816
A Question of Ethics IS IT ETHICAL TO CONDUCT VOLUNTEER STUDIES WITHIN THE PHARMACEUTICAL INDUSTRY?
J. K. BUTLER G. D. Searle &
There is a case for appropriately selected drug studies within the pharmaceutical industry in which employee volunteers are used. Provided the organisation and conduct of such studies are approached in an ethical manner, with attention to safeguarding the volunteer and recognising the limitations, this work can be done expeditiously, cheaply, and safely. Some details are given of the arrangements made for volunteer studies within a company. INTRODUCTION
drugs or new formulations
of existing drugs are for the advancement of medical science. Infornecessary mation on efficacy and acceptability can be acquired only from well-planned and well-conducted studies in patients, but information about the bioavailability, pharmacokinetics, and metabolism of drugs can often be gained from studies in normal volunteers. Such studies must be ethically and scientifically sound and they must be conducted by competent clinicians.
WHAT CONSTITUTES AN ETHICAL VOLUNTEER
STUDY?
There is no simple answer to what constitutes an ethical volunteer study. In a therapeutic trial involving patients, the potential benefits are balanced against the known risks and the possibilities of unknown risks. In volunteer studies, the risks may be less predictable and there are no health benefits. There may be other benefits such as financial, altruistic, or scientific ones but none of these can carry much weight in the equation of benefit-versus-risk. It therefore follows that the risks involved in volunteer studies must be negligible in terms of frequency or trivial in terms of
severity. The revised Declaration of Helsinki’ states that, "In the field of biomedical research a fundamental distinction must be recognised between medical research in which the aim is essentially diagnostic or therapeutic for a patient, and medical research, the essential object of which is purely scientific and without direct diagnostic or therapeutic value to the person subjected to the research" and that, "Concern for the interest of the subject must always prevail over the interests of science and
society". The final decisions and responsibility must lie with the investigator carrying out the study-no amount of informed consent, peer review, or insurance cover can take that responsibility away. The investigator must have both in-depth knowledge of his subject and total in-
tegrity.
merit.
IS IT ETHICAL TO PERFORM VOLUNTEER STUDIES WITHIN
Co. Ltd., PO Box 53, Lane End Road, High Wycombe, Bucks HP12 4HL
Summary
NEW
A volunteer study which cannot be expected to provide useful scientific data because of poor design or execution cannot be ethical since the risk of giving drugs to people can never be zero. The investigator must therefore submit a detailed protocol for an independent review from an ethical standpoint, including scientific
THE PHARMACEUTICAL
INDUSTRY?
Technical expertise within the drug company-A medical monitor responsible for a compound should have broad first-hand knowledge of all the preclinical data available, including the chemistry, animal pharmacology, and toxicology, and is in an ideal position to discuss these subjects with the appropriate specialists within the company. However much an outside investigator is provided with such data by discussion and by reading preclinical study reports, it is unlikely that he will become as familiar with the subject as an "in-house" monitor. The company is likely to have appropriate facilities for measuring the levels of the drug and its metabolites in blood and urine. Even if the existing analytical procedures are applicable only to quality control or animal studies (because, for instance, the limits of sensitivity are too high for the detection of amounts likely to be found in human biological fluids after small doses), these procedures may form a good basis for others which are more appropriate to early human studies. If studies are to be conducted outside the company, the clinical pharmacology unit concerned will need to set up analytical procedures itself or arrange for samples to be sent back to the company for analysis. Either way there may be delays and additional opportunities for human error. Continuous review of the study-A study conducted within the company allows the various groups to work closely-the clinician can and should feed information back to the relevant chemists, animal pharmacologists, toxicologists, and bioanalytical staff as studies proceed. This feedback is especially important in early tolerance and activity studies, and may reduce withdrawal symptoms amongst the preclinical scientists who, having worked extensively on a compound, may feel deprived if they are not kept informed of the follow-up.
Speed-If new drugs or improved formulations are useful, then expediting these advances must be relevant to ethical questions. It saves time to carry out studies within the company, because the company can set its own priorities, whereas the degree of priority which a study receives in a department of clinical pharmacology will depend more on the academic interest of the project than on its importance to the company. For example, a routine bioavailability study to investigate a proposed formulation change on a marketed compound may be delayed though the information is urgently needed by the company or a regulatory authority.
Accuracy of the data-The accuracy of the data may be greater in studies conducted by the clinical monitor in industry who has to meet stringent scrutiny by his scientific colleagues and government authorities and is to
detail, such
more
likely
to
pay close
atten-
precise timing of obtaining bloodsamples. Good laboratory practice requirements proposed by the Food and Drug Administration in the United States are being incorporated into clinical studies in industry but not into academic medical research in the United Kingdom. A study cannot be ethically justified if, through lack of attention to tion
as
the
detail, its results are not valid scientifically.
Liability-The company and anyone doing volunteer work in industry are vulnerable especially to accusations, informed or
817 must therefore be (and be seen to act) in an ethical fashespecially vigilant ion. This is conducive to high standards. As Laurence stated in 19642, "... it could be argued that the consequences of any on a drug firm unmishap will be visited with especial severity " clinical dertaking experimentation...
otherwise, of unethical behaviour and they to act
Calibre
of medical personnel-Although clinicians working in
industry may have been regarded by their hospital counterparts as less competent doctors, they are generally of a high calibre and "us-and-them" attitudes have largely disappeared. Drug development is now a specialised and demanding branch of medical science which requires, and has helped to create, a mutually respectful coexistence between medical personnel in industry and hospitals. The physician in industry benefits considerably from practical responsibility for studies, and learns more about the drugs involved and the practical realities of carrying out the study than if he were only to plan studies to be conducted elsewhere. on potential volunteers-One of the possible reasons why studies involving company employees may be unethical is that employees may be under pressure to volunteer. This should not be the case and there should be adequate safeguards against pressure, including carefully and honestly conducted informed-consent interviews. In reality, the risk of pressure on medical students or other groups in hospitals may be at least
Pressure
as
great.
Facilities available-The only real potential problem may be the lack of adequate facilities should an acute medical problem such as anaphylaxis or cardiac dysrhythmia occur. The standards of physical facilities and type of staff available vary between companies, which do not, however, normally have an experienced resuscitation team or the type of facilities found in an intensive-care unit. Companies should have appropriate drugs and resuscitation equipment available but complex equipment is pointless unless there are people trained in its use; a resuscitator hanging on the wall does not ensure safety.
There are therefore some limitations to what can be done within pharmaceutical companies but danger arises only if the limitations are not recognised and the type of study undertaken is too ambitious. With adequate staff and facilities, it should be perfectly in order to conduct ethically acceptable studies on the bioavailability, pharmacokinetics, and metabolism of compounds, especially since many of the studies will involve marketed compounds on which more detailed information is required or on which a formulation change is proposed. It should also be possible to do tolerance and activity studies on appropriately selected new compounds. Valuable information can be gained about the activity of diuretics, anticholinergics, &c. in normal volunteers before studying efficacy in disease.
HOW TO ENSURE THAT SUCH STUDIES ARE ETHICAL
Selection of Volunteers Most authorities recommend that volunteers should be recruited by open invitations (for example, on notice boards) rather than by direct approach. The system at G. D. Searle, where about 40 studies have been conducted over four years, falls between the two. All employees between the ages of 18 and 65 were asked if they were interested in principle in taking part in stu-
dies ; the purely voluntary, no-obligation nature of the invitation was emphasised. Those who replied positively
pool of potential volunteers who could be approached in rotation or as required by a particular study with respect to sex or age-group. When a volunteer takes part in a study, details are recorded on his card and this guards against over-volunteering. Because early pregnancy cannot be excluded by standard laboratory screening, women of child-bearing age have been included only in studies on compounds which have been formed
a
the market for several years. Volunteers are screened for fitness by history, physical examination, blood biochemistry, haematology, and urinalysis. Normal results are a prerequisite for taking part in a study and form a useful baseline against which to compare subsequent tests. We also write to the volunteer’s general practitioner, with the individual’s consent, giving brief details of the study and asking whether there is any reason why the subject should not take part. If problems, such as hypertension or proteinuria are found, the examination is repeated and the problem discussed with the individual’s general practitioner, the subject being informed of the abnormal finding only with the general practitioner’s approval. on
What Motivates Volunteers altruism and scientific interest play some in motivation, financial reward is the main factor part as demonstrated by Hassar et awl. Payment has generally been considered ethically justifiable by those people or committees who have reviewed the question and it is probably essential in practice. A committee set up by the Association of the British Pharmaceutical Industry recommends4 that the amount paid should be reasonably related to the effort and discomfort anticipated but both Stuart-Harriss and Tyrre116 warn against the dangers of excessive payments which may constitute a bribe. The distinction between a reasonable financial reward and a bribe is blurred but the aim should be a formula which ensures adequate payment, taking into consideration the duration of the study, the degree of discomfort (such as from venepunctures) and the degree of inconvenience (such as from dietary restrictions or collection of urine or stool samples).
Although
Informed Consent Informed consent is essential but how informed is it really? Williams7 has suggested that the informed-consent interview may be a ritual which deceives both subject and doctor when the subject is uneducated, and Hassar8 used the term "unirrformed consent" in a report of a study in which most subjects appeared to have misunderstood or forgotten the information they were given. Tyrre115 has pointed out that the information given is bound to be restricted and consent is bound to be personal. Nevertheless, the investigator should explain the purpose of the study carefully, discuss the possible risks, and describe the plan of the study, drawing attention to restrictions which have to be imposed and blood or other samples which will be required. We conduct the consent interview in the presence of a third person who witnesses the volunteer contract. Insurance All volunteers at G. D. Searle are insured with life of five times their annual salary and with illness
cover
818
appropriate to the degree of disability by means of personal accident and illness policy rather than by an extension of an Employers Liability or Public Liability Policy. This ensures that in the event of an illness or death, a claim would be met without question, whereas with an Employers Liability Policy, the insurance company may expect the injured party to prove the employer’s negligence. cover
Ethical Review
Protocols must be reviewed from a purely scientific standpoint. At Searle an international system reviews all protocols for their scientific merit. In addition, a local ethical committee reviews proposed in-house studies. Committee meetings are attended by the clinical monitors whose protocols are under review for them to answer technical questions. The frequently used term, "independent ethical
review", suggests that the committee members should be connected with or chosen by anyone connected with the volunteer studies. This ideal is difficult to achieve since it is important that the members should be suitable as well as independent. Our committee chairman is a senior consultant physician at the local hospital and the other members are a consultant haematologist, a group pharmacist, a schoolteacher with a chemistry degree, and a personnel manager. The committee members accept the responsibility and demands on their time without financial or other material reward. It could be argued that this committee is not truly independent since its membership was partly determined by Searle employees. It is however probably as independent as any appropriate and effective ethical committee can be and its degree of independence compares favourably with equivalent committees in hospitals. not
CONCLUSION
I believe that the arguments for and against conducting drug studies involving normal volunteers within a pharmaceutical company show that such studies can, and perhaps even should, be done, provided their organisation and conduct are approached in a scientific and ethical mariner and provided the limitations of carrying out studies in pharmaceutical companies are recognised. The following helped to make arrangements for planning and conducting volunteer studies at G. D. Searle & Co.: Dr M. J. Asbury, Dr J. M. Clarke, Mr I. R. Harrision, Mrs M. Porteous, Dr L. E. Ramsay (now at the Gardiner Institute of Medicine, Western Infirmary, Glasgow), Dr M. J. Tidd, and Dr G. R. Venning. I also thank the members of the Ethical Committee for their help. REFERENCES 1. Wld Hlth Org. Chron. 1976, 30, 360. 2. Laurence, D. R. in Evaluation of Drug Activities: Pharmacometrics (edited by D. R. Laurence and A. L. Bacharach); p.3. London and New York, 1964. 3. Hassar, M., Pocelinko, R., Weintraub, M., Nelson, D., Thomas, G., Lasagna L. Clin. Pharmac. Ther. 1977, 21, 515. 4. The Report of the Committee to Investigate Medical Experiments on Staff Volunteers. Association of the British Pharmaceutical Industry. London, 1970. 5. Stuart-Harris, C. in International Aspects of Drug Evaluation and Usage (edited by A. J. Jouhar and M. F. Grayson); p.205. Edinburgh and Lon-
don, 1973. 6. Tyrrell, D. A. J. ibid. p.211. 7. Br. med. J. 1973, ii, 220. 8. Hassar, M., Wemtraub, M. Clin. Pharmac. Ther.
1976, 20, 379.
In
England
THE ROYAL
Now
FREE’S 150TH
ANNIVERSARY
young surgeon returning home one December upon a destitute dying girl on the steps of St Andrew’s Church, Holborn. He was unable to secure her admission to hospital and the incident distressed him so much that he immediately enlisted the help of his friends to found a medical charity to provide accommodation for the sick poor regardless of their means and without the necessity of a governor’s letter of introduction. Such was the beginning of what IN 1828
night
a
came
is now a teaching hospital of international repute, The Royal Free. And on April 17, 1978, at St. Andrew’s Church, where it all began, the hospital celebrates its 150 years of existence with a Thanksgiving Service in the presence of its Patron, Princess Alice, Duchess of Gloucester; and it will also honour the memory of the young surgeon, William Marsden. The Lancet is particularly pleased to add its congratulations, for Thomas Wakley, founder of the journal, and Marsden were contemporaries with similar ideals and humanitarian principles ; and Wakley’s son was later to be on the consultant surgical staff of the hospital and also chairman of the management committee. The hospital was first opened in Hatton Garden. There is no record of the number of beds, but it seems probable that only the homeless or the dying were actually taken into the wards and that the majority who came to the hospital were treated as outpatients. But such were the idealistic yet practical principles at its heart that in 1832 when all other hospitals refused to admit patients suffering from cholera, 700 cases were treated at The Free Hospital. In 1842 when premises formerly used as the barracks of the Light Horse Volunteers in Gray’s Inn Road fell vacant the committee of management bought the lease and in 1863 the freehold was purchased. This was the parent hospital until a few years ago; although all the original buildings were rebuilt and others added, the barrack structure of the hospital was plainly recognisable. Queen Victoria was Patron of the hospital on her accession to the throne and granted a Royal Charter in 1892, so the full derivation of its name emerges. Medical and social history was made in 1874. A small band of women, led by Sophia Jex-Blake and Elizabeth Garrett Anderson, were determined to found a medical school for women, for the Apothecaries’ Society had altered its rules to prevent women qualifying as doctors and no university would admit them; thus, the London School of Medicine for Women was founded. The pioneers were reduced almost to despair when they found that no hospital would admit women students and, unless the school was able to provide clinical instructions for its students, it was doomed. Once more the hospital gave the lead to medical and public opinion by opening its wards to women students, thereby securing the entry of women into the medical profession. In 1947 the school became coeducational by revision of its charter. As time progressed, additional hospitals became associated with Gray’s Inn Road to form the Royal Free Group. In 1974, the 850-bed new Royal Free District General and Teaching Hospital opened in Hampstead, a triumph of planning and cooperation, for the new building was actually built and commissioned while the nearby Lawn Road branch was in full use. Another event this year will be the opening of the clinical sciences building and the School of Medicine, making up the total complex of the Hospital. None can have a more favourable prospect for any aspect of service to the community, and the local population are fortunate, despite its size, in having the Free in its midst. During 1978 there will be many celebrations, some highly original (the Art Gallery exhibitions are already widely acclaimed); and the 3000 staff and 300 undergraduate students who work there each day have every right to take pride in their history and their future.
A Question of Ethics IS IT ETHICAL TO CONDUCT VOLUNTEER STUDIES WITHIN THE PHARMACEUTICAL INDUSTRY?
J. K. BUTLER G. D. Searle &
There is a case for appropriately selected drug studies within the pharmaceutical industry in which employee volunteers are used. Provided the organisation and conduct of such studies are approached in an ethical manner, with attention to safeguarding the volunteer and recognising the limitations, this work can be done expeditiously, cheaply, and safely. Some details are given of the arrangements made for volunteer studies within a company. INTRODUCTION
drugs or new formulations
of existing drugs are for the advancement of medical science. Infornecessary mation on efficacy and acceptability can be acquired only from well-planned and well-conducted studies in patients, but information about the bioavailability, pharmacokinetics, and metabolism of drugs can often be gained from studies in normal volunteers. Such studies must be ethically and scientifically sound and they must be conducted by competent clinicians.
WHAT CONSTITUTES AN ETHICAL VOLUNTEER
STUDY?
There is no simple answer to what constitutes an ethical volunteer study. In a therapeutic trial involving patients, the potential benefits are balanced against the known risks and the possibilities of unknown risks. In volunteer studies, the risks may be less predictable and there are no health benefits. There may be other benefits such as financial, altruistic, or scientific ones but none of these can carry much weight in the equation of benefit-versus-risk. It therefore follows that the risks involved in volunteer studies must be negligible in terms of frequency or trivial in terms of
severity. The revised Declaration of Helsinki’ states that, "In the field of biomedical research a fundamental distinction must be recognised between medical research in which the aim is essentially diagnostic or therapeutic for a patient, and medical research, the essential object of which is purely scientific and without direct diagnostic or therapeutic value to the person subjected to the research" and that, "Concern for the interest of the subject must always prevail over the interests of science and
society". The final decisions and responsibility must lie with the investigator carrying out the study-no amount of informed consent, peer review, or insurance cover can take that responsibility away. The investigator must have both in-depth knowledge of his subject and total in-
tegrity.
merit.
IS IT ETHICAL TO PERFORM VOLUNTEER STUDIES WITHIN
Co. Ltd., PO Box 53, Lane End Road, High Wycombe, Bucks HP12 4HL
Summary
NEW
A volunteer study which cannot be expected to provide useful scientific data because of poor design or execution cannot be ethical since the risk of giving drugs to people can never be zero. The investigator must therefore submit a detailed protocol for an independent review from an ethical standpoint, including scientific
THE PHARMACEUTICAL
INDUSTRY?
Technical expertise within the drug company-A medical monitor responsible for a compound should have broad first-hand knowledge of all the preclinical data available, including the chemistry, animal pharmacology, and toxicology, and is in an ideal position to discuss these subjects with the appropriate specialists within the company. However much an outside investigator is provided with such data by discussion and by reading preclinical study reports, it is unlikely that he will become as familiar with the subject as an "in-house" monitor. The company is likely to have appropriate facilities for measuring the levels of the drug and its metabolites in blood and urine. Even if the existing analytical procedures are applicable only to quality control or animal studies (because, for instance, the limits of sensitivity are too high for the detection of amounts likely to be found in human biological fluids after small doses), these procedures may form a good basis for others which are more appropriate to early human studies. If studies are to be conducted outside the company, the clinical pharmacology unit concerned will need to set up analytical procedures itself or arrange for samples to be sent back to the company for analysis. Either way there may be delays and additional opportunities for human error. Continuous review of the study-A study conducted within the company allows the various groups to work closely-the clinician can and should feed information back to the relevant chemists, animal pharmacologists, toxicologists, and bioanalytical staff as studies proceed. This feedback is especially important in early tolerance and activity studies, and may reduce withdrawal symptoms amongst the preclinical scientists who, having worked extensively on a compound, may feel deprived if they are not kept informed of the follow-up.
Speed-If new drugs or improved formulations are useful, then expediting these advances must be relevant to ethical questions. It saves time to carry out studies within the company, because the company can set its own priorities, whereas the degree of priority which a study receives in a department of clinical pharmacology will depend more on the academic interest of the project than on its importance to the company. For example, a routine bioavailability study to investigate a proposed formulation change on a marketed compound may be delayed though the information is urgently needed by the company or a regulatory authority.
Accuracy of the data-The accuracy of the data may be greater in studies conducted by the clinical monitor in industry who has to meet stringent scrutiny by his scientific colleagues and government authorities and is to
detail, such
more
likely
to
pay close
atten-
precise timing of obtaining bloodsamples. Good laboratory practice requirements proposed by the Food and Drug Administration in the United States are being incorporated into clinical studies in industry but not into academic medical research in the United Kingdom. A study cannot be ethically justified if, through lack of attention to tion
as
the
detail, its results are not valid scientifically.
Liability-The company and anyone doing volunteer work in industry are vulnerable especially to accusations, informed or
817 must therefore be (and be seen to act) in an ethical fashespecially vigilant ion. This is conducive to high standards. As Laurence stated in 19642, "... it could be argued that the consequences of any on a drug firm unmishap will be visited with especial severity " clinical dertaking experimentation...
otherwise, of unethical behaviour and they to act
Calibre
of medical personnel-Although clinicians working in
industry may have been regarded by their hospital counterparts as less competent doctors, they are generally of a high calibre and "us-and-them" attitudes have largely disappeared. Drug development is now a specialised and demanding branch of medical science which requires, and has helped to create, a mutually respectful coexistence between medical personnel in industry and hospitals. The physician in industry benefits considerably from practical responsibility for studies, and learns more about the drugs involved and the practical realities of carrying out the study than if he were only to plan studies to be conducted elsewhere. on potential volunteers-One of the possible reasons why studies involving company employees may be unethical is that employees may be under pressure to volunteer. This should not be the case and there should be adequate safeguards against pressure, including carefully and honestly conducted informed-consent interviews. In reality, the risk of pressure on medical students or other groups in hospitals may be at least
Pressure
as
great.
Facilities available-The only real potential problem may be the lack of adequate facilities should an acute medical problem such as anaphylaxis or cardiac dysrhythmia occur. The standards of physical facilities and type of staff available vary between companies, which do not, however, normally have an experienced resuscitation team or the type of facilities found in an intensive-care unit. Companies should have appropriate drugs and resuscitation equipment available but complex equipment is pointless unless there are people trained in its use; a resuscitator hanging on the wall does not ensure safety.
There are therefore some limitations to what can be done within pharmaceutical companies but danger arises only if the limitations are not recognised and the type of study undertaken is too ambitious. With adequate staff and facilities, it should be perfectly in order to conduct ethically acceptable studies on the bioavailability, pharmacokinetics, and metabolism of compounds, especially since many of the studies will involve marketed compounds on which more detailed information is required or on which a formulation change is proposed. It should also be possible to do tolerance and activity studies on appropriately selected new compounds. Valuable information can be gained about the activity of diuretics, anticholinergics, &c. in normal volunteers before studying efficacy in disease.
HOW TO ENSURE THAT SUCH STUDIES ARE ETHICAL
Selection of Volunteers Most authorities recommend that volunteers should be recruited by open invitations (for example, on notice boards) rather than by direct approach. The system at G. D. Searle, where about 40 studies have been conducted over four years, falls between the two. All employees between the ages of 18 and 65 were asked if they were interested in principle in taking part in stu-
dies ; the purely voluntary, no-obligation nature of the invitation was emphasised. Those who replied positively
pool of potential volunteers who could be approached in rotation or as required by a particular study with respect to sex or age-group. When a volunteer takes part in a study, details are recorded on his card and this guards against over-volunteering. Because early pregnancy cannot be excluded by standard laboratory screening, women of child-bearing age have been included only in studies on compounds which have been formed
a
the market for several years. Volunteers are screened for fitness by history, physical examination, blood biochemistry, haematology, and urinalysis. Normal results are a prerequisite for taking part in a study and form a useful baseline against which to compare subsequent tests. We also write to the volunteer’s general practitioner, with the individual’s consent, giving brief details of the study and asking whether there is any reason why the subject should not take part. If problems, such as hypertension or proteinuria are found, the examination is repeated and the problem discussed with the individual’s general practitioner, the subject being informed of the abnormal finding only with the general practitioner’s approval. on
What Motivates Volunteers altruism and scientific interest play some in motivation, financial reward is the main factor part as demonstrated by Hassar et awl. Payment has generally been considered ethically justifiable by those people or committees who have reviewed the question and it is probably essential in practice. A committee set up by the Association of the British Pharmaceutical Industry recommends4 that the amount paid should be reasonably related to the effort and discomfort anticipated but both Stuart-Harriss and Tyrre116 warn against the dangers of excessive payments which may constitute a bribe. The distinction between a reasonable financial reward and a bribe is blurred but the aim should be a formula which ensures adequate payment, taking into consideration the duration of the study, the degree of discomfort (such as from venepunctures) and the degree of inconvenience (such as from dietary restrictions or collection of urine or stool samples).
Although
Informed Consent Informed consent is essential but how informed is it really? Williams7 has suggested that the informed-consent interview may be a ritual which deceives both subject and doctor when the subject is uneducated, and Hassar8 used the term "unirrformed consent" in a report of a study in which most subjects appeared to have misunderstood or forgotten the information they were given. Tyrre115 has pointed out that the information given is bound to be restricted and consent is bound to be personal. Nevertheless, the investigator should explain the purpose of the study carefully, discuss the possible risks, and describe the plan of the study, drawing attention to restrictions which have to be imposed and blood or other samples which will be required. We conduct the consent interview in the presence of a third person who witnesses the volunteer contract. Insurance All volunteers at G. D. Searle are insured with life of five times their annual salary and with illness
cover
818
appropriate to the degree of disability by means of personal accident and illness policy rather than by an extension of an Employers Liability or Public Liability Policy. This ensures that in the event of an illness or death, a claim would be met without question, whereas with an Employers Liability Policy, the insurance company may expect the injured party to prove the employer’s negligence. cover
Ethical Review
Protocols must be reviewed from a purely scientific standpoint. At Searle an international system reviews all protocols for their scientific merit. In addition, a local ethical committee reviews proposed in-house studies. Committee meetings are attended by the clinical monitors whose protocols are under review for them to answer technical questions. The frequently used term, "independent ethical
review", suggests that the committee members should be connected with or chosen by anyone connected with the volunteer studies. This ideal is difficult to achieve since it is important that the members should be suitable as well as independent. Our committee chairman is a senior consultant physician at the local hospital and the other members are a consultant haematologist, a group pharmacist, a schoolteacher with a chemistry degree, and a personnel manager. The committee members accept the responsibility and demands on their time without financial or other material reward. It could be argued that this committee is not truly independent since its membership was partly determined by Searle employees. It is however probably as independent as any appropriate and effective ethical committee can be and its degree of independence compares favourably with equivalent committees in hospitals. not
CONCLUSION
I believe that the arguments for and against conducting drug studies involving normal volunteers within a pharmaceutical company show that such studies can, and perhaps even should, be done, provided their organisation and conduct are approached in a scientific and ethical mariner and provided the limitations of carrying out studies in pharmaceutical companies are recognised. The following helped to make arrangements for planning and conducting volunteer studies at G. D. Searle & Co.: Dr M. J. Asbury, Dr J. M. Clarke, Mr I. R. Harrision, Mrs M. Porteous, Dr L. E. Ramsay (now at the Gardiner Institute of Medicine, Western Infirmary, Glasgow), Dr M. J. Tidd, and Dr G. R. Venning. I also thank the members of the Ethical Committee for their help. REFERENCES 1. Wld Hlth Org. Chron. 1976, 30, 360. 2. Laurence, D. R. in Evaluation of Drug Activities: Pharmacometrics (edited by D. R. Laurence and A. L. Bacharach); p.3. London and New York, 1964. 3. Hassar, M., Pocelinko, R., Weintraub, M., Nelson, D., Thomas, G., Lasagna L. Clin. Pharmac. Ther. 1977, 21, 515. 4. The Report of the Committee to Investigate Medical Experiments on Staff Volunteers. Association of the British Pharmaceutical Industry. London, 1970. 5. Stuart-Harris, C. in International Aspects of Drug Evaluation and Usage (edited by A. J. Jouhar and M. F. Grayson); p.205. Edinburgh and Lon-
don, 1973. 6. Tyrrell, D. A. J. ibid. p.211. 7. Br. med. J. 1973, ii, 220. 8. Hassar, M., Wemtraub, M. Clin. Pharmac. Ther.
1976, 20, 379.
In
England
THE ROYAL
Now
FREE’S 150TH
ANNIVERSARY
young surgeon returning home one December upon a destitute dying girl on the steps of St Andrew’s Church, Holborn. He was unable to secure her admission to hospital and the incident distressed him so much that he immediately enlisted the help of his friends to found a medical charity to provide accommodation for the sick poor regardless of their means and without the necessity of a governor’s letter of introduction. Such was the beginning of what IN 1828
night
a
came
is now a teaching hospital of international repute, The Royal Free. And on April 17, 1978, at St. Andrew’s Church, where it all began, the hospital celebrates its 150 years of existence with a Thanksgiving Service in the presence of its Patron, Princess Alice, Duchess of Gloucester; and it will also honour the memory of the young surgeon, William Marsden. The Lancet is particularly pleased to add its congratulations, for Thomas Wakley, founder of the journal, and Marsden were contemporaries with similar ideals and humanitarian principles ; and Wakley’s son was later to be on the consultant surgical staff of the hospital and also chairman of the management committee. The hospital was first opened in Hatton Garden. There is no record of the number of beds, but it seems probable that only the homeless or the dying were actually taken into the wards and that the majority who came to the hospital were treated as outpatients. But such were the idealistic yet practical principles at its heart that in 1832 when all other hospitals refused to admit patients suffering from cholera, 700 cases were treated at The Free Hospital. In 1842 when premises formerly used as the barracks of the Light Horse Volunteers in Gray’s Inn Road fell vacant the committee of management bought the lease and in 1863 the freehold was purchased. This was the parent hospital until a few years ago; although all the original buildings were rebuilt and others added, the barrack structure of the hospital was plainly recognisable. Queen Victoria was Patron of the hospital on her accession to the throne and granted a Royal Charter in 1892, so the full derivation of its name emerges. Medical and social history was made in 1874. A small band of women, led by Sophia Jex-Blake and Elizabeth Garrett Anderson, were determined to found a medical school for women, for the Apothecaries’ Society had altered its rules to prevent women qualifying as doctors and no university would admit them; thus, the London School of Medicine for Women was founded. The pioneers were reduced almost to despair when they found that no hospital would admit women students and, unless the school was able to provide clinical instructions for its students, it was doomed. Once more the hospital gave the lead to medical and public opinion by opening its wards to women students, thereby securing the entry of women into the medical profession. In 1947 the school became coeducational by revision of its charter. As time progressed, additional hospitals became associated with Gray’s Inn Road to form the Royal Free Group. In 1974, the 850-bed new Royal Free District General and Teaching Hospital opened in Hampstead, a triumph of planning and cooperation, for the new building was actually built and commissioned while the nearby Lawn Road branch was in full use. Another event this year will be the opening of the clinical sciences building and the School of Medicine, making up the total complex of the Hospital. None can have a more favourable prospect for any aspect of service to the community, and the local population are fortunate, despite its size, in having the Free in its midst. During 1978 there will be many celebrations, some highly original (the Art Gallery exhibitions are already widely acclaimed); and the 3000 staff and 300 undergraduate students who work there each day have every right to take pride in their history and their future.
