Staying the Course
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Many valuable medical discoveries never reach the patient. They fail at a hurdle that has been giving scientists headaches time and time again: the Valley of Death. Now, a whole series of new measures has been introduced to help the situation.
One regularly reads about groundbreaking scientific discoveries in the media. However, scientists are often reluctant to answer the question of whether a discovery could result in an approved drug or therapeutic approach. For good reason, as they know how many challenges still need to be overcome successfully. One of the most intimidating issues lurks directly in front of them: the Valley of Death.
If one wants to understand the nature of the symbolic Valley of Death, one needs to understand how research works and – most importantly – which steps are needed to develop a drug or therapy. It all begins with the work of a scientist in a laboratory. The so-called basic research can be compared with the development department of a car manufacturer. This is where the planning and tweaking happens; the result is the creation of an innovative prototype. Before this prototype obtains road approval and enters serial production, it has to undergo a broad range of tests. In the world of science, these tests are known as clinical studies.
Problem of translation
Not many people know that there is an intermediate step between basic (and preclinical) research and clinical studies: the translation. And this is precisely where the problem lies. During the translation process, the prototype is examined closely and prepared for clinical trials. This step is necessary to ensure that the drug or therapy is really as good as the researcher promises and that the test drivers (or subjects) are not harmed during the clinical study.
Unfortunately, this path is full of potholes, obstacles, and abysses. This is why very few prototypes actually manage to cross the bridge between basic research and clinical trials. Most of them plummet off the bridge into the Valley of Death.
A short glance at a few figures illustrates the dimensions of the Valley of Death. In 2015, a total of 45 new drugs were approved in the US. We are not talking about 45 drugs for the treatment of spinal cord injuries, but for all kinds of medical fields. In contrast to this, as many as 1.3 million medico-scientific papers were published in trade journals during the same time period. It is estimated that only one in 5,000 prototypes manages to navigate the stony path from basic research into the clinical-trial phase.
There are many reasons for this dilemma
Crossing the translational bridge is not only full of risks, but also time-consuming and expensive. First and foremost, the researcher’s work needs to be reproduced, which means that the same prototype has to be replicated by someone else. Then many questions need to be answered. How and where should the drug be administered? Should it be applied to the lesion, injected into the blood stream or administered orally? What about the timing? Should it be administered directly after the injury was sustained? The process also includes administrative tasks such as obtaining regulatory approvals, preparing pharmacological surveys, and securing patent rights.
So who should shoulder this rather daunting workload? Should the researchers do it?
Apart from the fact that they rarely have sufficient financial and human resources, they also lack the necessary know-how. Most of them are brilliant scientists, but they have never set foot in the clinical world. That would be like entering the engineer in a race, not the racing driver.
In addition, there is no real incentive in science to advance into the clinical phase. The guilty party in this respect is the existing remuneration system. To put it simply, the researchers are, among other factors, judged on so-called Impact Points. The more Impact Points a scientist gains, the steeper his or her career, the more secure the job, and the higher the budgets. Points are only awarded when the researcher makes a valuable discovery in basic research that is published in a highranking journal. Crossing the bridge earns almost no additional points. Failed experiments obviously yield no points at all.
And above all, there are hardly any points awarded to those who attempt to reproduce the experiment of another researcher. This means that the extrinsic motivation is zero.
So who else could step up to the plate – governments, public authorities or clinics? They either lack the expertise and resources or – put quite simply – it isn’t their job. Nevertheless, governments do – in some cases – get involved in the funding process.
Ultimately, we are left with large pharmaceutical conglomerates. They are among the few who have the necessary financial resources, their own development departments and an extensive network. But even they shy away from getting involved at such an early stage, especially when the field in question is classified as a so-called rare condition. Sadly, this applies to spinal cord research. Before the bridge is crossed, it is virtually impossible to gauge the effort and potential yield. Thus, the risk for the conglomerates is simply too high. They have to operate economically and cannot afford to suffer huge losses if they want to survive in their respective markets.
How the problem can be solved
The good news is that, despite all the hurdles in spinal cord research, some prototypes have already managed to cross the bridge. These include, for example, methods for stabilizing or decompressing an injured spine, drugs for the treatment of neuropathic pain, and various therapeutic measures that aid the rehabilitation process. In addition, a number of drugs that promise to preserve or restore lost bodily functions have already crossed the Valley of Death to reach the clinical trial phase. Examples thereof are Ibuprofen, Minocyclin, and Riluzole. Those affected by spinal cord injuries would, of course, prefer if this list was much longer.
That’s why researchers, clinicians, and organisations that focus on spinal cord research are eager to solve the problem posed by the Valley of Death – from several angles.
One possibility is to intervene directly in the basic research phase and to build even better prototypes. These prototypes should be robust enough to navigate the path to the clinical phase despite all the obstacles in their way. For this purpose, there are a number of tools that are also consistently utilized by Wings for Life. In this context, research projects are only supported if it is foreseeable that they could have a clear benefit for the patients. It is equally important to set standards for the execution of experiments. The latter measure is aimed at making it easier for other laboratories to reproduce a research project.Another approach is to strengthen the bridge itself, to make it easier for prototypes to cross.
What we do
Wings for Life is also pursuing this path with its Accelerated Translational Programme (ATP*). This programme was introduced in 2016 and is targeted at supporting researchers with both funds and the necessary know-how. To this end, the researchers can access a network of experts from the fields of research, clinical studies, and industry. They encourage the researchers to send their prototypes on the journey across the bridge and assist in obtaining the required permits. They help them optimise the complex study design, offer statistical expertise, and give advice on further challenges that may arise. The result is that thanks to the efforts of them entire field, an increasing number of projects have succeeded in crossing the bridge. Today, there are 10 times more studies than 10 years ago. The hope is that this trend will continue gathering momentum and that fewer valuable prototypes will end up plummeting into the Valley of Death.
Wings for Life relies on the following tools to ensure that new therapy approaches are sufficiently prepared for the Valley of Death:
• Higher subsidies and a more targeted use thereof
• Uniform standards for conducting experiments
• Publishing of both successful and failed experiments to rule out repetition
• Promotion of bioinformatic projects for a more efficient data-collection process
• Improved knowledge exchange and collaboration
• Instilling enthusiasm for spinal cord research among young scientists
* ACCELERATED TRANSLATIONAL PROGRAMME (ATP)
Wings for Life launched its ATP to support and accelerate the transformation of scientific discoveries into clinical applications. In addition to grants, it also offers a network of experts who can help applicants successfully overcome the obstacles posed by clinical studies and the Valley of Death. The aim is to make promising treatment approaches available to patients more quickly and safely.
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