books or abstracts
of proceedings of scienc events were excluded,
in addition to works published outside the
established me frame.
Clarivate Analycs’ EndNote X8 soware was
used as an auxiliary tool to build databases and
select papers. Subsequently, the chosen studies
were analyzed and idened, as shown in the
owchart (Figure 1) of the data collecon process
according to the PRISMA method 33. The search
for papers was carried out between September
and October 2020.
In the inial step, the data were systemazed
into two categories determined a posteriori. In the
nal step, the data were discussed by grouping
criteria, compiling information and important
trends to address the theme.
Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
Figure 1. Flowchart of the study selecon steps of the integrave review (2021)
Excluded studies
Studies excluded aer
screening by reading
tle and abstract
n= 179
Studies included aer
screening by reading
tle and abstract
n= 62
Studies included
idenfied in the
reverse search
n= 2
Studies excluded
aer reading in full
n = 43
Number of studies included in the integrave review
Studies aer
eliminang duplicates
Number of studies found in the databases
The search in the databases resulted inially
in 464 studies, of which 241 remained aer the
exclusion of duplicates. Following the screening
of keywords, tle and abstract, 179 did not t
the theme, leading to a total of 62, which were
read in full, resulng in 19 studies, to which were
added two works in the reverse search. The nal
sample consisted of 21 studies, according to the
proposed selecon criteria (chart 1).
Chart 1. Selected studies according to authors, year, country of origin, language, journal and database
Authors no. Year Country/origin Language Journal/origin Database
Makady; 2020 12 12020 Belgium English Orphanet Journal
of Rare Diseases Scopus
Blin and collaborators;
2020 34 22020 France English Therapies
PubMed, Scopus,
Web of Science
Bouwman, Sousa,
Pina; 2020 11 32020 Portugal English Health Policy
and Technology
Embase, Scopus,
Web of Science
Dal-Ré and
collaborators; 2020 35 42020 Spain Spanish Anales de Pediatria PubMed, Scopus
Naud; 2019 16 5 2019 Brazil Portuguese Revista Brasileira de Bioéca Reverse search
666 Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
Authors no. Year Country/origin Language Journal/origin Database
Gelinas and
collaborators; 2019 36 62019 USA English Contemporary Clinical Trials Scopus
Saviano and
collaborators; 2019 37 72019 Italy English Sustainability Web of Science
Chaves Restrepo and
collaborators; 2018 38 82018 Colombia English Value in Health Embase
Pace and
collaborators; 2018 39 92018 Australia English Health Policy Scopus,
Web of Science
van Egmond-Fröhlich,
Schmi; 2018 40 10 2018 Austria German Monatsschri
Embase, Scopus,
Web of Science
Hasford, Koch; 2017 111 2017 Germany German
VHL, PubMed,
Web of Science
Spargo, Seoane-
Vazquez; 2017 41
12 2017 USA English Orphanet Journal of Rare
VHL, PubMed,
Web of Science
Mastroleo; 2016 42 13 2016 Argenna English Developing World Bioethics VHL, Scopus
Dallari; 2015 43 14 2015 Brazil Portuguese Revista Bioéca SciELO
Silva, Sousa; 2015 715 2015 Brazil Portuguese Caderno de Saúde Pública VHL, SciELO
Rhee; 2015 44 16 2015 USA English Ama Journal of Ethics VHL, Scopus
Rosselli, Rueda,
Solano; 2012 45 17 2012 Colombia English Journal of Medical Ethics Web of Science
Goldbaum; 2011 46 18 2011 Brazil Portuguese Revista da Associação
Médica Brasileira Reverse search
Barrera, Galindo;
2010 47 19 2010 Colombia English Advances in Experimental
Medicine and Biology
VHL, PubMed,
Web of Science
Boy, Schramm; 2009 48 20 2009 Brazil Portuguese Caderno de Saúde Pública VHL
Grady; 2005 49 21 2005 USA English Yale Journal of Health Policy,
Law, and Ethics
VHL, PubMed,
Web of Science
VHL: Virtual Health Library; USA: United States of America
Chart 1. Connuaon
Bibliometric data indicate the number of
studies published each year: four studies (19.1%)
in 2020; three studies (14.3%) per year in 2019, 2018
and 2015; two studies (9.4%) in 2017; one study
(4.8%) in 2016; one study per year in 2012, 2011,
2010, 2009 and 2005, totaling ve studies (23.8%).
Regarding the origin of the studies and
respecve authors, Brazil has ve (23.8%); United
States, four (19.0%); Colombia, three (14.3%);
and Germany, Austria, Argentina, Australia,
Belgium, Spain, France, Italy and Portugal,
one study each, totaling nine (42.9%). Regarding
the language of publicaon, 13 studies (61.9%) are
in English, ve are in Portuguese (23%), two are
in German (9.5%) and one is in Spanish (4.8%).
Based on content analysis, the studies were
grouped into two categories:
a. Clinical research with orphan drugs and
nancial market regulaon;
b. Access to orphan drugs: background,
globalizaon and the right to health, comprising
dierent themes (Chart 2).
Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
Chart 2. Categories, emerging themes and descripons idened in the arcles on rare diseases (2021)
Clinical research with orphan drugs and market regulaon
Emerging theme Descripon
Populaon of paents
with rare diseases
Small size of paent populaon; characteriscs of manifestaon and geopolical
distribuon of rare diseases converge on the problem of paent enrollment
in clinical trials (Annemans, Makady; 2020 12; Barrera, Galindo; 2010 47; Dallari; 2015 43;
Hasford, Koch; 2017 1; Rhee; 2015 44; Rodriguez-Monguio, Spargo, Seoane-Vazquez; 2017 41;
Rosselli, Rueda, Solano; 2012 45).
Ecacy and safety
Compliance with ecacy and safety requirements in clinical research of drugs
for rare diseases (Annemans, Makady; 2020 12; Barrera, Galindo; 2010 47;
Chaves and collaborators; 201838; Hasford, Koch; 2017 1; Pace and collaborators; 201839).
Cost and price
The high cost of the development and post-markeng of drugs for rare diseases
poses obstacles to access by the target populaon, revealing the industry’s
eorts to recover development costs, use of funding and judicializaon
to ensure access (Barrera, Galindo; 2010 47; Blin and collaborators; 202034;
Boy, Schramm; 2009 48; Dal-Ré and collaborators; 202035; Rosselli, Rueda, Solano; 2012 45;
Saviano and collaborators; 201937; van Egmond-Fröhlich, Schmi; 2018 40).
Market regulaon
The regulatory process for orphan drugs is carried out by regulatory bodies in each
country, somemes inuenced by paent organizaons, but market monopoly and price
elascity reveal regulatory aws that reduce access and favor prot. (Bouwman, Sousa,
Pina; 2020 11; Dallari; 2015 43; Rhee; 2015 44; Saviano and collaborators; 201937;
van Egmond-Fröhlich, Schmi; 2018 40).
Access to orphan drugs: background, globalizaon and the right to health
Emerging themes Descripon
Historical background
Internaonal and naonal documents/standards disseminate post-trial provision of
benecial orphan drugs (Dainesi, Goldbaum; 2011 46; Dallari; 2015 43;
Gelinas and collaborators; 201936; Grady; 2005 49; Mastroleo; 2016 42;
Naud; 2019 16; Silva, Sousa; 2015 7).
Globalizaon of
clinical trials
Contemporary evoluon of clinical trials through post-trial access to orphan drugs
(Boy, Schramm; 2009 48; Dainesi, Goldbaum; 2011 46; Grady; 2005 49; Mastroleo; 2016 42;
Rosselli, Rueda, Solano; 2012 45; Silva, Sousa; 2015 7).
Right to health Post-trial provision of orphan drugs as a right to health (Dallari; 2015 43;
Rodriguez-Monguio, Spargo, Seoane-Vazquez; 2017 41).
Clinical research with orphan drugs
The themes related to the development of
orphan drugs in clinical trials were addressed
by 17 papers. The authors comprehensively report
how the prevalence of rare diseases, which is lower
than those of other diseases, becomes representave
when they are grouped. The low prevalence
justifies the difficulty of recruiting participants,
spread around the world, and reveals problems in
quanfying the size of the populaon and ensuring
fair and equitable parcipaon in research 
Annemans and Makady 12 argue that the
incidence and prevalence of rare diseases can be
seen as a set of uncertaines, since the exact size
of the aected populaon, the characteriscs of
the subpopulaons and the clinical manifestaons
of the diseases are variable. Rodriguez-Monguio,
Spargo and Seoane-Vasquez 41 show that as there
is no consensus on the size of the populaon of
paents with rare diseases, praccal intervenon
on this dimension is necessary.
The authors also cross population growth
with the growth of the identification of new
rare diseases 41. The prevalence of the disease as
a promoter of the clinical development of orphan
drugs is problemazed, since it conicts with the
concept of jusce, as populaons usually tend
to grow, which, in percentage terms, would reduce
and exclude people with rare diseases over me 
668 Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
The scant and dispersed distribuon of rare
diseases in the population makes it difficult
to recruit for clinical trials (particularly in
phases I, II and III) the number of parcipants
required for the approval of any drug, including
orphan drugs. The authors also define this
populaon as vulnerable and unprotected when
it comes to access in peripheral countries 47,48.
Accessible participation in clinical trials of
drugs for paents with rare diseases requires
relevant policies and reflection, mainly from
the populaon point of view, to provide jusce
and equity 49. In this sense, Silva, Ventura and
Castro 50 discuss equal opportunies in the use
of healthcare services and access to clinical trials
for orphan drugs. This shows that the distribuon
of such opportunies is hindered by obstacles
related to geographic location and eligibility
criteria for study parcipants, with exclusions of
populaon groups in clinical trials and consequent
loss of benet.
In Brazil, Bill 231/2012 
provided the creaon
of the National Research Fund for Rare and
Neglected Diseases (FNPDRN), reserving 30%
of funds from the Health Research Promoon
Program, an important iniave to ght inequalies
in research fostered by the development of drugs,
vaccines and therapies for rare diseases. However,
the bill was vetoed in its enrety by President
Jair Bolsonaro in 2019 for allegedly compromising
the feasibility of said program and reducing private
interest in the maer 52.
When the principle of jusce is absent in clinical
trials for rare diseases, the consequence is poor
access to health care, as equitable distribuon
is affected by several issues, such as disease
prevalence, populaon size and characteriscs,
and research inclusion criteria 1,12,41,43-45,47.
Seeking distribuve jusce in the case of rare
diseases means quesoning the rules and format
with which this distribuon is done according to
the characteriscs of the populaon. For Boy and
Schramm 48, access to clinical research and drugs
to treat rare diseases in peripheral countries,
places with blatant social asymmetries and
inequalities, affects the vulnerable population
harshly. Those authors advocate the need for
legimate public policies based on the principle
of equity, guaranteeing formal equality.
In general, the arcles analyzed argue that the
ethical standards that guide the requirements of
ecacy and safety in the development of clinical
research and producon of drugs for rare diseases
must be respected 1,34,39,47. Ethical standards of
information, consent and conduct of studies
must be followed regardless of disease frequency 
Barrera and Galindo 47 add that research on
drugs for rare diseases must also strictly comply
with the requirements of efficacy and safety,
ideally at the lowest possible cost, as these drugs
will be used in highly vulnerable and unprotected
people. Treatment eect and durability must also
be provided, based on condence interval, group
heterogeneity, dosage and adverse events 12.
However, Blin and collaborators state that some
clinical trials that may not be ethical for frequent
diseases may be acceptable for rare diseases
[statement regarding lack of power due to small
number of available paents and heterogeneity,
short trials that do not address the most relevant
clinical outcome and early use of biomarkers before
their qualicaon…]. Otherwise, there is a risk that
new drugs will never be developed for complicated
rare diseases and that eorts will be concentrated
on relavely frequent diseases with a well-known
and controllable development pipeline 53.
This shows the need to cricize the defense
of easing of post-trial access, as it is essenal to
strengthen the perspecve of the right to access
as a right to health. This view is adopted by
Pace and collaborators 39 when they address the
ethical framework for the creaon, governance
and evaluaon of accelerated access programs,
presenting an overview of the case of rare
diseases. Accelerang the process of obtaining
orphan drugs, the authors argue, may have
built-in risks, whether physical (resulng from
adverse drug eects) or psychological 39.
In turn, Hasford and Koch 1 stress that
methodological limits in clinical research exist
regardless of whether it relates to rare or frequent
diseases and must be respected, showing the
importance of planning the study in the best way
possible so as to minimize harm.
Hasford and Koch 1 argue that an important
aspect in ethical evaluaon in clinical trials for
rare diseases is the biometric quality of the
study’s design, size, sample and stascal analysis,
Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
as weak methodologies proposed in clinical trials
with humans are considered unethical. Therefore,
there is a need to ensure methodological criteria
based on ethical standards that cerfy the ecacy
and safety of clinical trials in the development
of these drugs.
Several studies focus on such efficacy and
safety. Most argue that the research method
should be guided by ethical rigor. However, some
authors suggest that, on the other hand, ethical
rigor may limit clinical research, due to the very
heterogeneity of diseases 34. Such rigor must
ensure compliance with the requirements of
ecacy and safety in planned trials for common
diseases and, especially, the safety of parcipants
and respect for human rights. Malleability
and acceleration in the rare disease research
process put parcipants at risk.
For Blin and collaborators 34, clinical trials are
intervenon studies that aim to analyze and evaluate
one or more drugs in order to intervene in the
progression of a rare disease or a group of them,
implying high economic costs. The guarantee of
access to parcipaon in clinical studies and the
benets arising from them may be jeopardized by
commercial clinical research, and it is up to research
ethics and public health policies to problemaze
this issue 34,35,37,40,43,45,47,48.
The high prices of orphan drugs may reect
the need to recover development costs with
a small group of paents 
. However, Saviano and
collaborators 37 question whether those prices
fairly reect the costs incurred in development or
are aimed at generang prot. The fact is that all
clinical research is costly, which, in the case of rare
diseases, gives rise to an unregulated market 40.
In addition to the possible benefits, some
authors reflect on how patients have access
to multicenter clinical trials and orphan
drugs 35,48 (the debate on the responsibility for
guaranteeing the provision of the post-study
drug will be addressed in the second secon of
this paper). Thus, mechanisms such as funding and
judicializaon are menoned. The development of
clinical trials for rare diseases may be thwarted by
lack of funding, although there are alternaves.
Dal-Ré and collaborators 35 describe how
paents occasionally nance clinical trials through
crowdfunding. This mechanism has been used in
the United States for about 40 years and raises
ethical quesons, mainly because it priorizes
the research needs of wealthy people rather than
society as a whole. Self-nancing is also advocated
as long as ethical research requirements are met 35.
Boy and Schramm 48 address the search for
access to orphan drugs in developing countries and
use the example of Brazil, where many drugs already
approved in the European Union, United States,
Australia and Asian countries are not on the Ministry
of Health’s list of exceponal drugs, with provision
depending on judicializaon. The literature also
stresses that access via judicializaon to drugs
in experimental or non-approved phases may
pose risks to paents 54.
Although it can ensure fair access to drugs
by patients, judicialization implies costly and
ethically quesonable public spending, especially
in countries with scarce public resources for
health. The regulatory process for the producon,
development and control of orphan drugs
is usually done by competent bodies, such as
the Food and Drugs Administraon (FDA) in the
United States, the European Medicines Agency
(EMA) in Europe and Anvisa in Brazil. Despite the
extensive regulatory process required by these
bodies, Rhee 44 states that many orphan drugs
are currently available but not always accessible
due to their high cost.
The author points out that the lack of market
regulaon raises concerns about pharmaceucal
companies creang a monopoly that prevents
buyers from negoang prices 44. The combinaon
of monopoly and price elascity results from faulty
market regulaon, with drug producers seng
protable prices under pressure from investors.
The search for prot is evident in the behavior
of drug producers, showing that the economic
risk assumed, given the relavely small market for
orphan drugs, can be oset by nancial incenves
(exibilizaon, tax credits and patents), which
is observed especially in developed countries,
as stated by Dallari 43.
Paent organizaons, such as the European
Organizaon for Rare Diseases (Eurordis) in Europe
and the Naonal Organizaon for Rare Disorders
(Nord) in the United States, play important
roles in the field of rare diseases, mainly by
encouraging the development of research and
670 Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
providing funding 
. In addion, they work to raise
public awareness, collecng informaon, providing
support and informaon to those aected, keeping
paent records and networking with universies,
industry and health authorities. The analyzed
authors also emphasize that paent organizaons
can inuence standards and the problemazaon
of market monopoly 11.
Access to orphan drugs
The theme related to the provision of post-trial
orphan drugs was addressed in nine articles.
The authors reported that ethical aspects related
to research with humans are historically governed
by several documents.
Each author provides a documentary historical
background of correcons and incorporaons
of guiding ethical principles, identifying DH,
the Belmont Report, the International Ethical
Guidelines for Biomedical Research Involving
Humans Subjects, of the World Health
Organizaon (WHO), the Universal Declaraon
on Bioethics and Human Rights (UDBDH)
and the International Declaration on Human
Genec Data 
as the main documents
in guiding ethical research with humans. DH and
DUBDH are highlighted as regulaons that address
access to post-trial drugs.
HD is recognized worldwide as a benchmark
for ethical research 46. Silva and Sousa 7 explain
that access to post-trial technologies by
research participants has been problematized
since 2000. The authors reveal that DH
incorporated the principle of post-trial access
in clinical research in the 2000s—in its fifth
revision—and that such endorsement produced
differing interpretations. Therefore, WMA issued
a clarification in 2004, triggering the debate on
post-trial access in interventions that proved
to be beneficial 7,16,36,42,43,46,49.
The latest version of DH 55, revised in 2013,
concisely addresses this principle, explaining
in Arcle
34 the need for provisions, agreed
between sponsors, researchers and governments
of the host countries of the clinical research,
for post-trial access to all participants who
sll need intervenon idened as benecial
in the study. DH recommends that relevant
informaon during the informed consent process
and the study outcomes be disclosed to the
parcipants in the consent form 43.
Mastroleo 42 argues that the 2013 revision of
DH abandons the ambiguous language found in
previous versions and idenes the responsible
agents. However, the author cricizes the removal
of references to access to appropriate care
other than drug-related and to obligatory access
to post-trial informaon 42.
In Brazil, the evoluon of regulaons on post-
trial access began with CNS Resoluon 196/1996 
complemented by CNS Resoluon 251/1997 56,
which specifically addresses research for new
drugs, vaccines and diagnosc tests.
The Brazilian ethical regulaon that addresses
the principle of post-trial access currently in force
is Resoluon CNS 466/2012 18, which regulates
ethics in clinical research, protects research
participants and defines post-trial access as
a sponsor’s duty 17, 18 , 56 . The Naonal Policy for
Comprehensive Care for People with Rare Diseases
was only implemented in 2014 by Ordinance
199/20144, expanding previous restricve conduct
with a predominant focus on medicine.
Grady 49 and Dainesi and Goldbaum 46 consider
the issue of the principle of post-trial access
a challenge, revealing that it has been a subject
of discussion since the late 1980s, when it was
associated with the connuity of treatment of
parcipants in HIV/AIDS studies. Other arcles also
address the development of anretrovirals 57-63.
International and national regulations reveal
an extensive debate on the incorporation of
the principle of post-trial access.
Naud 16 addresses the complexity of this
debate, revealing that regulaons are not capable
of covering all types of diseases. The author also
points to the fact that all research must have its
own evaluaon, based on the singularies of each
disease, populaon and their needs 
. The posion
defended by Naud 16 is considered to relate to
the “easing” of ethical research standards based
on those singularies.
Dainesi and Goldbaum 
view the disseminaon
of the principle of post-trial access as a contemporary
concern, especially in the context of other illnesses.
It is noted that the organizaon of HIV paents
played a role in inducing this principle, which gained
Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
momentum when it was inserted in HD in 2000.
In the case of the provision of orphan drugs to
parcipants with rare diseases, usually chronic and
progressive, the challenges relate to a specic context
that hinders access to medicines.
Different authors address the effect of
globalization on the expansion of clinical
research 42,46,49. For Dainesi and Goldbaum 46,
globalizaon raises new quesons in the scienc
community and the principle of post-trial access
emerges as a demand in this period. Similarly,
Mastroleo 42 states that providing the transion
of research parcipants to appropriate health
care when the study ends is a global problem.
Thus, continuity of medical care, including
treatment, is based on an ethical responsibility
to compensate volunteering participants who
subjected themselves to clinical research biases 46.
Before the 1980s, development of drugs for
rare diseases was insufficient and focused on
palliative measures that aimed to circumvent
the seriousness of those diseases 7. At that me,
inial concerns emerged about methodological,
regulatory and ethical aspects in the development
and producon of orphan drugs. Reecng on
the healthcare aspect of post-trial access in that
period was remarkably hypothecal.
The scientific development that enabled
the creation of enzyme and gene therapies,
which are the basis of most drugs for rare diseases,
was boosted aer the 1980s. Boy and Schramm 48
point to a contemporary evoluon of clinical
trials based on biotechnical, scienc progress,
which can be seen in current pharmaceucal
research of drugs for rare diseases.
The authors also state that the global
inseron of orphan drugs occurred progressively,
with developed countries as pioneers, and explain
that drugs are currently being developed for
paents with rare diseases, but with a focus on
economic aspects. The rarity of the disease and
the prevalence in peripheral countries slow down
development for purely protable reasons 48.
Dainesi and Goldbaum 46 reveal that clinical
trials of rare diseases and treatment with orphan
drugs aer the conclusion of a research require
attention particularly in developing countries,
where parcipants are more vulnerable. This ethical
issue relates to social condions that interfere with
the autonomy of the invesgated subjects, pung
their interests at risk.
Rosselli, Rueda and Solano 45 analyze the
situation of social vulnerability in developing
countries in research on mucopolysaccharidosis VI.
This rare disease aects indigenous ethnic groups
in Colombia, where access to developed drugs
is compromised by geographic marginalizaon
and frequent instuonal distrust.
Dallari 43 menons that the need to provide
ethical protecon in developing countries must
go beyond research parcipants to benet the
community. Dainesi and Goldbaum 46 state that
adequately designed and conducted clinical
research, with methodologies that comply with
maximum ethical rigor, must be extended to
the enre community.
Mastroleo 42 stresses that access to post-trial
orphan drugs is not just a problem for countries
with few or average resources. The author
highlights cases of uninsured or underinsured
research parcipants in the United States and of
former parcipants of clinical trials in the United
Kingdom whose therapy was not provided by the
United Kingdom Naonal Health Service (NHS) 42.
In a 2003 editorial, the scientific journal
The Lancet 64 states that parcipants from wealthy
naons are usually able to obtain the best available
treatment at the end of a clinical trial, while in the
developing world researchers leave the respecve
countries where the research was conducted and
the parcipants may be le with nothing. It adds that
the obligaon to provide post-trial access is closely
linked to the vulnerability of the parcipants.
In analyzing the distribuve jusce of post-trial
drugs in Brazil, Deucher 65 observed, based on
a qualitave and exploratory study, that paents
with serious and life-threatening diseases do
not suffer negligence in access to post-trial
drugs. The author also highlighted that foreign
pharmaceutical companies without national
representaon have diculty understanding the
need to provide post-trial drugs.
Therefore, it is perhaps appropriate to
reect that pharmaceucal mulnaonals and
conglomerates choose to ignore the problems
of countries with few resources, especially in
terms of social vulnerability. Dallari 43 argues that
the world community must remain commied
672 Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
to providing access to necessary health care
and treatment, especially post-trial access.
The globalization of clinical trials for rare
diseases is currently growing and sheds light on
ethical issues that guide post-trial access to orphan
drugs, both in peripheral and rich countries.
It is noted that the outsourcing of clinical trials
to peripheral countries is marked by economic
issues that oen hinder the right of access to
post-trial drugs by research participants who
need them. In this context, the right to health
supports the fundamental guarantee of post-trial
access to orphan drugs 41,43.
Dallari 43 analyzes the ethical conict involved in
post-trial access and in rare diseases, showing that
essenal products, such as orphan drugs, cannot
be viewed solely from the point of view of health,
as they are associated with predominant social,
economic and technological factors.
The constuonal law of Western countries
oen includes the right to life as one of its basic
moral principles. Based on that and on DUBDH,
Rodriguez-Monguio, Spargo and Seoane-Vasquez 41
proposed that the above-stated principle can
be understood as a right to health when related
to the use of orphan drugs in the treatment of
potenally fatal diseases. That makes it possible
to analyze the right of access to orphan drugs
as part of the right to health.
Thus, the state fullls its constuonal duty to
protect the right to health when it regulates clinical
research, creang dues between sponsors and
researchers and thereby protecng parcipants
entering in an asymmetrical relationship of
informaon and power that subjects them to high
risk. It is in this perspecve that the obligaon
to ensure post-trial access must be understood,
a condion that must be guaranteed by the state
within the scope of its duty to protect, and not
as a means of exempng itself from the duty
to provide. Access to post-trial orphan drugs is
considered a right of access to medicine, regardless
of how that access is made possible.
Final considerations
During the process of reading and composing the
categories resulng from the bibliographic survey,
issues emerged that address not only post-trial access
to drugs by parcipants aected by rare diseases,
but also questions about clinical research with
orphan drugs. Although this theme, congured in
the rst category, does not directly address the main
theme of the research, it is nevertheless relevant
to a comprehensive understanding of post-trial
access to orphan drugs.
The reduced size of the populaon of paents
with rare diseases is a factor that narrows down
the discussion of post-trial drug access, given that
the production of orphan drugs is basically
market-oriented rather than guided by the health
needs of that population. The geopolitical
distribuon of these diseases also encourages
discussion about the issue of enrolling in clinical
trials and increases global asymmetries. The high
costs of the producon of orphan drugs and their
reduced and unregulated market are obstacles
to guaranteeing post-trial access and favorable
to industry prots.
Although this is a relatively recent issue,
dierent regulaons address in dierent ways
specic quesons about the principle of post-
trial access by parcipants in research with rare
diseases, and there is no internaonal consensus
on the provision of orphan drugs to paents who
need them. Furthermore, it was observed that the
globalizaon of clinical trials is due to commercial
interests, especially to lower the costs of drug
development. This economic factor is another
barrier to post-trial access to orphan drugs.
Lastly, the authors address the right to health
and the right to life as principles that guide and
defend the right to post-trial access. In Brazil,
post-trial access to researched products is ensured
by ethical regulations in unequivocal and non-
negoable terms. In mes of budget cuts in the
health area, the only sure way to guarantee this
right to Brazilian cizens with rare diseases who
are volunteers in clinical research is to ensure that
the sponsor connues providing them with the
medicaon that benets them for as long as needed.
Discussions on research ethics from the
perspecve of social jusce contribute to ensure
the right to post-trial drug access, insofar as they
highlight the need for public policy in this regard.
It is therefore essenal to reect and take a stand
against threats that may place that right in jeopardy.
Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
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Rev. bioét. (Impr.). 2022; 30 (3): 662-77
Post-trial access to drugs for rare diseases: an integrative review
Jeerson Westarb Mota – Master – je
Fernando Hellmann – PhD –
Jucélia Maria Guedert – PhD –
Marta Verdi PhD –
Silvia Cardoso Biencourt – PhD – scb
Fernando Hellmann – Departamento de Saúde Pública. Campus Universitário Reitor João David
Ferreira Lima, s/n, Trindade CEP 88040-900. Florianópolis/SC, Brasil.
Participation of the authors
Jeerson Westarb Mota conceived the arcle. Fernando Hellmann and Jucélia Maria Guedert
helped design the study and write the arcle. Marta Verdi and Silvia Cardoso Biencourt
crically reviewed the text.
Received: 3.1.2021
Revised: 8.10.2022
Approved: 8.15.2022
ResearchGate has not been able to resolve any citations for this publication.
Full-text available
Doença ultrarrara é definida como doença debilitante ouque ameace a vida, com incidência menor ou igual a 1 (um) casopara cada 50.000 (cinquenta mil) habitantes. Várias normativasnacionais e internacionais já discutiram a obrigação do fornecimentodo medicamento de estudo que se mostrou mais eficaz em testeclínico a todos que participaram do estudo é um tema que provocadiscussão. No Brasil, recentemente a Resolução CNS nº 563 foipublicada e regulamenta o direito do participante de pesquisa aoacesso pós-estudo em protocolos de pesquisa clínica destinadosaos pacientes diagnosticados com doenças ultrarraras por um prazode cinco anos. O objetivo do presente artigo de revisão é apresentaressa resolução. Primeiramente, foram contextualizadas outrasnormativas internacionais e nacionais quando ao pós-estudo e emseguida a discussão acerca deste tema. A Resolução nº 563, de10 de novembro de 2017, é um importante progresso na proteçãodos participantes de pesquisa portadores de doenças ultrarraras,mas considerar o tratamento de doenças ultrarraras somente pelofornecimento de medicamento pós-estudo não é o mais adequado. Énecessária uma melhora em toda a rede estruturada de tratamentocomo Centros de Tratamento Especializados e uma política públicaefetiva para doenças ultrarraras com cobertura nacional.
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Resumen El desarrollo de medicamentos para ciertas enfermedades raras puede verse truncado por la falta de financiación. En estos casos, en ocasiones, los propios pacientes —o sus familiares— financian el ensayo clínico en el que recibirán el medicamento experimental. Hay 3 modelos de autofinanciación: 2 de ellos, «pagar por probar» y «pagar por participar», ya se han puesto en práctica; el tercero, el modelo «plutocrático», que ha sido recientemente planteado, es, hasta la fecha, un modelo teórico. En este trabajo se repasan los beneficios y riesgos científicos, sociales y éticos de los 2 modelos de investigación clínica: «pagar por participar» y el modelo «plutocrático». Una manera frecuente de poder autofinanciar estos ensayos clínicos es la obtención de fondos por micromecenazgo. Los aspectos más controvertidos de esta modalidad de financiación también son abordados en este trabajo desde diversas perspectivas. Por último, se plantea un escenario futuro que permitiera en nuestro país la puesta en marcha de estos ensayos clínicos autofinanciados mediante el modelo plutocrático.
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Background: Many treatments developed for rare diseases will have an Orphan Medicinal Product (OMP) designation, indicating that they are likely to deliver benefit in an area of high unmet need. Their approval may be based on a small or uncontrolled trial, as randomised controlled trials (RCTs) of sufficient size are often difficult to conduct, or repeat, as a result of the rarity of the condition, sparsity of patients, or for ethical reasons. Furthermore, many products are given a conditional marketing authorisation, requiring additional evidence to be collected after product launch. This is even more challenging with the advent of advanced therapeutic medicinal products, which use novel scientific approaches like gene or somatic cell therapy. Issue: Given the high unmet need associated with these products, there is pressure for Health Technology Assessment (HTA)/reimbursement bodies to enable rapid access to effective treatments. However, there is often only limited evidence available for assessment. Methods: TRUST4RD proposes an approach to identify uncertainties of most concern for decision-makers by developing an iterative and informed dialogue amongst stakeholders (including manufacturers, clinicians, patients, regulatory- and HTA agencies and payers), so that potential approaches to resolution can be discussed. As evidence is generated, uncertainties are reviewed and prioritised, and evidence-generation plans revised or clarified accordingly. The aim is to develop - both pre- and post HTA submission - a better understanding of evidence requirements versus evidence-generation trade-offs as an evidence base grows and the potential value of a product becomes clearer. Conclusion: TRUST4RD presents guidance on defining uncertainties and evidence gaps in the assessment of value and value for money of specialised treatments for rare diseases. It also provides guidance on the potential of Real World Evidence (RWE) to help address such uncertainties, including the typology of evidence uncertainties, the importance of different uncertainties and the data sources available to address them before and after HTA submission. In making use of the guidance, authorisation and reimbursement discussions on such treatments can be embedded in an evidence-rich context, thereby ensuring value to all parties, particularly to patients.
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Orphan medicines are medicinal products intended for diagnosis, prevention or treatment of life-threatening or debilitating rare diseases. They are ‘orphans’ because the pharmaceutical industry has little interest under normal market conditions in developing and marketing drugs intended for only a small number of patients suffering from very rare conditions. Successful development of new treatments for rare diseases and their sustainable patient access require overcoming a series of challenges related to research and health technology assessment. The orphan drugs legislation provides a set of incentives and conditions to the pharmaceutical industry to develop medicines for the treatment of rare diseases. In fact, the number of orphan products approved (centralized level) is far exceeding anything seen before the orphan drug legislation. However, the final stage relates to whether a patient is able to receive treatment in a timely and reimbursed manner occurs at the payers’ level (decentralized process), which, leads to inconsistency in patient access between European countries. The challenge of regulatory authorities, patient groups, pharmaceutical companies, legislators and payers is to provide access to new therapies, without geographic or economic discrimination. Despite the progress in the field of rare diseases there is still a need of investment. So, the main objective of this paper is to describe the regulatory framework of orphan medicines in the USA and the EU, including specific legislation and guidelines, orphan medicine designation process, economic encouragements and impact of these in market approval, to improve the consistency, effectiveness and sustainability of orphan medicines value assessment.
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Clinical trials for investigational new products to treat rare and ultra-rare diseases typically involve a limited number of research sites recruiting from a small pool of patients dispersed over a large geographical area. When remote access is not possible and participants must be present at a trial site, participation in research may require individuals and their families/caregivers to travel great distances, often at significant cost personally and financially and, frequently, for the duration of the trial. This article addresses the ethical and practical issues associated with the practice of sponsors offering financial and other assistance for relocation to trial sites from significant geographical distances, providing both foundational analysis of the ethical issues as well as actionable policy-level guidance on how to best approach these situations.
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Background: The bioethical debate in the world on who should pay for the continuity of post-trials treatment of patients that have medical indication remains obscure and introduces uncertainties to the patients involved in the trials. The continuity of post-trial treatment was only incorporated in the 2000s by the Helsinki Declaration. The Universal Declaration on Bioethics and Human Rights, published in 2006, points out that post-trial continuity may present a broader scope than just the availability of the investigated medicine. In the latest version of this Declaration, in 2013, it was stated that "prior to the start of the clinical trial, funders, researchers and governments of the countries participating in the research should provide post-trial access for all participants who still require an intervention that was identified as beneficial. This information should also be disclosed to participants during the informed consent process". However, a systematic review on the registration of phase III and IV clinical trials, from the clinical trials website, demonstrated that the understanding of the various guidelines and resolutions is conflicting, generating edges in the post-trial setting. For the health authorities of countries where clinical trials take place, the uncertainties about the continuity of the treatments generate gaps in care and legal proceedings against health systems, which are forced to pay for the treatments, even if they are not included in the list of medicines available to the population. Methods: Fifty-one representatives from the health, judicial, legislative, patient and academic organizations of eight countries of Latin American and South Korea took part in a meeting in Chile, in 2017, to discuss the responsibility of the treatment continuation after clinical trials. From a hypothetical case of development of a new drug and its studies of efficacy and safety, the participants, divided in groups, proposed recommendations for the problem and pointed out the pros and cons of adopting each recommendation. The groups were, afterwards, confronted by a simulated jury and, finally, issued a final recommendation for the problem. Then, an analysis was made on the content of the recommendations and the pros and cons in adopting conservative or liberal positions, besides the possible impacts of a restrictive regulation regarding the conduction of clinical trials, pointed out by the groups, before and after the simulated jury. Results: The theme was widely discussed and about 12 recommendations were proposed by the participants. The main ones took into account aspects related to patients' rights, economic factors and the development of new technologies, above the position of industry and research institutes, as well as the legislation in force in each country. Conclusion: The countries of Latin America and South Korea, currently, do not have laws that address patients' rights, moreover, there is no definition on who should be responsible for post-trial treatments. It is suggested that the World Health Organization issue a resolution recommending that all associated countries determine that the pharmaceutical and medical device industries, or those that sponsored it, should continue to provide treatment to all patients who participated in clinical trials and have medical indication to the continuity.
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This work is about how healthcare issues can be reframed from a sustainable and inclusive development perspective. Focusing on the case of orphan drugs and rare diseases, first, a country-based review of the main regulatory approaches to orphan drugs is conducted; then, the main contributions of the literature are reviewed to identify dominant views and the way the problem is more commonly framed. The main findings reveal that the dominant regulatory approaches and theoretical interpretations of the problem are mainly based on economic considerations. However, this does not seem to have led to very satisfactory results. Reflecting upon what the sustainability perspective can highlight with reference to healthcare, substantial connections between the orphan drugs issue and that of neglected diseases are highlighted. These connections suggest reframing the orphan drugs issue as a social equality and inclusiveness problem, hence the need to adopt a sustainable and inclusive development perspective. As a key sustainable development goal (SGD) to be shared by all nations, healthcare should always be approached by putting the principles of sustainable and inclusive development at the core of policy makers’ regulatory choices. Accordingly, we think that the orphan drugs issue, like that of neglected diseases, could be better faced by adopting a social equality and inclusiveness perspective.
Clinical development for orphan drugs is extremely demanding but fascinating. There is no single aspect that is really specific to it but instead it gathers most of the hurdles: design, outcomes, recruitment, Ethics, cost, probability and predictability for success. To overcome these difficulties, there has to be a great collaboration between academic centers, small and large pharma companies, patients’ representatives as well as health authorities to provide support and innovative approaches. The ultimate goal is to give access to patients with unmet medical needs to drugs with a favorable benefit-risk ratio. We review and discuss here the pillars for a successful clinical development for orphan drugs.
There are increasing demands on regulators and insurers internationally to provide access to medicines more quickly, and often on the basis of less robust evidence of safety, efficacy or cost-effectiveness than have traditionally been required. These demands arise from a number of sources, including those advocating for access to medicines for patients with life-threatening diseases, rare diseases, or subsets of common diseases and where entire populations are threatened in the context of public health emergencies. In response to these demands, policymakers have instituted a number of initiatives aimed at speeding up access to medicines, which we refer to collectively as "accelerated access" programs. While there are strong arguments for accelerated access programs, these programs also raise a number of socio-political, epistemic and moral issues. Some of these issues are common to all types of accelerated access programs, while others are specific to particular types of accelerated access. Here, we offer a conceptual framework that highlights ethically relevant similarities and differences among different kinds of accelerated access processes for the purpose of enabling ethically and politically-informed policy making.