Eur J ClinPharmacol(1991) 41:387-391
QeGcOH@@ © Springer-Verlag 199l
Special article The pharmaceutical physician - requirements for the position R. Schmidt ClinicalResearchDepartment SandozPharmaLtd., Basel, Switzerland Received:December 8, 1990/Acceptedin revisedform:February4, 1991
Summary. Physicians looking for a position as pharmaceutical physician are usually uncertain whether they are suitable for this activity by training and personal abilities. The main requirements are a major interest in therapeutics and research as well as the ability to treat a disease as an entity instead of the individual patient. The pharmaceutical physician is a specialist in the area of drug development. Even by treating populations and diseases his ultimate goal is to contribute to better care for the individual patient. Requirements for training and the personal abilities necessary for the position of a pharmaceutical physician are described and recommendations given for applicants.
Key words: Pharmaceutical physician; training, clinical trials, general requirements
Pharmaceutical medicine has become an established speciality of the medical profession. In England a diploma in the subject [1, 2] has existed for many years, and in 1989 a faculty of Pharmaceutical Medicine was established at the Royal College of Physicians. Until recently, the pharmaceutical physician was sometimes unjustly considered to be a minor version of a physician [3] because he does not perform several classical activities of the latter. In fact, he does - not treat individual patients - not work at the bedside - not make diagnoses - not work in an "independent" private practice but in a company with a hierarchical structure. The number of medically qualified collaborators in the clinical research department of a pharmaceutical company has increased manyfold in the past 20 years. More and more young physicians take into consideration a position in the pharmaceutical industry, which represents a real alternative to a clinical career. During the medical studies, however, no or only little information is given about pharmaceutical medicine. Physicians entering the
clinical research department of a company are faced, therefore, with a completely new field: drug development in general and its clinical part in particular. Previously the medical profession was represented in pharmaceutical companies by - pharmacologists - toxicologists and - medical advisers. The activity of the latter covered a broad spectrum [4, 5] from performing trials during clinical drug development up to advising doctors on registered products. The new title "pharmaceutical physician" evolved because the increasing scientific requirements in cfinical drug development required a clear separation from the former medical adviser. Today, a medical adviser cares for the more promotional contacts with physicians in clinics and private practice, whilst the pharmaceutical physician is responsible for scientific drug development. When the Associations of Medical Advisers in the Pharmaceutical Industry (AMAPI) of different countries established a global cooperation in 1975, they called the new organization "International Federation of Associations of Pharmaceutical Physicians" (IFAPP) [6]. The goal of the present essay is to provide information to young physicians on the requirements for the position of a pharmaceutical physician in the clinical research department of a pharmaceutical company, i.e. on the training and personal abilities required for this speciality. In the following the male pronoun "he" is used for simplicity, but it must be understood that the opportunities for the pharmaceutical physician are equal both for male and female candidates.
Training and abilities To feel satisfied in the position of a pharmaceutical physician the candidate should have the following main concerns: - A primary interest in therapeutics
388 - The wish to contribute to scientific and therapeutic progress - The desire to treat a disease as an entity instead of the individual patient - The readiness to renounce direct patient care. In addition, the following training should have been obtained:
Medical studies The pharmaceutical physician needs to have completed his studies and graduated in medicine. During those studies he must have been informed of the ethical principles of medical research and the conduct of a clinical trial, as described in the Declarations of Helsinki and Tokyo, established by the International Association of Physicians in 1965 and 1974 [7]. In addition, he should be familiar with the oath of Hippocrates.
Training in biological sciences Postgraduate training and experience in pathology, pharmacology, biochemistry, physiology or clinical pharmacology are an advantage but not an absolute necessity. If available, they will help the newcomer to become familiar more readily with the purely scientific part of the profession of the pharmaceutical physician, and to understand more easily, for instance, the mechanisms of action of new drugs. Special training in biological sciences, together with subsequent clinical experience, will also be helpful in drawing rational conclusions about clinical implications from the preclinical data on a new substance.
Clinical training and experience Postgraduate clinical experience is important in many ways in pharmaceutical medicine. It will teach the young physician what is meant by the expression the "clinical relevance" of the results of clinical trials. An inexperienced physician may be tempted to rely too much on "statistical significance", which in many cases is not identical with clinical relevance. During clinical training, it should also become apparent where therapeutic gaps exist that need to be filled. Further, clinical experience helps in precise definition of the criteria for patient selection, as well as of disease and disease stages in trial protocols. In this respect the pharmaceutical physician must also be experienced in clinical diagnosis. Finally, clinical training will contribute to realistic design of trials in the clinic, as only personal experience in hospitals or with out-patients will permit appreciation of the practicability of a clinical trial both for the participating patients as well as for the medical and nursing staff on the ward. Some companies offer their clinically well-trained pharmaceutical physicians the possibility of further parttime work in a clinical setting to maintain their familiarity with practical medicine, or to continue previous scientific work in the clinic. Others operate their own units of clini-
R. Schmidt: Requirements for the pharmaceutical physician cal pharmacology, where pharmaceutical physicians perform clinical studies [8, 9]. Special areas in pharmaceutical medicine Postgraduate practical experience in clinical medicine, and possibly a special training in the biological sciences, will enable a physician to cope with the many tasks and problems of the special are as of pharmaceutical medicine. In particular he should become familiar with the following topics:
Selection of trial design The pharmaceutical physician is expected to be familiar with the clinical trials methodology, especially the different types of clinical trials, and, in particular, the randomized clinical trial. It is of the utmost importance to select for each study an appropriate design (case control, parallel group, cross over, etc.) in order to make the final results as valid as possible, whilst keeping the number of patients exposed to the new drug as small as possible.
Performance of clinical trials Clinical drug development is divided into three phases. Each has its own goals and includes a number of the essentials required for final registration of the drug. Phase I represents investigation of the tolerability and kinetics and Phase II study of the efficacy and superiority of the new drug compared to established medicines. In Phase III large-scale and long-term studies are performed worldwide. The goal of all the activities is to define the efficacy and safety of a new drug, and to enable its so-called profiling, i.e. elaboration of the product characteristics and claims for the new drug, and positioning, namely the identification of the distinctive place for the new drug in relation to competitive products. Phase IV, after registration, comprises post-marketing surveillance and the development of new indications or new galenical formulations. In all the phases the pharmaceutical physician has to take over many responsibilities for the competent and appropriate conduct of the trials in healthy or diseased volunteers. He has to ensure that trials are conducted according to internationally accepted rules of ethics, he must also ensure that they progress according to the planned time table, and he may also have to coordinate activities in several hospitals in different countries. This means that he must not only be familiar with the international guidelines for clinical drug development but also represent a competent and active partner for the investigator in the clinic. The performance of clinical trials requires organizational talent.
Interpretation of preclinical data An experienced pharmaceutical physician has learned to understand and appreciate the preclinical data obtained from pharmacological, toxicological and biopharmaceuti-
R. Schmidt: Requirements for the pharmaceutical physician cal investigations, which indicate the pharmacodynamic properties and possible toxicological hazards of the new drug in man. When a new substance passes from animal to man, i.e. from preclinical development to clinical Phase I, not only does the trial design have to be defined, but also the first dose in man. The pharmaceutical physician must know how to estimate from the available preclinical results the first dose to be given to humans. Of course, he need not have the specialised competence of pharmacologists and toxicologists in their fields, but he must be able to understand and interpret their data and statements, and in a joint discussion to determine the first and further doses to be administered in man. The critical phase of transition of a drug from animal to man illustrates clearly that the pharmaceutical physician has a major responsibility during drug development.
Biostatistics The pharmaceutical physician must not only be informed about the design of clinical trials but he must also know how to evaluate them from a statistical point of view. He will usually rely on the assistance of an experienced statistician, but he must be able to discuss trial plans and results with him. The pharmaceutical physician is particularly important in clinical interpretation of statistical results. He has to translate statistics into clinical reality, i. e. he has to define when statistical significance means clinical relevance, and he must be aware when statistical non-significant results are nevertheless clinically relevant.
389 of interpreting the results not only from the purely quantitative point of view, but also in respect of their relevance and correlation with pharmacodynamic effects. He must ensure that the ultimate goal of pharmacokinetics, namely the correlation of drug level and drug response, is not neglected.
Marketing aspects A pharmaceutical company is a private enterprise and will not receive any external financial support. Products resulting from research must therefore pay back the cost of their development. The goal is to create by scientific methods a new marketable drug. A physician entering a pharmaceutical company must be aware that this will be also the ultimate goal of his personal work. He has to advise his colleagues from the marketing department on the properties of new compounds, their advantages over existing drugs and their possible drawbacks. The marketing process by its nature tends to broaden the use of a new drug as far as possible, and is directed to the appropriate competitive field, whilst the pharmaceutical physician is primarily focused on specific patient populations. These two seemingly opposed trends are in fact complementary and nevertheless most creative and stimulating, leading to new ideas for marketed drugs, as well as for the further development of new substances. However, it is essential that both partners from research and marketing have the ability to discuss their views of possible therapeutic applications in an objective manner.
Communication Therapeutic drug monitoring Tolerability and safety are closely monitored in all developmental phases of a new drug, as well as after registration. Special departments in research-based companies are responsible for the performance and evaluation of drug monitoring studies during drug development, and during the post-marketing surveillance period. It is not just the mere collection and listing of adverse drug events that is the essential part of the activity of the pharmaceutical physician in this respect, but rather the very important interpretation and appreciation of their clinical relevance and further implications for the drug, e.g. more precise definition of indications, requirement of safety precautions to be added to the package insert, etc.
Pharmacokinetics Usually specialists are involved in the planning of pharmacokinetic studies, but in many instances the pharmaceutical physician has to take over the clinical phase. He must be in a position to assist in the planning and performance of such studies. In addition, he has to contribute to interpretation of results. When non-medical colleagues are involved in the evaluation of pharmacokinetic studies, the pharmaceutical physician has the most important task
The pharmaceutical physician has many contacts within a company [10]. Final conclusions, proposals and decisions usually result from joint discussions in teams with colleagues from his own as well as from other departments involved in drug development. The pharmaceutical physician is, therefore, in frequent contact, especially with colleagues from the medical-biological sciences (pharmacology, toxicology, drug metabolism), as well as from the galenical department. He must be able to communicate with all these colleagues not only individually but also in a cooperative way within a team. In addition, he should have the ability to present results verbally and in writing to his colleagues as well as to the research management. Outside the company, the pharmaceutical physician has to deal with clinical investigators, consultants, authorities, and ethics committees, with whom he must comment on the pros and cons of each new development. He should also be able to present his research results at congresses and participate in publications.
Documentation As with any scientific study, the results of clinical trials have to be carefully recorded and documented. A poorly documented trial is not only unscientific but also unethi-
390 cal, and does not serve any useful purpose, particularly not with regard to the registration of a new drug. The pharmaceutical physician is assisted by project assistants or clinical research assistants, who help to collect and tabulate results, but the final responsibility for correctness lies with him and the clinical investigator in the clinic. Without needing to be a mathematician, the pharmaceutical physician must have some ability to cope with figures and calculations. He should also be aware of the potential and limits on the use of electronic data processing systems for handling and analysing information.
R. Schmidt: Requirements for the pharmaceutical physician trials in different areas of medicine and will ensure regular communication between company and trial centres after the trial protocol has been finalized between the investigator in the clinic and the medical expert in the company [11]. The medical expert is usually a specialist in one of the clinical disciplines (e. g. cardiology, endocrinology, psychiatry). The physician in a drug monitoring centre needs broad clinical training, whilst a monitor usually has more limited clinical training, both being generalists from the point of view of medicine.
Recommendations Cost awareness
The expenses of clinical trials have increased tremendously during in the past few years, due to the increase of costs in health care in general, the demands of authorities for extensive documentation of the safety and efficacy of a new drug, and the increasing competition between companies. The pharmaceutical physician must be able to work within a budget allocated to him and his project. He must be able to negotiate adequate reimbursement for a study with a clinical investigator. The final sum must be justifiable to the research management of the company as well as to governments and the public.
Before joining a company an applicant should be able to answer the following questions: Do I have - a major interest in rational drug therapy and therapeutic progress - an interest in performing research - the ability to participate in research with the ultimate goal of developing a marketable drug - the ability to • practice medicine as a science • give up direct care of patients • work within a multi-disciplinary team • work in a company with a hierarchical structure • be satisfied with a desk job.
Tutoring
Today, there are many books and courses on drug development and the principles of clinical pharmacology. They usually give an overview in selected chapters, but they never include the entirety of pharmaceutical medicine. A great deal of the latter has to be learned by day-to-day practice and it is essential that the junior has a senior colleague who is prepared to transmit his knowledge to him. Therefore, tutoring of young colleagues is an essential part of the activity of an experienced pharmaceutical physician. The introductory phase depends on the training and experience of the junior. It usually lasts for at least one year but can easily extend to two or three years in order to ensure full experience in all the areas.
Positions in clinical research departments The range of activities listed above is familiar to every pharmaceutical physician. Depending on his individual situation and position in a company one or other aspect is likely to be predominant. It is clear that a specialist in a drug monitoring department, or in a department of immunology, will have his main competence and activity in the appropriate field. A company which hires a physician with a long clinical training and specialization in immunology must wish to profit from this experience. Such a candidate will usually work as a medical expert in a department of clinical immunology, designing and evaluating clinical trials in this field. A candidate with more limited clinical experience is suitable as a study monitor. He will perform
When applying for a position in the pharmaceutical industry a physician should be able to answer these questions positively. Of course, whether those answers remain true over time will become evident only after experience in a company. It is important to obtain as much information as possible during discussions with colleagues working in the company about the special conditions and the special situation of the position applied for. A physician should not join a pharmaceutical company if his main goal is to work within "normal" office hours, to escape clinical responsibility, or to attain a high income. The tight time schedule of research projects today demands the full commitment of the pharmaceutical physician. Clinical responsibility is inherent in the tasks mentioned above. Salaries are usually appropriate and depend on training and competence. Promotion, even to top management, is open to all pharmaceutical physicians, although only a very small number with outstanding managerial skills reach the height of becoming an executive officer of a company. For physicians working in the clinical department of a pharmaceutical company, it is most gratifying to be actively involved with colleagues from the medical and biological sciences in the development of new drugs and new therapeutic principles. They are deeply interested in therapeutic research and therapeutic progress and in acquiring further grounding in science. They enjoy the many contacts with other researchers within their company and with reputable clinicians outside. They realize that even though they do not perform direct patient care at the bedside, the ultimate goal of pharmaceutical medicine lies with the patient.
391
R. Schmidt: Requirements for the pharmaceutical physician References: 1. Marsh BT, Luscombe DK (1981) A diploma course in pharmaceutical medicine. Proceedings of the IVth International Congress of Pharmaceutical Physicians. Pergamon, Paris, p 229 2. Macleod HM, Goldberg A (1981) Diploma in pharmaceutical medicine. Br J Clin Pharmaco112: 3-4 3. Berde B (1985) Physicians as employees of the pharmaceutical industry. Eur J Clin PharmacoI 28:363-365 4. Cromie BW (1973) Role of the medical adviser. In: Jouhar AJ, Grayson MF, (eds) International aspects of drug evaluation and usage. International Meeting of Medical Advisers in the Pharmaceutical Industry, London, April, 1972. Churchill Livingstone, Edinburgh, pp 171-176 5. Binns TB (1979) The role of the medical adviser in the past. In: MacLeod N, (ed) Pharmaceutical Medicine. Churchill Livingstone, Edinburgh pp 1-9 6. Lucchelli PE, Bergamini N, Bachini V (1976) Preface in: Rationality of drug development. Proceedings of the Second International Meeting of Medical Advisers in the Pharmaceutical Industry, Florence; October 13-15, 1975. Excerpta Medica, Amsterdam-Oxford; American Elsevier, New York
7. Declaration of Helsinki Recommendations guiding doctors in clinical research (1975). Fed Reg 40:16056 8. Ferguson RK, Vlasses PH, Abrams WB (1985) Academic-Industrial Clinical Pharmacology: A Working Model. J Clin Pharmacol 25:4-7 9. Schmidt R (1987) Klinische Pharmakologie in der Pharmaindustile - MOglichkeiten und Grenzen. In: Magometschnigg D (ed) Therapieversuch am Menschen. Uhlen, Wien 10. Nicolis FB (1978) The challenging role of the pharmaceutical physician - interactions with other disciplines in industry as viewed by the pharmaceutical physician. In: Pharmaceutical Medicine - The Future - Brussels, October 4-6, pp 418-429 ll. Schmidt R (1985) The responsibility for the study protocol in a drug trial. Int J Clin Pharmacol Ther Toxico123:158-160
Dr. R. Schmidt Clinical Research Department Sandoz Pharma Ltd. CH-4002 Basel Switzerland
QeGcOH@@ © Springer-Verlag 199l
Special article The pharmaceutical physician - requirements for the position R. Schmidt ClinicalResearchDepartment SandozPharmaLtd., Basel, Switzerland Received:December 8, 1990/Acceptedin revisedform:February4, 1991
Summary. Physicians looking for a position as pharmaceutical physician are usually uncertain whether they are suitable for this activity by training and personal abilities. The main requirements are a major interest in therapeutics and research as well as the ability to treat a disease as an entity instead of the individual patient. The pharmaceutical physician is a specialist in the area of drug development. Even by treating populations and diseases his ultimate goal is to contribute to better care for the individual patient. Requirements for training and the personal abilities necessary for the position of a pharmaceutical physician are described and recommendations given for applicants.
Key words: Pharmaceutical physician; training, clinical trials, general requirements
Pharmaceutical medicine has become an established speciality of the medical profession. In England a diploma in the subject [1, 2] has existed for many years, and in 1989 a faculty of Pharmaceutical Medicine was established at the Royal College of Physicians. Until recently, the pharmaceutical physician was sometimes unjustly considered to be a minor version of a physician [3] because he does not perform several classical activities of the latter. In fact, he does - not treat individual patients - not work at the bedside - not make diagnoses - not work in an "independent" private practice but in a company with a hierarchical structure. The number of medically qualified collaborators in the clinical research department of a pharmaceutical company has increased manyfold in the past 20 years. More and more young physicians take into consideration a position in the pharmaceutical industry, which represents a real alternative to a clinical career. During the medical studies, however, no or only little information is given about pharmaceutical medicine. Physicians entering the
clinical research department of a company are faced, therefore, with a completely new field: drug development in general and its clinical part in particular. Previously the medical profession was represented in pharmaceutical companies by - pharmacologists - toxicologists and - medical advisers. The activity of the latter covered a broad spectrum [4, 5] from performing trials during clinical drug development up to advising doctors on registered products. The new title "pharmaceutical physician" evolved because the increasing scientific requirements in cfinical drug development required a clear separation from the former medical adviser. Today, a medical adviser cares for the more promotional contacts with physicians in clinics and private practice, whilst the pharmaceutical physician is responsible for scientific drug development. When the Associations of Medical Advisers in the Pharmaceutical Industry (AMAPI) of different countries established a global cooperation in 1975, they called the new organization "International Federation of Associations of Pharmaceutical Physicians" (IFAPP) [6]. The goal of the present essay is to provide information to young physicians on the requirements for the position of a pharmaceutical physician in the clinical research department of a pharmaceutical company, i.e. on the training and personal abilities required for this speciality. In the following the male pronoun "he" is used for simplicity, but it must be understood that the opportunities for the pharmaceutical physician are equal both for male and female candidates.
Training and abilities To feel satisfied in the position of a pharmaceutical physician the candidate should have the following main concerns: - A primary interest in therapeutics
388 - The wish to contribute to scientific and therapeutic progress - The desire to treat a disease as an entity instead of the individual patient - The readiness to renounce direct patient care. In addition, the following training should have been obtained:
Medical studies The pharmaceutical physician needs to have completed his studies and graduated in medicine. During those studies he must have been informed of the ethical principles of medical research and the conduct of a clinical trial, as described in the Declarations of Helsinki and Tokyo, established by the International Association of Physicians in 1965 and 1974 [7]. In addition, he should be familiar with the oath of Hippocrates.
Training in biological sciences Postgraduate training and experience in pathology, pharmacology, biochemistry, physiology or clinical pharmacology are an advantage but not an absolute necessity. If available, they will help the newcomer to become familiar more readily with the purely scientific part of the profession of the pharmaceutical physician, and to understand more easily, for instance, the mechanisms of action of new drugs. Special training in biological sciences, together with subsequent clinical experience, will also be helpful in drawing rational conclusions about clinical implications from the preclinical data on a new substance.
Clinical training and experience Postgraduate clinical experience is important in many ways in pharmaceutical medicine. It will teach the young physician what is meant by the expression the "clinical relevance" of the results of clinical trials. An inexperienced physician may be tempted to rely too much on "statistical significance", which in many cases is not identical with clinical relevance. During clinical training, it should also become apparent where therapeutic gaps exist that need to be filled. Further, clinical experience helps in precise definition of the criteria for patient selection, as well as of disease and disease stages in trial protocols. In this respect the pharmaceutical physician must also be experienced in clinical diagnosis. Finally, clinical training will contribute to realistic design of trials in the clinic, as only personal experience in hospitals or with out-patients will permit appreciation of the practicability of a clinical trial both for the participating patients as well as for the medical and nursing staff on the ward. Some companies offer their clinically well-trained pharmaceutical physicians the possibility of further parttime work in a clinical setting to maintain their familiarity with practical medicine, or to continue previous scientific work in the clinic. Others operate their own units of clini-
R. Schmidt: Requirements for the pharmaceutical physician cal pharmacology, where pharmaceutical physicians perform clinical studies [8, 9]. Special areas in pharmaceutical medicine Postgraduate practical experience in clinical medicine, and possibly a special training in the biological sciences, will enable a physician to cope with the many tasks and problems of the special are as of pharmaceutical medicine. In particular he should become familiar with the following topics:
Selection of trial design The pharmaceutical physician is expected to be familiar with the clinical trials methodology, especially the different types of clinical trials, and, in particular, the randomized clinical trial. It is of the utmost importance to select for each study an appropriate design (case control, parallel group, cross over, etc.) in order to make the final results as valid as possible, whilst keeping the number of patients exposed to the new drug as small as possible.
Performance of clinical trials Clinical drug development is divided into three phases. Each has its own goals and includes a number of the essentials required for final registration of the drug. Phase I represents investigation of the tolerability and kinetics and Phase II study of the efficacy and superiority of the new drug compared to established medicines. In Phase III large-scale and long-term studies are performed worldwide. The goal of all the activities is to define the efficacy and safety of a new drug, and to enable its so-called profiling, i.e. elaboration of the product characteristics and claims for the new drug, and positioning, namely the identification of the distinctive place for the new drug in relation to competitive products. Phase IV, after registration, comprises post-marketing surveillance and the development of new indications or new galenical formulations. In all the phases the pharmaceutical physician has to take over many responsibilities for the competent and appropriate conduct of the trials in healthy or diseased volunteers. He has to ensure that trials are conducted according to internationally accepted rules of ethics, he must also ensure that they progress according to the planned time table, and he may also have to coordinate activities in several hospitals in different countries. This means that he must not only be familiar with the international guidelines for clinical drug development but also represent a competent and active partner for the investigator in the clinic. The performance of clinical trials requires organizational talent.
Interpretation of preclinical data An experienced pharmaceutical physician has learned to understand and appreciate the preclinical data obtained from pharmacological, toxicological and biopharmaceuti-
R. Schmidt: Requirements for the pharmaceutical physician cal investigations, which indicate the pharmacodynamic properties and possible toxicological hazards of the new drug in man. When a new substance passes from animal to man, i.e. from preclinical development to clinical Phase I, not only does the trial design have to be defined, but also the first dose in man. The pharmaceutical physician must know how to estimate from the available preclinical results the first dose to be given to humans. Of course, he need not have the specialised competence of pharmacologists and toxicologists in their fields, but he must be able to understand and interpret their data and statements, and in a joint discussion to determine the first and further doses to be administered in man. The critical phase of transition of a drug from animal to man illustrates clearly that the pharmaceutical physician has a major responsibility during drug development.
Biostatistics The pharmaceutical physician must not only be informed about the design of clinical trials but he must also know how to evaluate them from a statistical point of view. He will usually rely on the assistance of an experienced statistician, but he must be able to discuss trial plans and results with him. The pharmaceutical physician is particularly important in clinical interpretation of statistical results. He has to translate statistics into clinical reality, i. e. he has to define when statistical significance means clinical relevance, and he must be aware when statistical non-significant results are nevertheless clinically relevant.
389 of interpreting the results not only from the purely quantitative point of view, but also in respect of their relevance and correlation with pharmacodynamic effects. He must ensure that the ultimate goal of pharmacokinetics, namely the correlation of drug level and drug response, is not neglected.
Marketing aspects A pharmaceutical company is a private enterprise and will not receive any external financial support. Products resulting from research must therefore pay back the cost of their development. The goal is to create by scientific methods a new marketable drug. A physician entering a pharmaceutical company must be aware that this will be also the ultimate goal of his personal work. He has to advise his colleagues from the marketing department on the properties of new compounds, their advantages over existing drugs and their possible drawbacks. The marketing process by its nature tends to broaden the use of a new drug as far as possible, and is directed to the appropriate competitive field, whilst the pharmaceutical physician is primarily focused on specific patient populations. These two seemingly opposed trends are in fact complementary and nevertheless most creative and stimulating, leading to new ideas for marketed drugs, as well as for the further development of new substances. However, it is essential that both partners from research and marketing have the ability to discuss their views of possible therapeutic applications in an objective manner.
Communication Therapeutic drug monitoring Tolerability and safety are closely monitored in all developmental phases of a new drug, as well as after registration. Special departments in research-based companies are responsible for the performance and evaluation of drug monitoring studies during drug development, and during the post-marketing surveillance period. It is not just the mere collection and listing of adverse drug events that is the essential part of the activity of the pharmaceutical physician in this respect, but rather the very important interpretation and appreciation of their clinical relevance and further implications for the drug, e.g. more precise definition of indications, requirement of safety precautions to be added to the package insert, etc.
Pharmacokinetics Usually specialists are involved in the planning of pharmacokinetic studies, but in many instances the pharmaceutical physician has to take over the clinical phase. He must be in a position to assist in the planning and performance of such studies. In addition, he has to contribute to interpretation of results. When non-medical colleagues are involved in the evaluation of pharmacokinetic studies, the pharmaceutical physician has the most important task
The pharmaceutical physician has many contacts within a company [10]. Final conclusions, proposals and decisions usually result from joint discussions in teams with colleagues from his own as well as from other departments involved in drug development. The pharmaceutical physician is, therefore, in frequent contact, especially with colleagues from the medical-biological sciences (pharmacology, toxicology, drug metabolism), as well as from the galenical department. He must be able to communicate with all these colleagues not only individually but also in a cooperative way within a team. In addition, he should have the ability to present results verbally and in writing to his colleagues as well as to the research management. Outside the company, the pharmaceutical physician has to deal with clinical investigators, consultants, authorities, and ethics committees, with whom he must comment on the pros and cons of each new development. He should also be able to present his research results at congresses and participate in publications.
Documentation As with any scientific study, the results of clinical trials have to be carefully recorded and documented. A poorly documented trial is not only unscientific but also unethi-
390 cal, and does not serve any useful purpose, particularly not with regard to the registration of a new drug. The pharmaceutical physician is assisted by project assistants or clinical research assistants, who help to collect and tabulate results, but the final responsibility for correctness lies with him and the clinical investigator in the clinic. Without needing to be a mathematician, the pharmaceutical physician must have some ability to cope with figures and calculations. He should also be aware of the potential and limits on the use of electronic data processing systems for handling and analysing information.
R. Schmidt: Requirements for the pharmaceutical physician trials in different areas of medicine and will ensure regular communication between company and trial centres after the trial protocol has been finalized between the investigator in the clinic and the medical expert in the company [11]. The medical expert is usually a specialist in one of the clinical disciplines (e. g. cardiology, endocrinology, psychiatry). The physician in a drug monitoring centre needs broad clinical training, whilst a monitor usually has more limited clinical training, both being generalists from the point of view of medicine.
Recommendations Cost awareness
The expenses of clinical trials have increased tremendously during in the past few years, due to the increase of costs in health care in general, the demands of authorities for extensive documentation of the safety and efficacy of a new drug, and the increasing competition between companies. The pharmaceutical physician must be able to work within a budget allocated to him and his project. He must be able to negotiate adequate reimbursement for a study with a clinical investigator. The final sum must be justifiable to the research management of the company as well as to governments and the public.
Before joining a company an applicant should be able to answer the following questions: Do I have - a major interest in rational drug therapy and therapeutic progress - an interest in performing research - the ability to participate in research with the ultimate goal of developing a marketable drug - the ability to • practice medicine as a science • give up direct care of patients • work within a multi-disciplinary team • work in a company with a hierarchical structure • be satisfied with a desk job.
Tutoring
Today, there are many books and courses on drug development and the principles of clinical pharmacology. They usually give an overview in selected chapters, but they never include the entirety of pharmaceutical medicine. A great deal of the latter has to be learned by day-to-day practice and it is essential that the junior has a senior colleague who is prepared to transmit his knowledge to him. Therefore, tutoring of young colleagues is an essential part of the activity of an experienced pharmaceutical physician. The introductory phase depends on the training and experience of the junior. It usually lasts for at least one year but can easily extend to two or three years in order to ensure full experience in all the areas.
Positions in clinical research departments The range of activities listed above is familiar to every pharmaceutical physician. Depending on his individual situation and position in a company one or other aspect is likely to be predominant. It is clear that a specialist in a drug monitoring department, or in a department of immunology, will have his main competence and activity in the appropriate field. A company which hires a physician with a long clinical training and specialization in immunology must wish to profit from this experience. Such a candidate will usually work as a medical expert in a department of clinical immunology, designing and evaluating clinical trials in this field. A candidate with more limited clinical experience is suitable as a study monitor. He will perform
When applying for a position in the pharmaceutical industry a physician should be able to answer these questions positively. Of course, whether those answers remain true over time will become evident only after experience in a company. It is important to obtain as much information as possible during discussions with colleagues working in the company about the special conditions and the special situation of the position applied for. A physician should not join a pharmaceutical company if his main goal is to work within "normal" office hours, to escape clinical responsibility, or to attain a high income. The tight time schedule of research projects today demands the full commitment of the pharmaceutical physician. Clinical responsibility is inherent in the tasks mentioned above. Salaries are usually appropriate and depend on training and competence. Promotion, even to top management, is open to all pharmaceutical physicians, although only a very small number with outstanding managerial skills reach the height of becoming an executive officer of a company. For physicians working in the clinical department of a pharmaceutical company, it is most gratifying to be actively involved with colleagues from the medical and biological sciences in the development of new drugs and new therapeutic principles. They are deeply interested in therapeutic research and therapeutic progress and in acquiring further grounding in science. They enjoy the many contacts with other researchers within their company and with reputable clinicians outside. They realize that even though they do not perform direct patient care at the bedside, the ultimate goal of pharmaceutical medicine lies with the patient.
391
R. Schmidt: Requirements for the pharmaceutical physician References: 1. Marsh BT, Luscombe DK (1981) A diploma course in pharmaceutical medicine. Proceedings of the IVth International Congress of Pharmaceutical Physicians. Pergamon, Paris, p 229 2. Macleod HM, Goldberg A (1981) Diploma in pharmaceutical medicine. Br J Clin Pharmaco112: 3-4 3. Berde B (1985) Physicians as employees of the pharmaceutical industry. Eur J Clin PharmacoI 28:363-365 4. Cromie BW (1973) Role of the medical adviser. In: Jouhar AJ, Grayson MF, (eds) International aspects of drug evaluation and usage. International Meeting of Medical Advisers in the Pharmaceutical Industry, London, April, 1972. Churchill Livingstone, Edinburgh, pp 171-176 5. Binns TB (1979) The role of the medical adviser in the past. In: MacLeod N, (ed) Pharmaceutical Medicine. Churchill Livingstone, Edinburgh pp 1-9 6. Lucchelli PE, Bergamini N, Bachini V (1976) Preface in: Rationality of drug development. Proceedings of the Second International Meeting of Medical Advisers in the Pharmaceutical Industry, Florence; October 13-15, 1975. Excerpta Medica, Amsterdam-Oxford; American Elsevier, New York
7. Declaration of Helsinki Recommendations guiding doctors in clinical research (1975). Fed Reg 40:16056 8. Ferguson RK, Vlasses PH, Abrams WB (1985) Academic-Industrial Clinical Pharmacology: A Working Model. J Clin Pharmacol 25:4-7 9. Schmidt R (1987) Klinische Pharmakologie in der Pharmaindustile - MOglichkeiten und Grenzen. In: Magometschnigg D (ed) Therapieversuch am Menschen. Uhlen, Wien 10. Nicolis FB (1978) The challenging role of the pharmaceutical physician - interactions with other disciplines in industry as viewed by the pharmaceutical physician. In: Pharmaceutical Medicine - The Future - Brussels, October 4-6, pp 418-429 ll. Schmidt R (1985) The responsibility for the study protocol in a drug trial. Int J Clin Pharmacol Ther Toxico123:158-160
Dr. R. Schmidt Clinical Research Department Sandoz Pharma Ltd. CH-4002 Basel Switzerland
