JUL AUG 2013

singapore health

Opinion

17

ts not really clear how guinea pigs came into the picture. But the refrain Doc, I dont want to be a guinea pig! is usually made, sometimes in jest, when a junior doctor is about to carry out a minor procedure such as setting up a drip. Or when a patient is told that the regular or standard therapy no longer seems to work for him and he should consider novel therapies. Guinea pigs are actually rarely used for medical research, and never for learning minor procedures. Mice could be quite miffed by this refrain though. They are the ones most frequently used for research. But rarely are their contributions acknowledged by: Doc, I dont want to be a mouse! Humour aside, do patients benefit from participation in clinical trials, and how are they protected if they do? What clinical trials entail Medical research on animal or human subjects are strictly screened and monitored by the Institutional Animal Care and Use Committee in the case of animals, or by an Institutional Review Board (IRB) in the case of humans.

Clinical trials are governed by strict inclusion and exclusion criteria and only a very specific group of patients is eligible for any given clinical trial.
Both organisations ensure that research subjects are appropriately and well taken care of. Additionally, an IRB is guided by the principle of equipoise when considering approval of all clinical trials on human subjects, except for well or non-ill patients in phase I studies. A position of clinical equipoise occurs when there is genuine uncer taint y within the expert medical communit y not necessarily on the part of the individual investigator about the preferred treatment, according to a paper by Benjamin Freedman published in the New England Journal of Medicine in 1987. What this means is that at that point in time, the scientific world does not have any definite data that any one of two or more possible treatment options available is the most efficacious for the patient. An individual doctor, the

patient or indeed anyone, can sometimes hold the firm opinion that a specific treatment is the best even when no definitive data is available. Such an opinion can turn out to be right, or wrong. Holding such a belief in the absence of definitive data can prevent the patient from getting better treatment, and even be harmful, in the worst-case scenario. When it is scientifically unclear which of two or more possible treatments is best for the patient, a position of equipoise exists. This can only b e re s olve d by conducting a scientifically rigorous study. For some medical conditions, this would in fact be the only way to be fair to the patient in question. For example, in a randomised controlled or a phase III trial, one of two treatments for the same clinical condition is randomly assigned to the patient by a computer programme. Either therapy or treatment arm is likely to have its own associated risks and potential benefits. Without a properly conducted clinical trial, there will be insufficient scientific data for doctors to know which treatment benefits a patient better. During the course of the study, if data emerges that one therapy is better for patients,

Benefits to patients Clinical trials are certainly important for society. But can individual patients benefit from clinical trials?

Doc, I dont want to be a guinea pig!

For patients who no longer respond to standard treatment, participating in a clinical trial offers the possibility of a cure
By Professor Pierce Chow

Photo: alecia neo

the trial will be stopped and the better therapy will be recommended. In a double-blind study where neither the doctor nor patient knows which of two drugs a patient is allocated to, an independent Data and Safety Monitoring Committee decides if the study should be stopped. The members of the committee have no direct contact with the patients in the trial but have full access to data. Clinical trials are governed by strict inclusion and exclusion criteria and only a very specific group of patients is eligible for any given clinical trial. An IRB, for instance, will consider the condition of the patients eligible for the trial when considering approval of a clinical trial. Using cancer as an example, if there is standard therapy available for the stage of that specific disease, this therapy must be used first. Only when the standard therapy is no longer effective, or if the standard therapy is not suitable for the patient, can the patient be enrolled into a clinical trial. Some phase I trials enrol both patients as well as healthy individuals who are compensated for their participation. Phase I studies can have different aims, such as to investigate what doses of a new drug are appropriate for patients, and may also be different from later phase clinical trials which investigate how effective the new drugs are. Phase I trials are very important, as without them, no new therapies will be introduced.

When standard therapies are no longer applicable or useful for the patient, new therapies may avail. But even if costs are not an issue, such new therapies are not usually available outside the tightly controlled and legislated environment of a clinical trial. Because clinical trials are very closely monitored by regulatory authorities, patients in clinical trials are also more closely looked after than patients with similar conditions not on clinical trials. In countries with a developed medical and scientific culture, patients sometimes travel long distances to avail themselves of the new therapies offered by clinical trials, knowing that such treatments may be their only hope for recovery. Very often, they are referred by their altruistic regular physicians, who may have been the first to inform their patients that a trial being conducted at a particular institution may benefit them. So in some circumstances, it may not be a bad idea to be a guinea pig. Hmm... I mean a mouse.

Professor Pierce Chow is a Senior Consultant of Singapore General Hospitals Depar tment of General Surgery, and Course Director at the DukeNUS Graduate Medical School, Singapore. He has published extensively on hepato-biliary cancers and gastrointestinal stromal tumours, and carried out both pre-clinical and clinical research on brachytherapy in hepatocellular carcinoma and pancreatic cancers. Professor Chow has received two National Medical Research Council Research Fellowships.