Discussion
According to licensing regulations, approved licenses are valid for 5
years. There are no specific regulations about SmPCs, which are included
in the license application files and updated accordingly. Global
pharmaceutical companies update their licenses and SmPCs in a timely
manner when they have new information. However local and/or generic
companies do not update their licenses and SmPCs strictly according to
these rules. Furthermore, most discrepancies are observed in the case of
generic or older products.
When we evaluated the TMMDA-approved labels, we found that the labels
available were in accordance with those approved by other agencies,
mainly the EMA and FDA. The two major problems concerning the
pharmacovigilance information pertaining to the Turkish pharmaceutical
market are that generics may not have the same/similar information as
the original drugs and imported drugs lack information in Turkish for
the patient and/or for the prescriber.
Improvements in pharmacogenomics have enhanced its applications in
medical interventions. Therefore, it is necessary to disclose PGx;
however, the content communicated and the process of informing patients
about pharmacogenomics remains tentative [23]. Nevertheless, our
study reveals the fact that SmPCs are not standardized and do not
necessarily contain up to date information. A review of the literature
shows that this is not a local problem peculiar to some countries such
as Turkey, and is, in fact, a global problem [24-27]. SmPCs are
suggested as useful and effective tools for disclosing PGx [28].
However, because of inadequate, inconsistent, and outdated information,
SmPCs are not appropriate for providing the suggested information to
patients [29].
The scarcity of regulation pertaining to the PGx to be included in SmPCs
and standardized processes and the reluctance of pharmaceutical
companies in updating SmPCs have some widespread ethical implications
[27,30,31].
1. The first ethical implication is about the right of the patient to be
informed about the medication that is being given to the patient. The
right to have access to accurate and relevant information emerges from
the basic human right of autonomy [32]. Respect for autonomy is one
of the main principles of medical ethics and it is realized by
disclosing the necessary information to the patient and providing space
for patients’ decision-making without the undue influence of others.
Disclosure of information is a complex procedure that does not start and
end in one instance, but rather is an ongoing process that begins with
the interaction between the physician and the patient and continues
throughout the treatment. Patients may not be able to understand the
disclosed information in clinical settings, because several factors
might impede their cognitive capacity in that clinical setting or the
patients may have trouble recalling the disclosed information later when
they leave the hospital or need to refresh their memories upon achieving
an unexpected result with the medication [33,34]. Compared to other
medical information, PGx may be more confusing for patients. Thus, we
can assume it would be harder to understand or recall what has been
disclosed to patients [35]. SmPCs are useful references for patients
in this respect and should be regarded as a part of the process of
information disclosure to patients. Neglecting to update SmPCs hampers
the right of patients to have access to accurate information and
prevents them from exercising their autonomy.
2. Another ethical issue emerges from the principle of doing no harm to
the patient. SmPCs with outdated information may cause harm by
misleading patients about their medications. The principle of doing no
harm encumbers responsibility to all parties involved in health care
provision [32]. Pharmaceutical companies have a significant role in
health care services; hence, they are obliged to comply with the
principle of “do no harm” of medical ethics. The context of this
principle is not limited to not doing any intentional harm but has a
broader context to cover risk mitigation for the patient. Pharmaceutical
companies that provide SmPCs with poor content fail to acknowledge this
principle.
3. Not having adequate and consistent PGx in SmPCs poses a high risk for
harm among vulnerable groups such as children, the elderly, or pregnant
women. Since these population groups are considerably less subject to
clinical trials in pharmacogenomics, the accumulated scientific data are
limited. Moreover, a lack of clarity about the differences in
pharmacogenomic research for discovering medical interventions and
optimizing clinical care makes the provision of information to these
patient groups particularly important [36]. The pharmacogenomics
counseling skills for communicating with vulnerable populations and the
knowledge and interest of healthcare providers in new-found PGx are
variable and limited depending on their areas of expertise [37-39].
Hence well-written SmPCs may provide significant benefits and avoid harm
among these vulnerable groups.
4. Veracity and reliability are two important ethical values in clinical
ethics. Patients should trust that their healthcare providers will do
their best to benefit patients’ health. Trust in the physician is the
first ring in the chain and should be backed by trust in the health care
system and pharmaceutical companies. Trust is gained by veracity and
reliability between the parties. A lack of SmPCs or of SmPCs with
different content may harm the trust in health care agencies and
pharmaceutical companies by raising concerns about sloppy or inattentive
process management. It is plausible to argue that ruining patients’
trust in the healthcare system is another way of doing harm to patients,
which would impair the success of their treatment in the long term.
5. Patient empowerment is an essential component of personalized
medicine. Empowered patients play a new, more proactive, and leading
role in the management of their health status. Recently
direct-to-consumer (DTC) DNA testing companies have been offering PGx to
patients, and they will potentially be more at the forefront of
delivering personalized medicine in the near future [40]. Providing
PGx of drugs by means of SmPCs to patients presumably contributes to
patient empowerment by raising patients’ awareness about their medical
conditions and their proactivity during the course of treatments.
Based on the findings of our study, the standard of PGx in SmPCs is far
from that required for meeting these essential ethical requirements. It
is clear that an international organization such as the International
Council for Harmonization should act as a guide to make essential PGx
available and standardized globally. National agencies need to agree on
the definition of PGx and its levels. PharmGKB sets a good example in
this regard. After an agreement has been reached on the standardization
of PGx for inclusion in SmPCs, marketing license owners need to check
the approved labels, find discrepancies, and change labels accordingly.
Similarly, generic companies must be subject to the same requirements:
they should be required to update their SmPCs and other package inserts.
Following these simple recommendations will not only prevent the ethical
breach of patients’ rights but also will equip physicians to precisely
personalize the medicine being prescribed.