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Paumgartten FJR
388 Rev Assoc Med Bras 2017; 63(5):388-392
POINT OF VIEW
Ethical issues on the “synthetic” phosphoethanolamine clinical trial
Francisco José Roma Paumgartten1 *
1MD, PhD, National School of Public Health, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
Summary
Study conducted at the National School
of Public Health, Fundação Oswaldo Cruz
(Fiocruz), Rio de Janeiro, RJ, Brazil
Article received: 8/18/2016
Accepted for publication: 10/19/2016
*Correspondence:
Address: Av. Brasil, 4.036,
salas 101-104 e 913
Rio de Janeiro, RJ – Brazil
Postal code: 21040-361
Notwithstanding its approval by the National Committee for Ethics in Research
(Conep) on April 19, 2016, a trial of the so-called “synthetic” phosphoethanolamine
(syn-phospho) pill in cancer patients raises ethical concerns. An analysis by a
laboratory contracted by the Ministry of Science, Technology and Innovation
(MCTI) revealed that syn-phospho contained a great amount of impurities and
did not meet standards of pharmaceutical quality required for an investigational
drug. Cytotoxicity against human tumor cell lines and in vivo rodent xenograft
tumor assays consistently failed to demonstrate a potential anticancer activity of
syn-phospho. Preclinical safety studies of syn-phospho were also insufficient to
support a trial of this investigational drug in cancer patients. Moreover, the ethical
approval decision apparently overlooked two previous findings that suggested a
possible enhancement of mammary carcinoma cell proliferation by
phosphoethanolamine, and an apparent increase in lung metastases (rat implanted
tumor assay) by syn-phospho. The syn-phospho risk-benefit ratio is clearly
unfavorable and, thus, this trial in cancer patients does not fulfill a key requirement
to make a clinical research ethical. There are also concerns regarding whether the
study design is robust enough (scientific validity), and the social value of the trial
of syn-phospho in cancer patients is questionable.
Keywords: bioethics, clinical trial, investigational new drugs, neoplasms,
preclinical drug evaluation, risk-benefit assessment.
According to a nationwide registry of research in human
subjects , the Na-
tional Committee for Ethics in Research (Conep) cleared
a clinical trial protocol entitled: “Evaluation of safety
and efficacy of synthetic phosphoethanolamine in pa-
tients with advanced solid tumors” on April 19, 2016. A
further search on the National Agency of Sanitary Sur-
veillance (Anvisa) online registry of clinical trials (http://
torizados) indicated that the agency did not authorize
this new oncologic drug study in patients. As far as an
investigational drug is concerned, for the sake of best
protection of research subjects, clearance of clinical
research by both Conep and Anvisa is required. It is of
note that Anvisa is theoretically better equipped than
Conep for a thorough analysis of preclinical data and
clinical study protocols.
Furthermore, a bill that authorizes production, pre-
scription and consumption of syn-phospho as an anti-
cancer medication passed the Congress and the president
signed it into law (Law 13,269/2016) on April 13, 2016.
Since syn-phospho remains nearly untested for safety and
efficacy, this law represents an unprecedented shortcut
for a normally lengthy, costly and highly selective way to
develop and approve a new drug for marketing. The syn-
-phospho law was challenged by a lawsuit (Direct Uncon-
stitutionality Action) filed by the Brazilian Medical As-
sociation (AMB) and the full board of the Federal Supreme
Court (STF) suspended its efficacy until a final decision
by the court. The STF ministers who voted for a temporary
suspension of syn-phospho law cited the lack of clinical
studies in their declaration of vote.
Notwithstanding the approval by the Conep system,
the syn-phospho trial in cancer patients does not fulfill
at least three of seven key requirements to make a clini-
cal research ethical. These requirements to protect the
people participating in research (i.e., value, scientific
validity, fair subject selection, favorable risk-benefit ratio,
independent review, informed consent and respect to
enrolled subjects) are found in universally accepted codes,