Now an academic, Alexandra Carides, a statistician who worked in Merck’s biostatistics department for more than 20 years, talks to Business Review about the potential for growth on the local clinical trials market, if education and rigorous international guidelines can address the misunderstandings surrounding tests for drug approval.
By Anca Ionita
Who are you and what is biostatistics?
My area of research is clinical trials, which is about theoretical statistics applied to the planning and analysis of clinical trials. I received my PhD degree in mathematical statistics from Temple University (Group Sequential methodology, applied to clinical trials). In my second year of PhD studies I was accepted as an intern in the clinical biostatistics department at the pharmaceutical company Merck in the US. At the end of my summer internship I was offered a part-time position with the company; once I received my degree I was hired full-time. I worked there for about 20 years, most recently as associate director, scientific staff, in the biostatistics department. Last year I returned to academia full time to teach Statistics at the Fox Business School, at Temple University in Philadelphia.
How do you perceive life as a statistician?
Statistical thinking can be applied to many situations in everyday life. Statistics is a life science, because it tries to measure the unknown that surrounds us. As opposed to mathematics, where things are clearly demonstrated (proven or unproven!), statistics tries to measure the variability of life phenomena. This is where it becomes very interesting because there is a lot of room for interpretation. It is also a double-edged sword: statisticians do sometimes get a bad name because information can be misinterpreted! The same data, or the same results, can be displayed or presented in different ways. Usually, there is only one (!) correct way of presenting the information, but there could be more than one way of interpreting the same results.
Is Romania, in your opinion, a market for clinical studies? What needs to happen in Romania for the practices and standards that are applied across the world to be applied here more efficiently?
Romania is involved in a small number of multinational clinical trials. We are talking about a few trials compared with tens or hundreds of such experiments in other countries, so there is a lot of room for growth. For example, one of the large programs I worked on over 2007-2009, which was dealing with supportive oncology care, included a number of Romanian sites – hospitals and/or private clinics. Clinical trials in Romania are a market with room to grow, provided international rules and guidelines are implemented. The development of rigorous clinical trials has started in Romania in the last 15 years. We are talking about the rigor that would allow Romanian clinical trial sites to be integrated within European and US clinical practice standards. The better clinical personnel are trained and the sites developed, the higher the chances of competing for inclusion in large companies’ trials.
It’s important to have Romanian patients involved in clinical trials. Participating in such experiments is a win-win situation: on one hand, in the process of building and improving the infrastructure, you are actually improving the care for the patients that come to that clinical site every day; on the other hand, scientific proof of efficacy and the safety of new medication are obtained from the very patients who will use the medication in their own setting (cultural, ethnic, etc.). This ends up being a great advantage for the patients.
There is a lot of negative press about clinical studies, with Romania being perceived as a guinea pig of the big pharmaceutical companies, and patients allegedly not being properly informed about the risks.
But that’s not true. As a prospective patient, you are given the protocol about the trial and participation is based on informed consent, which outlines the risks and benefits of the trial. No matter how you look at it, the patient derives a clear benefit from participating in a clinical trial. Let’s take oncology trials: many cancer drugs are only studied up to phase two before they are submitted for regulatory review. If after phase two the results are strong, the company can apply for accelerated approval from the FDA in the US and/or the EMEA in Europe. Usually, the drug would subsequently be studied in larger, more diverse patient populations.
When a patient enrolls in a phase one or two clinical trial, the drawback is that the drug has not yet been well studied. But the potential benefit for a cancer patient is a life-saving drug that they are receiving earlier, before its regulatory approval. So there are many advantages to participating in a trial, but people have to be educated as to their treatment options, have informed discussion with their physician and understand which of all the ongoing clinical trials could be best for their situation.
How can the understanding of clinical trials be improved?
Through education and transparency. One has to start talking about this topic professionally. Indeed, there is a pejorative sense of participation in a clinical trial, and this is a misconception. Education via medical talk shows on TV or radio, about access to medication that is still undergoing clinical trials, is the first step in raising awareness.
As a patient with a life-threatening disease – or any disease, for that matter – first of all, you have to be aware of the possibility of participating in a clinical trial. That is an area of communication that can still be improved, especially since at a European level this issue is only now being addressed. There will soon be one repository, at the European Union level (similar to the one already operational in the USA), accessible through the internet, listing all ongoing or planned clinical trials.
When you say patients are allocated randomly, what do you mean?
The clinical development of a drug is organized in different phases. Phase one is when you are working with a few patients to look for the indication of the drug, phase two is about finding the dose and phase three consists of the large studies done before submitting the drug for approval. In my two decades at Merck, I had the opportunity to participate in clinical trials across all drug development phases. In phase three of a clinical trial, the objective is to demonstrate the safety and efficacy of the drug; therefore hundreds, sometimes thousands, of patients are enrolled. In the overwhelmingly majority of clinical trials, patients are randomly allocated to the trial treatment groups.
As a statistician, I was involved in the planning, running and analyzing of such trials. It is important to see the big picture: one can only get quality results if there is quality planning! One of the basic rules of statistical analysis is to have patients randomly allocated to treatment groups, that is, a patient has an equal chance of being enrolled in either treatment group of a study.
How much should we trust the results of the studies that are released by the media almost every day?
One of the first assignments I give to my students is to find a statement or a case in the media and approach it with critical statistical thinking. For example, there is a statement in a paper about drug A being better than drug B, based on a certain piece of information.
The assignment is to see whether the reference cited is credible and provides enough support for the claim. The students have to investigate the reference. For example, “Ten people were asked the question…”. One has to be very careful when communicating such information, as you want to help, not misinform your readers.
Let me give you an example of the misinterpretation of a study. On an Oat Bran cereal box it says something like “if you eat Oat Bran cereal you will lose weight”. If one looks at the references, which are printed on the box in a smaller font, it says that the actual study had people eating only oat bran all day long, for the entire duration of the study! It is technically correct to say that eating oat bran will make you lose weight, but this is not the entire truth. One has to be critical when accepting and using public data.
False information is worse than no information.