Discussion
The regulatory environment is an aggregate of law, regulations and
practices. A good regulatory environment is critical to support
innovation systems and enable technological advancement [9].
Guidelines are an integral element of the regulatory environment. In the
present study, we aimed to analyse the level of acceptance for changes
suggested by stakeholders for draft EMA scientific guidelines during
public consultations. Stakeholder input is a part of the process of
understanding the potential impact of the guideline, intended and
unintended. It facilitates predicting and anticipating causal
connections between the adopted guideline and observed changes in the
regulated environment. A thorough Regulatory Impact Assessment to
understand costs (externalities) and benefits which are inherently
associated with any regulation is an important part of building a
regulatory framework [10].
The process of developing guidance is overall long, up to three years.
Our results highlight that the time from the end of the consultation to
adoption is generally at least half a year but can be longer, even over
two years. There is a clear pacing problem with the accelerating speed
of science and increasing innovativeness in the research approaches,
which aim to adapt to the nature of scientific discoveries. To avoid
lengthy and rather laborious guideline development processes, the EMA
has also used other mechanisms, such as the publication of commentary or
opinion articles in peer-reviewed journals, information days or
workshops, as tools to increase clarity into how certain legislative
elements are evaluated or to support emerging practices and their
acceptability in medicines development [11]. These have proven as
helpful measures to increase clarity particularly on the more
qualitative elements in regulatory decision making. A stronger focus on
regulatory science has been proposed as necessary to address the
translation issue between science and future treatments. In Europe, the
EMA lists many new guidelines that will be developed in their Regulatory
Science Strategy to 2025 [2]. Also the Japanese regulators have
suggested to include guideline development under the umbrella of
regulatory science processes [12].
The OECD outlines that a successful regulatory strategy requires
stakeholder support, which can be achieved through constant dialogue,
publicity of the impact and consultation [10]. The results on mean
scores of the stakeholder comments indicate that the current process
appears to treat the stakeholders equally, with the average acceptance
level being close to same for accepted and rejected comments with a mean
score around 1 on a scale of 0 to 2. The differences often arise from
the nature of the guideline, whether generic or procedural or focusing
on an indication. Particularly the working parties are facing rapidly
emerging new technological approaches (safety) or novel science
(biologics) were more open for stakeholder input, which might be due to
the speed of technological development being faster than development of
associated regulatory frameworks with a higher appreciation of (scarce)
domain expertise outside of the regulatory network. The observed
differences between the EMA WPs can also be driven by elements feeding
into regulatory systems, such as behavioral aspects, decision making or
knowledge transfer mechanisms [13].
The gradual shift in the role of medicines regulation from gatekeeping
against harmful molecules to promoting public health by offering
regulatory incentives, such as additional support or faster approvals,
for products that are likely to deliver the highest health gains
[14] should not go unnoticed. Regulators have a very wide and useful
broad general knowledge given their exposure to various products through
regulatory processes but tapping onto expertise outside of their own or
immediate network can be useful. We found that that the specialist
knowledge is more readily accepted for indication level guideline when
it comes from scientists affiliated with academia rather than industry.
The opportunity cost of favoring one over the other might be to lose out
on valuable contributions [15]; scientists working in medicines
development and who can strengthen ability to translate scientific
discoveries into therapeutics or vaccines come often from the industry
side [16].
To respond to the speed of science and innovation, a better utilization
of the quadruple-helix model is required to build a competitive and
agile regulatory framework. Fostering a culture with aims at pooling all
available expert knowledge, regardless of affiliation, is in the
interest of the patient [17]. Since science is often not exact, a
document-based consultation process with the focus on individual words
or sentences may not capture the wealth of expertise in the ecosystem
and result in the best possible outcome. A true exchange across all four
stakeholder communities is likely to generate a better end result. The
research shows that the stakeholders would often prefer a discussion of
the results and implications, which would also be helpful for the
implementation process for a guideline [6].