MILLION DOLLAR DAY: Dr. John Mackey, left, and Myka Osinchuk of the Alberta Cancer Foundation, right, with Lawrence and Isabelle Giacobbo.
We all know what scientific discovery is supposed to look like: a white-lab-coated scientist, triumphantly holding up a test tube and announcing “Eureka! A cure for cancer!” perhaps before a backdrop of brave test subjects rising from their hospital beds. Of course, in the real world there is no one “cure for cancer,” because there are so many different kinds of cancers. But even when an effective treatment is found, more often than not, its eureka moment likely took place in front of a spreadsheet.
The other sort of eureka moment we like to imagine is the sudden flash of insight, when a scientist notices a pattern or combines some ideas in a new way and wonders if maybe this could be useful. But sometimes, despite the initial brilliance, a research concept does not arrive at its intended result. The creativity behind an idea has little bearing on how likely it is to be an effective treatment for cancer. And that’s why we have clinical trials.
Lawrence and Isabelle Giacobbo know the importance, and that is why they decided to donate $1.25 million this fall to the Cross Cancer Institute, to go toward clinical trials. “We decided to put it into cancer because it would touch the most people. We wanted it to go to research,” Isabelle says. The Giacobbos’ donation will help enormously with research at Alberta institutions such as the Cross, where as many as 650 patients participate in new intervention trials every year, according to Dr. John Mackey, a professor of medical oncology at the University of Alberta, who also leads the clinical trials unit at the Cross.
SWEET GIFT: The Giacobbo grandchildren were on-hand for the donation ceremony.
There are all sorts of reasons why someone might get better after taking a particular drug, and all sorts of reasons why an effective drug might fail in any given patient. Clinical trials employ controls and sophisticated statistical methods to rule out all those other explanations. But there’s more to a clinical trial than ensuring that the results are valid.
“We need to be very well organized and prepared to safely and rigorously do studies ethically,” says Mackey. A clinical trial needs to be designed in such a way as to provide benefits to – or at the very least, not to make worse off – every patient who participates. That, too, can be a difficult thing to ensure, requiring careful planning.
A lot goes into carrying out a proper clinical trial, and it can be fairly expensive in terms of time and money, even before factoring in things such as travel and the material cost of the medicine being tested. Very large international studies can cost hundreds of millions of dollars.
Where a drug promises a profit, it can be worthwhile for a big pharmaceutical company to invest in expensive trials, but not all valuable research ideas are about patentable drugs. That’s another reason why charitable donations to fund cancer research are so important.
Underwriting the cost of research specialists – the ethicists and statisticians as well as the people in white lab coats – pays off by allowing more and better studies than would otherwise be possible. For one thing, it leverages investment from drug companies, who know they can get top-notch clinical trial data from the Cross, and some of the revenue these drug trials brings in gets poured back into supporting local investigator-initiated research.
As important as it is to carry out clinical trials of new drugs to ensure they are safe and effective, there’s much more to improving treatment. A clinician who stumbles upon a neat trick for administering an established treatment, or who notices a curious pattern in the symptoms described by different patients, should be able to explore these questions in a safe, ethical and rigorously scientific manner. And that is what investigator-initiated research is all about.
Family Affair: Lawrence and Isabelle Giacobbo pose with their grandchildren.
So one innovation implemented in the Cross Cancer Institute research unit involves better access for anyone – not just veteran researchers – to the investigative resources needed for clinical trials. A new research grant application process has been introduced, and in the first year, 18 applications were received – of which three ultimately received funding. Dr. Mackey hopes to see three or four such projects approved next year.
The Giacobbos, who made their money in homebuilding, aren’t scientists, but they understand science can be full of surprises. “There are some very bright people,” says Isabelle. “Many times in research, even if they don’t find something that helps cancer, it may help with something else.”
And even if making a generous donation to support cancer research can’t guarantee a cure, it can feel pretty good on its own. “Nobody has any idea how happy we were and are that we were able to come to this decision,” Isabelle notes. Of her speech on the dim October day that the couple presented their cheque, Isabelle recalls saying, “As cloudy and dull as it is today, it’s a very sunny day that we’re able to do this.”
Phases of clinical trials
Before they reach the clinical trial stage, new drugs have usually been extensively studied in the laboratory and computer models. Clinical trials themselves are usually divided into five or six phases.
Phase 0: Traditionally, Phase 1 was the first phase of clinical trials, but in recent years researchers have started testing micro-doses of new drugs in healthy human volunteers in order to study how the drug behaves in the body. If a drug is immediately broken down by some enzyme in blood, for example, that will inform how to proceed with further study.
Phase 1: The trial team closely monitors healthy volunteers as they are given a gradually increasing dose to see when it begins to show toxicity. This helps to inform the planning of later phases.
Phase 2: Researchers attempt to establish that the drug actually has a therapeutic effect by administering it to a few dozen volunteer patients in research clinics. Most trials end at this phase if it turns out that the drug is not effective at least at doses smaller than the maximum tolerated dose from Phase 1.
Phase 3: In Phase 3, the researchers invite practicing clinicians and their patients to participate. At this stage, there may be several thousand volunteer patients receiving the drug through their regular physicians. This is the last stage before regulatory approval of the drug.
Phase 4: The original researchers continue to monitor a drug’s long-term effects after approval.
Phase 5: Members of the scientific community at large continue to study established treatments.