Industry Survey on Implementation of ICH E17 Guideline

Meeting Highlights: DIA Europe 2021

Industry Survey on Implementation of ICH E17 Guideline
General Principles on Planning and Designing Multi-Regional Clinical Trials

Solange Corriol-Rohou
AstraZeneca

Dorothee Grimald
Merck

Anette Hjelmsmark
Novo Nordisk

Carolyn Hynes
GSK

Henrik Nielsen
Novo Nordisk

Maria Cristina Mota
AbbVie

Julie O’Brien
Pfizer

On behalf of the European Federation of Pharmaceutical Industry Associations (EFPIA)
@EFPIA

ow does industry perceive the impact of ICH E17 Multi-Regional Clinical Trial (MRCT) guideline in some key international countries? Are the guideline recommendations fully utilized, and how are regulatory authorities being perceived in implementing them? This article shares the results from a recent industry survey about how implementation of the E17 guideline is progressing in seven countries.

Background: Why Did the E17 Guideline Come About?

In today’s globalized drug development environment, many companies favor MRCTs to generate data that can be accepted by multiple regulatory authorities to support approval of new medicines. As well as reducing unnecessary duplication of studies, MRCTs should reduce drug lag in key markets and improve patient access to new transformative treatments. However, evaluation of data from MRCTs for drug approval can pose a wide range of challenges for regulatory authorities. As a result, work that started in June 2014 at the ICH level to provide harmonized and international guidance on planning and designing MRCTs was finalized in November 2017 with the release of the ICH E17 guideline aimed at increasing MRCT data acceptance by multiple regulatory authorities.

Industry Survey

To assess whether the ICH E17 guideline is fully utilised, the European Federation of Pharmaceutical Industry Associations (EFPIA) conducted a survey amongst its member companies to assess perceptions of benefits and barriers to the acceptability of the guideline in key countries: Japan, South Korea, China, Brazil (as ICH Members), and Russia, Saudi Arabia, and India (as ICH Observers). Data were gathered from EFPIA member companies during the summer of 2020.

The survey comprised three sections:

Section A: to gauge the activity level and awareness or understanding in industry,
Section B: to gather data on implementation of different aspects of the guideline to guide training and advocacy, and
Section C: to understand industry views on the benefits of and hurdles to implementation.

The survey readout helped identify key challenges and guide training and advocacy activities to further ICH E17 guideline implementation.

Results

Company Awareness of ICH E17 Guideline

Fifteen member companies completed the survey. Most respondents (14 of 15) reported that awareness of the ICH E17 guideline was medium or high within their company. Similarly, 13 companies rated their understanding of the benefits of implementing the guideline as medium or high (Figure 1).

Figure 1: Company awareness of ICH E17 Guideline.

Interestingly, the majority of respondents indicated that the ICH E17 training materials are not being used within their companies. Furthermore, some even commented that they were not aware of the existence of these materials; others remarked that the training materials are too general, because they are not covering how to better adhere to the ICH E17 principles in practice.

It was encouraging to see that most companies (10 of 15) were willing to modify their processes to adapt to the ICH E17 guideline, and an additional four companies said they are somewhat willing to. This shows a willingness to engage more under the right circumstances.

Country Focus: Discussions with Regulators

When asked about interactions with regulatory authorities regarding their development programs since finalization of ICH E17, all respondents confirmed they had interacted with China’s National Medicinal Products Administration (NMPA), and most companies had interacted with Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). For the other countries of interest, such interactions were only reported by around one-third of these companies, except for Saudi Arabia where only one company reported interactions (Figure 2).

chart showing discussions with regulators by country

Figure 2: Discussions with regulators by country. The graph shows sponsor responses to the following survey question: “Within your company, have you had discussions or otherwise received feedback from the regulatory authority of the country regarding development programmes since the regulatory authority implemented the ICH E17 guideline?”

In terms of the timing of such discussions, these varied by company and country, although several respondents mentioned these happened prior to phase 3. Note that the responses outlined in Figure 2 may be due to the underlying approach taken by the responding company on where to conduct clinical trials.

Requests for Local Clinical Data and Different Therapeutic Areas

These findings are linked to the answers to the question about whether a country requests local clinical data. Japan’s PMDA and China’s NMPA were often said to always request local trials (Figure 3).

Figure 3: Requests for Local Clinical Data and Different Therapeutic Areas. The graph shows sponsor responses to the following survey question: “In your experience, does the regulatory authority always, sometimes, rarely, or never request local clinical data?”

An interesting and positive trend appeared in how often local clinical data were requested since the finalization of the ICH E17 guideline: Four companies reported a change in China, one company in both Japan and Brazil, but no difference was noted in South Korea (Figure 4).

chart showing frequency of requests for Local Clinical Data and Different Therapeutic Areas

Figure 4: Frequency of requests for Local Clinical Data and Different Therapeutic Areas. The graph shows sponsor responses to the following survey question: “In your view, have you noticed a difference in how often this regulatory authority requests local clinical data since implementation of the E17 guideline?”

Companies were also asked whether they perceived any differences in how regulatory authorities have applied the ICH E17 guideline across therapeutic areas, e.g., oncology, cardiovascular diseases, and diabetes. Companies said they had noticed differences in China and Japan, with one commenting that greater flexibility was observed for products to treat rare diseases or in cases of unmet medical need.

chart showing ICH E17 guideline application across therapeutic areas

Figure 5: ICH E17 guideline application across therapeutic areas. The graph shows sponsor responses to the following survey question: “In your view, have you experienced differences in how this regulatory authority has implemented the E17 guideline across different therapeutic areas?”

Other Specific Aspects

The survey also explored greater insight into a range of different aspects covered by the guideline. Respondents were asked to rate how well various aspects had been applied in practice on a scale of one to four (four being best) in the different countries. Pooling strategies—the prespecified pooling of regions or subpopulations that may help provide flexibility in sample size allocation to regions, facilitate the assessment of consistency in treatment effects across regions, and support regulatory decision-making—emerged as an aspect where implementation could be improved in China, Japan, and South Korea (Figure 6). Can pooling of patients from Japan, South Korea, and China into an East Asian region be considered, provided that the ethnic factors are adequately understood and comparable?

line graph showing application of different aspects of the ICH E17 guideline

Figure 6: Application of different aspects of the ICH E17 guideline. The graph shows sponsor responses to the following survey question: “How well do you believe that the regulatory authority has implemented the ICH E17 guideline with respect to each aspect (on a scale of 1 – 4; 4 being best)?”

The final part of the survey gathered opinions on benefits and hurdles to implementing the guideline: Respondents were asked to select their top three from provided lists of benefits and hurdles. All companies agreed that implementation provides more efficient development of new medicines, increases the possibility of simultaneous global development and near-simultaneous registration, and optimizes patient access. More efficient use of resources for regulatory authorities and industry and obviating the need for standalone studies respectively ranked as the second and third most important benefits (Figure 7). However, respondents made it clear that companies believe they are currently far from seeing significant benefits.

bar graph showing benefits and hurdles to implementing the guideline

Figure 7: Benefits and hurdles to implementing the guideline. The graph shows sponsor responses to the following survey question: “What do you consider the most important benefits of implementation of the ICH E17 guideline? Select the top three in your opinion.”

With regard to hurdles, 14 out of 15 companies mentioned that local legislation or regulation is a hindrance, followed by the lack of awareness and understanding of the guideline by regulatory authorities and operational/logistical considerations (Figure 8).

bar graph showing hurdles to implementing the guideline

Figure 8: Hurdles to implementing the guideline. The graph shows sponsor responses to the following survey question: “What do you consider the most critical hurdles for full use of ICH E17? Select the top three in your opinion.”

Discussion and Conclusions

This survey revealed some interesting views from industry on the ICH E17 guideline and its implementation in key countries:

There is an opportunity to promote awareness of ICH E17 training materials, which are not widely used by industry respondents to this survey. This would also widen company understanding of the guideline beyond those working directly with clinical trials.
However, training materials are considered very general by those respondents who use them; these should be revised in the future, including adding more case examples.
It is probably too early to see an impact on requests for local clinical trials since implementation is still ongoing in some countries.
The need for a better understanding of the ICH E17 guideline by regulatory authorities and industry remains.
Challenges (such as pooling strategies) remain.
Finally, local legislation and/or regulation are perceived as a barrier to full implementation of the ICH E17 guideline.

The ICH E17 guideline is undoubtedly an important tool in global drug development. Despite sub-optimal use of pooling strategies, new medicines are getting approved in Japan and South Korea at about the same time as in other major markets, and China is taking a leap toward this ambition.

We encourage all stakeholders to strive for full implementation of the ICH E17 guideline recommendations, including the ability to pool subregions. This will ultimately support further development of MRCTs and their acceptance by regulatory authorities globally.

Back to Issue