“Traditional” trials are facing increasing costs that only the digital technologies can simplify and break down, allowing the acceleration of the whole process of pharmacological research by increasing its efficiency. The experience of Exom Group, the first European CRO to take this path.
To develop and bring to market a new drug is a very expensive investment, with estimates ranging from $650 millions to $2.9 billion, up 145% in last ten years. Although new therapeutic products and diagnostics are bringing significant improvements in the treatment of patients with serious illnesses, providing, in many cases, the first treatment approved for one condition, recent reports have found that the overall efficiency of pharmaceutical research and development (R&D) is steadily decreasing from over 50 years. Although there are many causes that variously combined are responsible of this general decline, it is largely acknowledged that the growing time and costs associated with clinical trials, are the key factors that contribute to this negative trend.
The high costs of clinical trials include mainly the difficulty in recruiting those patients suitable for the study, the presence of a significant proportion of experimental sites who don’t recruit the expected number of subjects, the lack of patient involvement in the study resulting in a high probability of abandonment and finally the difficulty in managing in real time the study conduction and the performance of the individual participating centers in a unique environment.
The pressing demand for modernisation of clinical trials is also become a priority for the international regulatory authorities. Recently Scott Gottlieb, former commissioner Food and Drug Administration (FDA) commissioner declared: ” …..Without a more agile clinical research enterprise capable of testing more therapies or combinations of therapies against an expanding array of targets more efficiently and at lower total cost, important therapeutic opportunities may be delayed or discarded because we can’t afford to run trials needed to validate them.”
The current approach to clinical trials is no longer sustainable, so it must be made more efficient and streamlined with new experimental designs, new criteria for patient selection, new parameters for assessing therapeutic efficacy and with the adoption of new and disruptive technologies that make clinical research more effective, faster and cheaper. Fortunately, both the international regulatory environment, and the technological opportunities have been ready for some time now, to support and facilitate this inevitable transformation of traditional clinical research.
Regulatory Strategies
Recent regulatory guidelines suggest that medications for precision medicine can demonstrate strong signs of efficacy in early clinical trials, even in studies where small groups of patients selected on the basis of biomarkers or other criteria suggesting a likely benefit. These studies may be the subject to an early but accurate regulatory assessment of the benefits and risks, and, if positive, allows patients to gain advance access to new important therapeutic options. As far as cancer drugs are concerned, there is great emphasis on the need to accelerate their clinical development as much as possible. Industry experts and associations of patients have highlighted three ways to improve and update the traditional clinical trial process in oncology:
- the broadening of the inclusion criteria,
- the use of real world data (RWD)
- the optimization of randomized exploratory studies.
Selecting patients according to their molecular alterations, rather than their type of disease, increases the likelihood of benefit from a specific treatment and reduces the size of the studies to fewer patients needed to demonstrate its therapeutic efficacy.
With the aim of accelerating the late stage development of oncology drugs, the same regulatory authorities propose “master protocols ” also defined as “umbrella” or “basket protocols” that test more medicines and/or multiple tumor subpopulation in parallel, without the need to develop new protocols for each test.
Another important factor for the containment of costs, is to plan studies with the “correct sample size” so that it will be possible to answer essential questions on the effectiveness of new treatments with fewer patients than in traditional studies.
For example, in the case of studies with highly active drugs, it could be possible to replace the traditional control group with the so-called “synthetics” control groups, well controlled and comparable, created with data from previous studies or from clinical databases of the real world.
Technological Solutions for the Conduct of Studies
Digital technologies are becoming ubiquitous, effective and affordable, but they are largely underused both in medicine and in clinical research, though they can revolutionize and greatly improve the way we collect, measure and evaluate clinical data, saving time and resources. Only 4% of adult patients are able to participate to clinical trials which are traditionally conducted in academic or hospital centres of the most important metropolitan areas.
The involvement in clinical trials also of peripheral hospitals or allow the centers to recruit and monitor patients remotely through telemedicine technologies would give patients access to studies from which otherwise they would be excluded, facilitating, in addition, the dissemination of results and highlighting also potential disparities in outcomes.
Today we can easily gather real-world clinical data through electronic health records (EHRs), patient registry, pragmatic studies exploiting the existing clinical infrastructure to test interventions in daily clinical contexts, surveys, pre-approval access programs, health data measured and collected directly from mobile and wearable medical devices and from smartphones.
Digital technologies therefore allow to measure the health data of participants to clinical trials, regularly in the normal course of everyday life.
Regular or continuous measurement and real-time response of an individual to a drug therapy will provide a better understanding how that drug affects the disease and its interaction with the general health of the patient.
Being able to monitor a patient remotely also allows for an early detection of adverse events to a pharmacological therapy and get a better understanding of these events when occur.
In addition to the traditional efficacy and safety parameters, with the modern digital devices we can also measure important quality of life indicators, including daily activity and the quality of sleep. Therefore, we can collect those evaluations which, while subjective, are still of utmost importance for the experience of the individual patient.
What should we expect in 2020?
Despite the current regulatory and technological ecosystem is in favour of change, many stakeholders are showing some resistance to take the road of modernisation of clinical trials. However, all indicators suggest that the traditional models of drug development are gradually leaving the place to innovative approaches that, with the patient’s centricity, will make possible the realization of radically new solutions – with more targeted interventions, shorter duration and with fewer participants, and with the analysis of real world data – thus reducing the costs, increasing efficiency and bringing faster on the market new and important therapies.
Certainly in 2020 we will see, also in Europe, this epoch-making revolution in clinical drug research. Exom Group, the first European CRO to have undertaken the modernization of clinical research processes, with its methodological and managerial expertise and the most innovative digital solutions, qualifies as the ideal partner for those for-profit and non-for-profit promoters who want to share a real change in clinical trial design and conduction.