new therapy development

Developing new therapies is a long and very expensive process. A number of phases of types of studies are required.

• pre-clinical

The research that eventually leads to a new drug or treatment typically begins in a laboratory. Using the results of research into the basic genetic, cellular or biochemical processes underlying myeloma, scientists test different molecules or substances. This research may begin by using cells in a test tube (in vitro) and if promising, proceed to testing in small animals such as rats or mice (in vivo). Repeated animal trials are required to establish that a new agent is safe before it can be tested in any humans. Many molecules may be studied, but only the most promising will make the leap from pre-clinical to clinical trials.

• clinical trials

Clinical trials are research studies involving people. Because people are involved, all clinical trials must be reviewed by Health Canada and shown to be safe. Clinical trials must also be approved by the Ethics Committees of all participating hospitals. These review processes are in place to protect the safety of participants. Only those studies that pass these rigorous approval processes are allowed to recruit patients.

There are four phases or types of clinical trials, and each phase is designed to answer specific questions.

Phase I : The primary question of a Phase I trial is: “What is the best and safest way to administer the new therapy?”              A Phase I trial usually involves a small number of volunteers. The testing establishes the optimal dose for the new agent (enough that it is effective but not so much that it has toxic side effects), and perhaps the best way to administer it (e.g. orally or intravenously). A Phase I trial is an essential safety check for the new agent. Only those agents that are shown to be safe can proceed to the next phase of testing.

Phase II : The primary question of a Phase II trial is: “Does the new agent work in a selected group of patients?”                       A Phase II trial typically involves a larger group of volunteers than a Phase I trial. Volunteers are usually chosen to reflect a particular type or stage of the disease. The goal is to evaluate how effective the new therapy is in treating the disease in this type of patient. Possible side effects are also monitored.

Phase III : Only therapies that are effective, safe and have tolerable side effects can proceed to Phase III testing.           Phase III trials are usually the largest, and can involve hundreds or even thousands of patients at cancer centres around the world. Patients in a Phase III trial are usually assigned randomly to either the new therapy (often referred to as the “treatment group”) or the existing therapy (“usual care” or “control” group). If there is no existing therapy, the new agent may be compared to a placebo (“sugar pill”) but this is seldom necessary in myeloma research. The term “Randomized Controlled Trial” is derived from the random way in which people are allocated to either the treatment or control group.

The primary question answered by a Phase III trial is: “Is the new agent effective, particularly in comparison to the best available existing treatment?” To ensure expectations don’t affect the assignment of people into groups or the interpretation of the data, Phase III trials are often “blinded”. “Blinded” means the patients do not know which agent they are getting. “Double
blinding” is sometimes used so that neither the patient nor the researcher knows who is getting the new agent until the study is completed.

Phase IV : A Phase IV trial is sometimes referred to as “post marketing research”. It is research on a drug that has already been approved and is being used widely. Phase IV trials may be conducted to determine if the drug works as well in the “real world” as it did under the controlled conditions of a Phase III clinical trial. It may also be conducted to see if there are any significant long-term effects of the therapy or whether the drug could be used for other indications.