research as taking place only in sophisticated laboratories or highly

specialized institutions where work is devoted to scientific advances that

may or may not be applicable to medical practice. This notion, however,

ignores the clinical research that takes place on a day-to-day basis in

hospitals and doctors' offices.

Historical notes. Although the most spectacular changes in the medical

scene during the 20lh century, and the most widely heralded, have been the

development of potent drugs and elaborate operations, another striking

change has been the abandonment of most of the remedies of the past. In the

mid-19th century, persons ill with numerous maladies were starved

(partially or completely), bled, purged, cupped (by applying a tight-

fitting vessel filled with steam to some part and then cooling the vessel),

and rested, perhaps for months or even years. Much more recently they were

prescribed various restricted diets and were routinely kept in bed for

weeks after abdominal operations, for many weeks or months when their

hearts were thought to be affected, and for many months or years with

tuberculosis. The abandonment of these measures may not be though of as

involving research, but the physician who first encouraged persons who had

peptic ulcers to eat normally (rather than to live on the customary bland

foods) and the physician who first got his patients out of bed a week or

two after they had had minor coronary thrombosis (rather than insisting on

a minimum of six weeks of strict bed rest) were as much doing research as

is the physician who first tries out a new drug on a patient. This

research, by observing what happens when remedies are abandoned, has been

of inestimable value, and the need for it has not passed.

Clinical observation. Much of the investigative clinical field work

undertaken in the present day requires only relatively simple laboratory

facilities because it is observational rather than experimental in

character. A feature of much contemporary medical research is that it

requires the collaboration of a number of persons, perhaps not all of them

doctors. Despite the advancing technology, there is much to be learned

simply from the observation and analysis of the natural history of disease

processes as they begin to affect patients, pursue their course, and end,

either in their resolution or by the death of the patient. Such studies may

be suitably undertaken by physicians working in their offices who are in a

better position than doctors working only in hospitals to observe the whole

course of an illness. Disease rarely begins in a hospital and usually does

not end there. It is notable, however, that observational research is

subject to many limitations and pitfalls of interpretation, even when it is

carefully planned and meticulously carried out.

Drug research. The administration of any medicament, especially a new drug,

to a patient is fundamentally an experiment: so is a surgical operation,

particularly if it involves a modification to an established technique or a

completely new procedure. Concern for the patient, careful observation,

accurate recording, and a detached mind are the keys to this kind of

investigation, as indeed to all forms of clinical study. Because patients

are individuals reacting to a situation in their own different ways, the

data obtained in groups of patients may well require statistical analysis

for their evaluation and validation.

One of the striking characteristics in the medical field in the 20th

century has been the development of new drugs, usually by pharmaceutical

companies. Until the end of the 19th century, the discovery of new drugs

was largely a matter of chance. It was in that period that Paul Ehrlich,

the German scientist, began to lay down the principles for modern

pharmaceutical research that made possible the development of a vast array

of safe and effective drugs. Such benefits, however, bring with them their

own disadvantages: it is estimated that as many as 30 percent of patients

in, or admitted to, hospitals suffer from the adverse effect of drugs

prescribed by a physician for their treatment. Sometimes it is extremely

difficult to determine whether a drug has been responsible for some

disorder. An example of the difficulty is provided-by the thalidomide

disaster between 1959 and 1962. Only after numerous deformed babies had

been born throughout the world did it become clear that thalidomide taken

by the mother as a sedative had been responsible.

In hospitals where clinical research is carried out, ethical committees

often consider each research project. If the committee believes that the

risks are not justified, the project is rejected.

After a potentially useful chemical compound has been identified in the

laboratory, it is extensively tested in animals, usually for a period of

months or even years. Few drugs make it beyond this point. If the tests are

satisfactory, the decision may be made for testing the drug in humans. It

is this activity that forms the basis of much clinical research. In most

countries the first step is the study of its effects in a small number of

health volunteers. The response, effect on metabolism, and possible

toxicity are carefully monitored and have to be completely satisfactory

before the drug can be passed for further studies, namely with patients who

have the disorder for which the drug is to be used. Tests are administered

at first to a limited number of these patients to determine effectiveness,

proper dosage, and possible adverse reactions. These searching studies are

scrupulously controlled under stringent conditions. Larger groups of

patients are subsequently involved to gain a wider sampling of the

information. Finally, a full-scale clinical trial is set up. If the

regulatory authority is satisfied about the drug's quality, safely, and

efficacy. it receives a license to be produced. As the drug becomes more

widely used, it eventually finds its proper place in therapeutic practice,

a process that may take years.

An important step forward in clinical research was taken in the mid-20th

century with the development of the controlled clinical trial. This sets

out to compare two groups of patients, one of which has had some form of

treatment that the other group has not. The testing of a new drug is a case

in point: one group receives the drug. the her a product identical in

appearance, but which is known to be inert—a so-called placebo. At the end

of the trial, the results of which can be assessed in various ways, it can

be determined whether or not the drug is effective and safe. By the same

technique two treatments can be compared, for example a new drug against a

more familiar one. Because individuals differ physiologically and

psychologically, the allocation of patients between the two groups must be

made in a random fashion; some method independent of human choice must be

used so that such differences are distributed equally between the two

groups.

In order to reduce bias and make the trial as objective as possible the

double-blind technique is sometimes used. In this procedure, neither the

doctor nor the patients know which of two treatments is being given.

Despite such precautions the results of such trials can be prejudiced, so

that rigorous statistical analysis is required. It is obvious that many

ethical, not to say legal, considerations arise, and it is essential that

all patients have given their informed consent to be included. Difficulties

arise when patients are unconscious, mentally confused, or otherwise unable

to give their informed consent. Children present a special difficulty

because not all laws agree that parents can legally commit a child to an

experimental procedure. Trials, and indeed all forms of clinical research

that involve patients, must often be submitted to a committee set up

locally to scrutinize each proposal.

Surgery. In drug research the essential steps are taken by the chemists who

synthesize or isolate new drugs in the laboratory; clinicians play only a

subsidiary part. In developing new surgical operations clinicians play a

more important role, though laboratory scientists and others in the

background may also contribute largely. Many new operations have been made

possible by advances in anesthesia, and these in turn depend upon engineers

who have devised machines and chemists who have produced new drugs. Other

operations are made possible by new materials, such as the alloys and

plastics that are used to make .artificial hip and knee joints.

Whenever practicable, new operations are tried on animals before they are

tried on patients. This practice is particularly relevant to organ

transplants. Surgeons themselves—not experimental

physiologists—transplanted kidneys, livers, and hearts in animals before

attempting these procedures on patients. Experiments on animals are of

limited value, however, because animals do not suffer from all of the same

maladies as do humans.

Many other developments in modem surgical treatment rest on a firm basis of

experimentation, often first in animals but also in humans; among them are

renal dialysis (the artificial kidney), arterial bypass operations, embryo

implantation, and exchange transfusions. These treatments are but a few of

the more dramatic of a large range of therapeutic measures that have not

only provided patients with new therapies but also have led to the

acquisition of new knowledge of how the body works. Among the research

projects of the late 20th century is that of gene transplantation, which

has the potential of providing cures for cancer and other diseases.

SCREENING PROCEDURES

Developments in modem medical science have made it possible to detect

morbid conditions before a person actually feels the effects of the

condition. Examples arc many: they include certain forms of cancer; high

blood pressure; heart and lung disease; various familial and congenital

conditions; disorders of metabolism, like diabetes; and acquired immune

deficiency syndrome (AIDS), the consideration to be made in screening is

whether or not such potential patients should be identified by periodic

examinations. To do so is to imply that the subjects should be made aware

of their condition and, second, that there are effective measures that can

be taken to prevent their condition, if they test positive, from worsening.

Such so-called specific screening procedures are costly since they involve

large numbers of people. Screening may lead to a change in the life-style

of many persons, but not all such moves have been shown in the long run to

be fully effective. Although screening clinics may not be run by doctors,

they are a factor of increasing importance in the, preventive health

service.

Periodic general medical examination of various sections of the population,

business executives for example, is another way of identifying risk factors

that, if not corrected, can lead to the development of overt disease.

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