Did you know that on average in the US it takes 12 years for an experimental drug to get from the laboratory to your medicine cabinet? That journey is long and expensive. The fact is most drugs never make it to market. Only 5 in 5,000 drugs that enter preclinical testing progress to human testing. Of those 5, only one will likely be approved.
Ewoud Jan van Hoogdalem, PhD, RPh, ClinPharm, Vice President, Global Scientific Affairs, PRA Health Sciences provides insight into the drug development process—the challenges and the hope.
One of the great privileges at PRA Health Sciences is having the opportunity every day to make a difference in the lives of people with a medical condition. With our clients, we work at the forefront of new insights in diseases, using these new insights for the successful development of new treatments for hard-to-treat conditions. Every day, PRA experts are involved in the clinical testing of new treatments for diseases for which the current treatment options are limited or even absent: new antibiotics that are effective against resistant bugs like MRSA, new pain treatments that are less addictive and safer than today’s pain killers, treatments for neglected diseases with few patients worldwide (‘orphan diseases’) such as muscular dystrophies, metabolic disorders and cystic fibrosis. These are just a few named examples, numerous other important projects in today’s PRA portfolio remain unnamed, but are as active and relevant.
The common theme among all projects is that these treatments must be carefully tested for two main purposes: do these novel treatments have a meaningful benefit in patients, and are they sufficiently safe at the right dose? The typical pathway of any project is that after extensive testing in the lab, including in models for the disease and in models for safety, the most promising treatment is moved from the ‘pre-clinical’ (i.e. not yet in humans) phase into the clinical phase.
Every day, PRA experts are involved in the clinical testing of new treatments for diseases for which the current treatment options are limited or even absent
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March 15–24, 2018
The clinical phase typically starts with small studies (‘Phase I trials’) in humans, evaluating safety of the new treatment, and studying uptake of the product in the human body and its elimination from the body. If possible in this early phase, we look at hints for beneficial effects as well. When the new treatment turns out to be promising, we continue with larger studies in patients (‘Phase II trials’), and when we expect that we are clear on the best dose(s) for patients we confirm our expectations in very large ‘Phase III’ pivotal trials in patients.
When the new treatment continues delivering on expectations, our client may be able to secure ‘regulatory approval’ and thereby be allowed to market the new product for the disease in different countries. After this approval, clinical testing often continues, to confirm safety of the product in the ‘real world’ and/or to prove efficacy and safety in other patient groups. PRA is active in and specialized in all these clinical test phases that are executed in PRA-owned clinics (we have 8 of these world-wide), or in external clinical units, practices and hospitals.
Why do so many clinical studies fail?
It is fair and important to add that many potential treatments do not make it through the clinical test phases, through approval, and to the prescription pad and into the pharmacy. Generally speaking, of all test products in clinical Phase I, an appalling number, approximately 90%, fail somewhere in the test process. Why? Often it is because the new treatment is insufficiently safe or insufficiently efficacious. But this is not the complete story; products also fail because they lack the right testing plan (‘development plan’), the right development team, sufficient resources, and/or because of cutting corners. At PRA we want to make a difference by helping our clients with the right plan and the right team, and testing the potential novel treatment with the best designed and executed clinical tests.
The transition from the preclinical phase into the clinical phase is a very important milestone, marked by the ‘first-in-human study’. The preclinical phase focuses on collecting all relevant information on the effects, the safety and many other important characteristics of the new treatment in the lab, to enable an initial forecast of behavior in humans. At the first-in-human milestone these expectations are to be confirmed by actual data in humans.
The objective of the first-in-human study is to learn as much as possible about the behavior of the new treatment in humans while keeping the study do-able. Outcome of the study is to inform decision-making for the next clinical development steps in the cascade of events towards an approved new treatment. The prerequisite is that the first-in-human study is designed in such a way that participation is safe for the subjects, and that risks are well understood and minimized. Obviously, this holds for all clinical tests with new treatments, and also after approval of a new treatment. The learning on safe use in daily clinical practice continues. The particularity about the first-in-human study is that, by definition, the new treatment has never been evaluated in humans before. Consequently, we need to be very smart, alert and persistent in our interpretation of what has been done in the pre-clinical phase, and to be determined to ‘do the right thing’ in the design and execution of the first-in-human study.
Designing first-in-human studies and discussing these with our clients is our daily business in PRA. We execute many of these studies a year. While this is commonplace, the word ‘routine’ is not a word that comes to mind when being engaged in first-in-human studies. Like every patient is unique, every novel treatment represents its own case, requiring a tailored approach to do the right thing for the project and its sponsor.