Clinical trials 101

PHOTO: Clinical trials 101

Clinical trials are an essential component of medical science.

Without them, we would not be able to know definitively, whether or not a particular drug or treatment, screening technique or preventive method, works as we expect it to in humans.

Because while laboratory and animal tests are a useful precursor to establishing the mechanisms and efficacy of a particular drug, you never know how it might actually react in the complex human body.

According to the World Health Organisation, a clinical trial is defined as "any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes".

Due to the high costs of running a clinical trial, which can go up to millions of US dollars, most trials are financed and run by major pharmaceutical companies.

The process of developing a new drug usually starts in the molecule "library" of these companies. These unique molecules have different properties, which may lend themselves to treating or diagnosing various diseases.

Based on initial research results, scientists will then further explore the safety, efficacy and bioavailability (the proportion of the molecule that actually reaches the targeted cells in the body) of the molecule via laboratory and animal studies.

If the molecule proves successful in these initial stages, then the next step is testing in humans.

This is done in clinical trials, which are divided into four phases: I, II, III and IV.

In phase I, the drug is tested on a few healthy volunteers in order to evaluate its safety in humans, determine the dosage range, and to observe any side effects.

If the drug proves to be safe, then it is moved on to phase II to see if it can actually treat the disease it is targeted at.

At this stage, the number of trial participants is increased, and consist of patients with the condition the new drug is meant to affect.

Phase III involves thousands of patients, and is frequently expanded to include several medical centres across different countries.

During this phase, the new drug is compared to either the current standard treatment or a placebo, to see if it provides a statistically significant improvement over either the standard treatment or the placebo.

Running the trial simultaneously in several countries allows the drug to be tested on different ethnic populations, more patients to be recruited more quickly, decreased operational costs by including developing countries in the trial, and allowing potential life-saving therapy to a wider patient population.

Factors that affect the choosing of international trial sites include the type of medical infrastructure and regulations present, the size of the potential market for the drug in that country, the medical expertise available, and the willingness of local specialists to carry out the trial, among others.

Phase IV, also known as post-marketing surveillance, is when the product has already been made available to the public. Among the areas monitored in this phase are long-term side effects of the drug and its interaction with other drugs or products for patients on multiple medications.

Ethics and volunteers

Because of the potential danger in introducing a new chemical substance or mechanical device into humans, clinical trials must undergo stringent regulatory and ethical approval procedures.

Medical and research centres usually have their own ethics committee that examines and approves or rejects any applications to run clinical trials in their centre.

Many countries also have laws and/or government agencies that regulate such trials within their own borders.

On an international level, pharmaceutical companies usually seek the approval of the United States Food and Drug Administration (FDA) and/or the European Medicines Agency - the two most influential drug regulatory agencies in the world.

Researchers themselves are also supposed to be ethically governed by the Declaration of Helsinki, which is "a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data" developed by the World Medical Association, and the Nuremberg Code, a set of medical research principles that grew out of the World War II Nazi experimentation on Jews and other minorities.

One of the essential practices in recruiting patients for a clinical trial is informed consent, which means that the patient needs to be told both the potential benefits and risks of the drug, the details of the study, and any potential side effects.

Patients are usually not paid for their participation, although they generally receive free healthcare for their condition while in the trial, and may receive reimbursement for things like transportation and food.

While many might view testing out an unproven product in your own body as being too risky and scary, chronic myeloid leukaemia patient S. Kamakshi feels that patients should help medical science when they can.

As her husband H. Subramaniam says: "Our thinking is that the drug companies want FDA approval to market their product; if they are not very sure after testing on animals, they wouldn't move onto humans."

As Kamakshi's Singaporean haematologist, senior consultant Dr Charles Chuah from Singapore General Hospital, says: ""Medical discoveries do not happen by chance. Through clinical trials like the ones that Madam Kamakshi had participated in, we learn how to diagnose, treat, cure or prevent diseases.

"For patients who do not respond to any forms of treatment, participating in a clinical trial gives them renewed hope as they will be given new treatment that may not be available in the market.

"These trials are conducted in many hospitals around the world. Our participation in trials is important. Not only do patients benefit from new treatment, but we are also able to determine if the new treatment is safe and effective in our local population."

He adds: "Observations that trial patients share are useful. They help us manage their condition and enhance our understanding of side effects that other patients in the trial may have.

"Through inspiring patients like Madam Kamakshi who participate in clinical trials, we have learnt and benefited tremendously to advance medical and scientific knowledge, and most importantly, to help other patients in the future."