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 However, because of inadequate, inconsistent, and outdated information, SmPCs are not appropriate for providing the suggested information to patients [29].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.