Commentary: We need more research in regulatory process outcomes
Jonathon M. Parker, RPh, MS, PhD
Cerevel Therapeutics, LLC
Cambridge, MA, USA
In the field of economics, there is a principle of diminishing marginal
productivity also known as the Law of Diminishing Returns.11https://www.britannica.com/topic/diminishing-returns
The concept is that overtime you reach a point such that additional
inputs into a system or process tend to yield progressing smaller
outputs or value. Thus, particularly for mature processes, it would be
wise to ensure one does not reach a point where input is no longer cost
effective as additional effort outweighs the anticipated gain.
In the field of regulatory science, efforts by government health
agencies related to improving the speed of regulatory reviews should be
far from removed from worrying about this concept. As any person or
group who deals with patients suffering from the legion of serious and
life-threatening diseases with unmet medical need would agree, ongoing
efforts to accelerate drug development are valuable in encouraging,
learning from, and spurring new action. Over the last 10 years, this
recognition for the need to act has been realized with new programs from
each of the three original International Council for Harmonisation (ICH)
health agencies, the European Union, Japan and the United States.
Of course, the need for these programs, however great, is not enough. We
must ensure that the acceleration activities employed result in the
desired outcomes. There is a paucity of research investigating the value
and effectiveness of pharmaceutical regulation in general. Most of the
literature focus on what a new regulatory process is, but not what it
has delivered. These examples serve as primers for the reader’s
awareness of the regulatory programs but are often created without an
analysis of the associated outcomes.
The scarcity of research into regulatory acceleration programs is not
surprising. There are many reasons such investigations are difficult to
conduct. Confidentiality laws that prevent health agencies from
disclosing certain information being just one example, but one that
serves to limit what can be ascertained and makes the compilation of
data difficult. When Drs. Muensterman, Luo and I recently investigated
expedited regulatory pathways including Sakigake, we encountered this
barrier.22Breakthrough Therapy, PRIME and Sakigake: A Comparison
Between Neuroscience and Oncology in Obtaining
Preferred Regulatory Status Elena Tomaselli Muensterman, PharmD, Yijia
Luo, PharmD, RPh, and Jonathon M. Parker, RPh, MS, PhD,Therapeutic
Innovation & Regulatory Science volume 54 , pages
658–666(2020). And while the amount of data being made available to
the public seems to be increasing each year, most researchers are still
limited to public information. This creates situations where the
valuable details were either unclear, contradictory, or completely
missing. One aspect of what makes papers like the one by Dr. Tanaka and
his colleagues so valuable, is that it is compiled by those involved in
the process who have full access to the relevant information.
Dr. Tanaka and his colleagues describe the evaluation of the Sakigake
process implemented by Japan’s Pharmaceuticals and Medical Devices
Agency (PMDA). This process serves two purposes. First, to accelerate
drug development of treatments in serious illnesses and the second to
encourage such innovation be initially performed in Japan. Focusing on
the later objective, they then describe first-in-world approvals that
were accomplished through the Sakigake process. The discussion of this
data is a significant first step in what should be an ongoing
conversation with substantial follow up.
As is the case with leading edge research, I am left with more questions
than answers. Tanaka and his colleagues cite oncology, neurology and
cardiovascular as key therapeutic areas of success. Is that trend
consistent with FDA’s Breakthrough Therapy (BTD) and EMA’s PRIME
designations? Of the 37 Sakigake-designated programs less than 25% were
co-designated BTD or PRIME, why such a disparity? What is the
approximate time saving one gets through the drug development process as
a Sakigake versus not achieving this status and why? The list goes on
and would is too long include in this commentary.
Answering these questions and many more like them could translate to
improvements in the drug development process for health agencies and the
pharmaceutical industry. This will ultimately serve to accomplish the
most important goal – to make the process more efficient in getting
important new drugs to the people who need them as soon as possible. I
always remind myself of the maxim anyone involved in healthcare should
remember – the patient is waiting .