Considering all these important international guidelines dealing with the ethical principles performing human studies, one might ask, do pharmaceutical medicine professionals need a specific professional ethical code. An in-depth consultation with the members of the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine (IFAPP) made it clear that many members supported the formulation of specific moral guidance. This can be understood appreciating that the profession extends far beyond clinical research. It includes drug regulation, advertising, pharmacovigilance, and the marketing of medicines, which need special attention and create special moral problems not at all or not adequately covered in medical ethics. In addition, the rapid scientific development constantly creates new ethical problems for the profession. In particular, the major campaign of human immunodeficiency virus-infected people for more rapid development and clinical availability of new drugs placed the scientific, marketing, and ethical problems of the pharmaceutical industry into the focus of society [15]. In addition, several examples of ethical misconduct in clinical trials carried out in developing countries by some pharmaceutical companies shook the confidence of the public in the professional behavior of the industry [16]. These problems led the IFAPP to set up a Working Party on Ethics in Pharmaceutical Medicine under the leadership of Dr. A.L. Becker at the 12th International Conference of IFAPP in 2002 [17]. The Working Party published the International Code of Ethical Conduct for Pharmaceutical Physicians in 2003 [18]. To understand the functional significance of the document, we present its structure and its main recommendations.

3.1 International Code of Ethical Conduct for Pharmaceutical Physicians (2003)

The IFAPP ethical code specifically seeks to provide guidance on moral issues for physicians working in the pharmaceutical industry and contract research organizations. The authors emphasize the most important moral message already in the preamble: “Pharmaceutical Physicians should recognize their ethical responsibility and stand aside from product loyalty when assessing factors affecting the product itself. They must remain aware at all times that the ultimate interests of both patients and their own employers are best served by an objective scientific attitude. The IFAPP recognizes that this may place a practicing Pharmaceutical Physician in a position, which demands considerable determination”. The conceptual architecture of the professional code was illustrated by comparing it to a Greek temple. The entire structure is based on universal principles of medical ethics. The columns supporting the Code of Ethical Conduct represent the specific core values of pharmaceutical medicine: the duty of care, competence and diligence, impartiality, probity, integrity, and accountability (Fig. 1). The more than 100 specific ethical recommendations are grouped into sections dealing with the core values. Several of them describe the care for the well-being of human subjects or deal with the management of clinical trials according to the accepted norms of medical ethics. Importantly, many comments discuss the intersection of medical care and industrial interests, which highlight the specificity of the pharmaceutical medicine profession. We primarily focus on these latter type of comments, which determine the unique characteristics of this professional code.

Fig. 1

Conceptual structure of the code of ethics. Medical ethics serves as the fundament, the major moral principles of pharmaceutical medicine support the International Code of Ethical Conduct [28, 41]

3.1.1 Duty of Care

In line with medical ethics, the care for the human subjects participating in a study is the primary obligation of the pharmaceutical physicians. In addition, they have to be responsible for designing trial protocols that are scientifically valid, respect the accepted codes of medical ethics, and prioritize the interests of the human subjects over the company. It is their duty to provide accurate and verifiable medical information for the company management and ensure that the interpretation of the findings accords with evidence-based medical knowledge.

3.1.2 Competence and Diligence

In addition to providing medical care, the pharmaceutical physicians have to contribute to the scientific and medical relevance and validity of clinical drug development plan. They must ensure that the scientific background of the human study is solid and sufficient data are available to make a reliable extrapolation of the expected safety of the planned intervention. They have to determine whether the methods applied in the study can provide high-quality data for the planned medical use, and whether the application of placebos is ethically appropriate. They must ensure that any possible scientific and ethical contradictions between the planners and the medical performers of the human pharmacology and clinical studies are timely resolved. They have to evaluate the medical and ethical needs of conducting studies on vulnerable populations, including children and the elderly, and when to initiate a drug trial on patients with rare diseases. Pharmaceutical physicians should pay also attention to the special local ethical, social, religious, and financial conditions that significantly influence the ethical responsibility of drug developers. They should not continue ongoing clinical studies or recommend the clinical use of new medicines until significant scientific doubt exists regarding their efficacy and safety. Furthermore, they should discourage any marketing exercise that is “masquerading” as a scientific study.

3.1.3 Impartiality

Pharmaceutical physicians must communicate all information gained in clinical studies correctly. Statements should not contain claims that cannot be justified. They should differentiate between providing information and therapeutic advice to patients. The latter should be the privilege of the treating physicians. Similarly “off-label” use of drugs should not be encouraged; however, this should not discourage them to communicate valid information on a file that might help the treating physician to use effectively and safely the medicine for a not registered indication.

3.1.4 Probity

Pharmaceutical physicians working in a commercial environment must exhibit high moral standards, personal integrity, honesty, and trustworthiness. Their work should not be skewed toward gaining either financial or scientific advantages. They should declare any conflicts of interests publicly. Probity means also the moral obligation to publish all study results supporting or contradicting the original hypothesis. Furthermore, a commercial interest should never take precedence over the duty to make timely and correct reports on adverse effects.

3.1.5 Integrity and Accountability in the Workplace

Pharmaceutical physicians usually work in larger teams when conducting clinical drug trials. They should encourage that possible differences in culture, religion, and gender should be handled fairly, protecting the human dignity of the coworkers. Mutual respect and good communication should underline cooperation. Malicious comments made by any coworker should not undermine the credibility of other team members.

3.2 IFAPP International Ethics Framework for Pharmaceutical Physicians and Medicines Development Scientists (PPs & MDSs*) [2nd Revised Edition of the International Code of Ethical Conduct for Pharmaceutical Physicians] (2018) [19, 20]

(* “In this text, MDS refers to experts in various fields of life sciences, pharmacy, and medical device engineering who have adequate training in non-clinical and clinical medicines development and work as integrated members of clinical medicines development teams.”)

The rapid development of science and the appearance of new technologies create many new moral problems for medicines development. It also rapidly breaks up traditionally established professional barriers. The cooperation of different professionals might frequently provide the best solution for many of these very complex scientific and ethical issues. We must appreciate, however, that an increased cooperation of various professionals might make moral decisions in various situations more complex and difficult. Some of the guiding ethical principles of the cooperating professionals might emphasize different solutions. The participants must in each situation analyze and understand both the common and occasionally different moral judgments of their partners for efficiently resolving conflicting views. To direct the attention to the need for broader professional cooperation, pharmaceutical physicians and medicine development scientists were both addressed in the title of the revised code. Jointly, we refer to these two groups as medicine development professionals.

The new title, Ethics Framework, indicates the second principal difference between the first and the revised documents. As was mentioned above, professions traditionally used their ethical codes for maintaining discipline in their community. Considering the increasingly complex moral problems arising in multi-professional medicines development, the authors felt it was more proper to replace the ethical code with the term ethical framework. The authors believe that this expression emphasizes that the goal of the document is the listing of moral advice to solve difficult ethical problems without enforcing preconceived mandatory ethical decisions. Finally, it is emphasized that the listed advice might be useful also to other physicians and scientists working in various organizations related to medicines development, for example, in human research ethics committees, regulatory agencies, and health technology groups.

The second edition retained the original structure of the document; the new recommendations were included into the earlier defined sections. Logically, many new entries referring to scientific development are presented in the section Competence and Diligence. Considering that translation medicine aims to closely link animal to human pharmacological studies, the authors of the framework extended the scientific-ethical responsibility in drug development also to researchers performing non-clinical animal experiments underlying directly human application. In addition, they emphasized that the molecular endpoints of clinical trials selected from laboratory research data must have sufficient construct validity and pathophysiological plausibility for providing a reliable basis for human studies. This is an outstandingly important obligation as unfortunately many non-clinical studies proved to be unreliable and not reproducible in practice [21,22,23]. The application of the concepts of translation medicine in modern drug development requires studies on human biopsies especially for target identification and the evaluation of biomarkers. Therefore, it is underlined that adequate anonymization must accompany the use of such data for protecting the personal rights, especially the genetic data of the study subjects. It is emphasized further to limit the size of a human biopsy to the minimal amount needed, which can be achieved only if the cooperating scientists develop and apply analytical methods with the highest sensitivity.

The management of multi-professional teams becomes an increasingly important problem in many social, industrial, and scientific activities. Several shared values are suggested to be essential for good and sustainable teamwork; inter alia, ethics, trust, and a clear definition of joint purpose. The profound knowledge of the scientific interest, personal integrity, ethical values, emotions, and cultural background of each participant helps communication and the sharing of knowledge and experience that all lead eventually to the efficient management of possible conflicts arising during joint work [24, 25]. These issues are covered in the section of Impartiality. The special distribution of competencies between participants of clinical trial teams is carefully defined stating that non-medically qualified members should not influence either the patients or the public “with scientific results without embedding these results into appropriate medical context.” Neither should scientists give advice to patients; this should be the exclusive right of the treating physician. Further moral advice for managing cooperation is given in the section dealing with Accountability in the Workplace. The authors emphasized that lifestyle, culture, beliefs, color, gender, and age should not influence professional relationships within the team. Furthermore, the great help of open discussion for joint decision making within the group is underlined. It must be ensured that all members understand both their joint and personal responsibilities for the scientific validity of the common research project and the safety of the patients.

The list of the different specialists participating in human trials of modern complex medicines is long, chemists, pharmacists, molecular biologists, geneticists, immunologists, device engineers, and many others as needed. Consequently, it will be more cumbersome to reach a consensus. Although both the physicians and the various scientists must receive ethical training before joining a multi-professional clinical research team, they might have differing moral views in specific situations. Indeed, Page demonstrated that in specific model circumstances, participants weighted the importance of the respect to autonomy, beneficence, non-maleficence, and justice differently. Moreover, the same individuals prioritized different values according to the specific situations [26]. Similarly, Ebbesen and Pedersen [27] found that scientists conducting animal experiments in a company developing anticancer agents valued these ethical norms markedly differently from physicians working on cancer wards. It seems that the prioritization of the ethical norms of Beauchamp and Childress and the overall ethical decision made by individuals is quite situation dependent. This is the reason why the importance of open and honest dialogs, the respect of personal integrity, and the special expertise of all group members are so emphatically recommended in the Ethical Framework.