Joanne Yeoh

The success of a clinical trial is crucial in ensuring a drug is approved to be marketed and the process involves a significant amount of cost. The likelihood of a drug at Phase I making it all the way to the market tentatively has a 14% success rate.

Therefore, it is critical for pharmaceutical companies to ensure that the planning and implementation of a clinical trial strategy is effective in order to obtain the desired results. There are many factors which can contribute to the successful conduct of clinical trial; such as, the selection of high-quality clinical sites and complexity of the clinical trials protocol as it plays a major role in determining the successful rate of the clinical trial. However, the most important factor in determining the success of a clinical trial lies in the co-operation and teamwork of all the stakeholders involved, such as the pharmaceutical organization, the CRO, the principal investigator and the clinical trial support team. In this article, the authors describe the impact of a Strategic Alliance (The ICR-CRM-IQVIA Network) in to facilitate operational success at the clinical trial site level in Malaysia. Pivotal success factors include enhanced site relationship, transparent communication channels, open information-sharing, and the on-going development of new processes and tools to overcome operational inefficiencies and challenges.

Regardless of the industry, business leaders agree that developing long term, mutually beneficial relationships, is critical to business success. Recognizing the importance of strategic alliance, ICR-CRM-IQVIA came into collaboration, with the goal of a site-centric, transparent, relationship-based commitment that empowers and facilitates operational improvements to clinical trials. Critical components, such as tangible improvements to clinical trial operations between the stakeholders and the trial sites, are among the key success factors of this collaboration. In the context of strategic alliance, it can be defined as an agreement between firms to do business together in ways that go beyond normal company-to-company dealings but fall short of a merger or a full partnership.

Clinical Research Malaysia (CRM) is a provider of clinical research services that offers site management services to investigators conducting clinical research within hospitals and was established by the Malaysian government to entice sponsors to conduct trials in the country. CRM has a team of approximately 130 trained study coordinators based at various sites conducting industry sponsored research.

The Institute of Clinical Research (ICR) functions as the clinical research arm of the Ministry of Health (MOH) Malaysia to support and facilitate activities in its hospitals. In this collaboration, the major role of ICR is to provide trained, expert investigators and site availability in order to coordinate industry-sponsored research in the Ministry’s facilities.

IQVIA is a global provider of advanced analytics, technology solutions and contract research services to the life sciences industry, from drug clinical development to commercialization.

Since the collaboration began in 2013, a network of sites has been established under the ICR-CRM-IQVIA network. In the beginning, six MOH hospitals have been identified and selected to join the program based on rigorous criteria, among them the capability and capacity of the sites, and the commitment to operational efficiency and improvement. Currently, the network has expanded to a total of 18 MOH hospitals.

To ensure the success of the network in maximizing the research productivity, dedicated alliance managers from CRM and IQVIA were assigned to manage the relationships and performance of these sites. Alliance managers also act as ambassadors for their assigned sites, supporting business development and support system process improvement. The alliance managers maintain regular communication with assigned sites on:

Developing close working relationships with site staff and in-depth knowledge of processes

Project issues like enhancing recruitment through parallel channels for patients to access clinical trial

Non-project issues such as overall site performance, contract timeliness, business strategy, mutual pipelines/planning to drive future growth.

Close monitoring performance (start-up timelines, patient enrollment and quality). KPIs are agreed upon collectively by the Joint Executive Steering Committee. Set up from the inception of the site alliance, these regular meetings include shared discussions on study status, new studies, outstanding issues, forecasted deliverables (e.g., first patient enrolled), process alignment, and other topics.

Initiatives to drive participation and productivity

It was that noted from the collaboration, that the performance of the clinical trial sites within this network have improved tremendously from 2016 till 2019. Among them are:

Significant increase in IQVIA’s trial patient contribution from this network in Malaysia, 28% (2016) to 73% (2019).

Significant increase in patient enrolment from this network from 2016 to 2019, increased 34% in patient numbers.

Significant reduction in contract timelines from 2016 to 2019, with timelines reduced to 49%.

Maintaining the average and GCP protocol compliance at above 95%, with the increasing number of studies conducted at these sites from 2016 to 2019.

Greater performance of clinical trial sites has also led to the increase in the number of clinical studies in Malaysia, yearly. This is in line with the vision of the alliance which is to establish Malaysia as a preferred destination for sponsored clinical research.

Figure 1: Percentage of Patient Contribution from ICR-CRM-IQVIA network sites into IQVIA managed studies in Malaysia. Source data from IQVIA

Figure 2: Percentage of Patient Enrollment of studies from ICR-CRM-IQVIA network. Source data from IQVIA

Figure 3: Clinical Trial Agreement Timeline (from initial draft to executed contract) of studies in ICR-CRM-IQVIA network. Source data from IQVIA

In order for the strategic collaboration to sustain a competitive advantage in clinical trial, the network needs to be ready for more challenges for the future. Priority remains for the continued focus of the network to be the center of excellence with successful achievement of the performance indicators, however, maintaining high performance is more challenging than attaining it.

It is clear that advancing technology and its integration in the way it implemented in clinical trials will be the focus in coming years. The network sites must be ready to embrace and adopt new clinical trial technology such as adapting electronic tools and methods in clinical trial activities. The network and its ability to generate and collaborate on innovative ideas rooted in the reality of clinical practice will be critical to partners in understanding where technology gaps are and how to best fill those gaps. For instance, there have been active discussions around remote, decentralized, and virtual trials, especially in recent times. The required technology adaptions include and are not limited to electronic informed consent, telemedicine, electronic filing of study documents, etc. IQVIA has the ability to front this technology but would require support of CRM and ICR for successful implementation at the site level. CRM and ICR would have the critical role in evaluating the technology from a local perspective and in addressing the opportunities and possible limitations.

The success of the clinical trial conduct proves that the importance of the strategic alliance’s role for the sustainable competitive advantage and stimulate further conceptualization and research on the subject.

The advantage of the strategic alliance is not limited to the improvement of the organization performance, but it can also be a method for significant learning and knowledge acquiring, which eventually leads to sustainable competitive advantages for all partners. Regardless of the challenges ahead, what is definite is that relationships are the foundation upon which this network is built on and the strength of this network will continue in sustaining it long into the future.

is the Clinical Operation Head of Department, both of Clinical Research Malaysia

is the Associate Director, Patient & Site Services, SEA R&D Solutions; and 

is the Head of R&D Solutions, Southeast Asia, both of IQVIA.

The Changing Landscape of Research and Development. Innovation, Drivers of Change, and Evolution of Clinical Trial Productivity, Institute Report, Apr 23, 2019.

Wong, C. H., Siah, K. W., & Lo, A. W. (2019). Estimation of clinical trial success rates and related parameters. Biostatistics, 20(2), 273-286.

Wheelen, T.L. and Hungar, D.J. (2000), Strategic Management and Business Policy, 7th ed., Addison-Wesley Publishing Co., New York, NY, pp. 125-134, 314.

https//clinicalresearchmalaysia.my (n.d.). Services. Retrieved June 04, 2020, from https://clinicalresearch.my /services/

Webmaster. “Client Charter.” Clinical Research Centre, 24 Dec. 2013, 

Culpan, R. (2008). The role of strategic alliances in gaining sustainable competitive advantage for firms. management revue, 94-105


Articles

A discussion of the impact of a strategic alliance in to facilitate operational success at the clinical trial site level in Malaysia. 

The ICR-CRM-IQVIA Research Network Collaboration Experience

The International Conference on Harmonization- Good Clinical Practice (ICH-GCP) is an international ethical and scientific quality standard that ensures the rights, safety, and well-being of clinical trial subjects are protected and that the clinical trial data generated are credible.

	Malaysia’s GCP guideline was developed by the National Pharmaceutical Regulatory Agency (NPRA) in 1999. This guideline adopts the basic principles outlined by ICH-GCP with some modifications to adapt to local conditions.2 The object of the Malaysia’s GCP guideline is to ensure that drug-related trials in the country are conducted in accordance with international ethical and scientific standards.

 Although there is currently no legislative requirement for GCP training, mechanisms were put in place to ensure that Investigators are trained on GCP. For example, it is mandatory to submit a copy of the principal investigator’s GCP certificate when obtaining regulatory approval from NPRA to conduct a clinical trial.

 In addition, all investigators must submit their GCP certificates for the ethics committee’s approval in Malaysia.

 Since the first edition of the Malaysian guidelines for GCP to the current fourth edition, approximately 12,000 clinicians have been GCP certified.

	It is recommended for GCP-certified personnel to be retrained on GCP guidelines every three years in order to stay current with updated regulations, standards, and guidelines.

 To that end, Clinical Research Malaysia (CRM), a research organization founded by the Malaysia Ministry of Health (MOH), has taken the initiative to conduct GCP refresher workshops for clinicians, nurses, allied health professionals, and study coordinators who have been certified with Malaysian GCP. The objective of the workshop was to provide a review on the principles of GCP, to improve participants’ skills and knowledge on managing the conduct of a clinical trial, and to share recommendations on how to conduct a GCP-compliant clinical study.

Since the first workshop on Oct. 4, 2016, CRM has conducted 31 GCP refresher workshops throughout Malaysia to about 450 participants at no cost. The majority of the participants are clinicians, nurses, and allied health professionals from government hospitals who are involved in clinical trials. Over the course of the conduct of the workshop, modifications have been made based on participants’ feedback to improve the quality and learning outcome of the workshop. A summary of the changes in the workshop agenda is listed in Table 1. As shown in the table, the pre- and post-workshop assessment test was introduced March 16, 2017, in order to evaluate the effectiveness of the workshop on participants’ knowledge regarding GCP. In this article, we analyze the pre- and post- workshop assessment score for workshops conducted since March 16, 2017.

	Before the start of the workshop, participants were required to complete 20 multiple-choice GCP-related questions (pre-workshop assessment). The questionnaires were then collected before the start of the workshop. When concluded, participants were then required to complete the same set of questions (post-workshop assessment). Participants were given 30 minutes to complete the questionnaire.

	The average score of the pre- and post- assessment results from participants of the same workshop was then calculated, which constitute one set of data points.

	The average score of pre- and post- workshop assessment from each workshop conducted since the introduction of the assessment on March 16, 2017, were compiled. Of the 28 workshops conducted since then, five workshops’ data could not be retrieved, hence, only 23 sets of data point were analyzed.

	The compiled average score of pre- and post- workshop assessment were then compared using Microsoft Excel’s T-test, assuming unequal variance to evaluate if there is any significant improvement in the average assessment score after the workshop.

Table 2 shows the compiled data from 23 workshops. Four hundred and twenty participants completed the pre-workshop assessment, and 434 participants completed the post-workshop assessment. On average, there is 20% improvement in the assessment score before and after the workshop.

	As shown in Table 3, the p-value is less than 0.05, suggesting that the improvement in the score is significant after participants attended the GCP refresher workshop.

	Training of investigators and allied health professions involved in clinical trials on the regulations and standards that govern clinical trials is important to improve the quality of studies and ensure maximum safety for study subjects. A survey among clinical researchers in Saudi Arabia on their ICH-GCP knowledge found that there is a poor understanding of investigators’ responsibilities on informed consent, and prompt reporting to the ethics committee.

 Hence, refreshing investigators’ awareness of their responsibilities could help to improve the performance of investigators in conducting clinical trials, particularly in these important ethical aspects.

	The GCP refresher workshop conducted by CRM fulfills its objective to provide revision of the principles of GCP to participants, with more than an average of 20% improvement in assessment score after the workshop.

	The factors that potentially contribute to the success of the CRM GCP refresher workshop in improving participant’s scores are explored ahead.

	Case studies were included for informed consent, adverse event reporting, and protocol deviations, for discussion.

	Participants were given real-life scenario case studies and they were required to answer guided questions in groups. The study has shown that case studies are more effective than textbook reading at promoting the learning of key concepts and comprehension of the relevance of concepts to real-life scenarios.

	Several methods were used to make the workshop interactive, such as games, quizzes, videos, group activities, and group discussion. Active engagement of participants helps to retain information.

	Trainers would also actively engage participants by asking questions and encouraging participants to share their experiences and practices. Regulations of clinical research can be understood more easily when participants can reflect the principles based upon their own experience.

	Participants were given an evaluation form at the end of the workshop to provide their feedback and opinion. Based on their feedback, modifications were made to improve the conduct of the workshop.

	The first GCP refresher workshop was a half-day (four-hour) workshop. Participants reflected that the workshop felt rushed and suggested to make it a full-day course. Subsequent workshops were then conducted one full day (eight hours) to ensure participants can learn at a better pace, contributing a better learning outcome.

	Based on early feedback, participants would like more activities, especially for safety reporting and protocol deviations. Modifications based on this feedback include the shift from a lecture-style workshop to an activity-based workshop. Presentation slides were also revised to be more concise to retain attention.

	Following feedback from participants, current edition Malaysian GCP guideline booklets were provided for participants to refer to during the workshop.

	It is important for investigators and allied health professionals who are involved in clinical studies to be trained on the latest GCP guidelines. GCP refresher workshops conducted by CRM were effective in refreshing participant knowledge on GCP guidelines. The success of the workshop could be attributed to providing case studies for discussion and interactive activities, as well as taking participant feedback into consideration. We would recommend other governing bodies to support the conduct of similar interactive workshops in their jurisdiction and to consider participant feedback for continuous improvement.

		Good Clinical Practice Network, n.d. ICH GCP Good Clinical Practice. Retrieved 05Nov2019 from: 

		National Pharmaceutical Regulatory Agency, 2018. Malaysian Guideline for Good Clinical Practice 4th Edition. Introduction to Malaysian Guidelines For GCP, Page 8.	

		National Pharmaceutical Regulatory Agency, 2017. Malaysian Guideline for Application of Clinical Trial Import Licence and Clinical Trial Exemption. Retrieved Nov. 5, 2019 from: 

http://www.nccr.gov.my/view_file.cfm?fileid=33

		Society Of Clinical Research Professionals Malaysia, 2016. A Guide to Conducting Clinical Trials in Malaysia, First Edition. Retrieved Nov. 5, 2019 from: 

http://www.clinicalresearch.my/wp-content/uploads/2017/03/A-Guide-to-Conduct-Clinical-Trials-in-Malaysia.pdf

		National Pharmaceutical Regulatory Agency, 2018. Malaysian Guideline for Good Clinical Practice 4th Edition. Forward to the Fourth Edition, Page 4.	

		National Institutes of Health, n.d. Good Clinical Practice Training. Retrieved 05Nov2019 from: 

https://grants.nih.gov/policy/clinical-trials/good-clinical-training.htm

		Al-Nomay NS, 2015. Compliance with ICH-GCP Guidelines among the Saudi Health Care Professionals: Should Saudi Arabia Conduct Widespread ICH-GCP Training? 

s. 2015; 1(2): 75-82. Retrieved Nov. 5, 2019 from: 

https://pdfs.semanticscholar.org/0112/2b2e7c0fdd762172251e807c273fcb4a399a.pdf?_ga=2.112527492.1640531090.1574928919-1845614418.1571207552

		Bonney KM, 2015. Case study teaching method improves student performance and perceptions of learning gains. 

. 2015;16(1):21–28. Retrieved Nov. 5, 2019 from: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416499/

		Robin L. Bachelor Patrick M. Vaughan Connie M. Wall, 2012. Exploring the Effects of Active Learning on Retaining Essential Concepts in Secondary and Junior High Classrooms. Retrieved Nov. 5, 2019 from: 

https://files.eric.ed.gov/fulltext/ED531546.pdf

		Halkoaho A, Matveinen M, Leinonen V, Luoto K, Keränen T., 2013. Education of research ethics for clinical investigators with Moodle tool. BMC Med Ethics. 2013;14:53. Published 2Dec 12, 2013. Retrieved Nov. 5, 2019 from: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867673/

 is Head of Clinical Operations, both from Clinical Research Malaysia

Survey results from Clinical Research Malaysia’s GCP refresher workshop.

Is Retraining on Good Clinical Practice Guidelines Effective?

	The International Conference on Harmonization-Good Clinical Practice (ICH-GCP) is an international ethical and scientific quality standard that ensures the rights, safety and well-being of clinical trial subjects are protected and that the clinical trial data generated are credible.

	Malaysia GCP Guideline was developed by National Pharmaceutical Regulatory Agency (NPRA) in 1999. This guideline adopts the basic principles outlined by ICH-GCP with some modifications to adapt to local conditions.

The object of the Malaysia GCP Guideline is to ensure that drug-related trials in Malaysia are conducted in accordance with international ethical and scientific standards.

 Although there is currently no legislative requirement for GCP training, mechanisms were in place to ensure that investigators are trained on GCP. For example, it is mandatory to submit a copy of Principal Investigator’s GCP certificate when obtaining regulatory approval from NPRA to conduct a clinical trial.

 In addition, all investigators must submit their GCP certificates for ethics committee’s approval in Malaysia.

 Since the first edition of Malaysian GCP to the current 4th edition, approximately 12,000 clinicians have been GCP certified.

	It is recommended for GCP certified personnel to be retrained on GCP guidelines every three years in order to stay up to date with updated regulations, standards, and guidelines.

 With this, Clinical Research Malaysia (CRM), a research organization founded by Malaysia Ministry of Health (MOH), has taken the initiative to conduct GCP Refresher Workshop for clinicians, nurses, allied health professionals and study coordinators who have been certified with Malaysian GCP. The objective of the workshop was to provide a review on the principles of GCP, to improve participants’ skills and knowledge on managing the conduct of a clinical trial, as well as to share recommendations on how to conduct a GCP-compliant clinical trial. 

	Since the first workshop in October 4, 2016, CRM has conducted 31 GCP refresher workshops throughout Malaysia to approximately 450 participants at no cost. The majority of the participants are clinicians, nurses, allied health professionals from government hospitals who are involved in clinical trials. Over the course of the conduct of the workshop, modifications have been made based on participants’ feedback to improve the quality and the learning outcome of the workshop. A summary of the changes in the workshop agenda is listed in Table 1.

Table 1: Changes in presented topics from 2016 to present

	As shown in Table 1, pre- and post- workshop assessment test was introduced in March 16, 2017 in order to evaluate the effectiveness of the workshop on participants’ knowledge on GCP.

	In this paper, we analyzed the pre- and post- workshop assessment score for workshops conducted since March 16, 2017. 

	Before the start of the workshop, participants were required to complete 20 multiple-choice GCP-related questions (pre-workshop assessment). The questionnaires were then collected before the start of the workshop. After the workshop, participants are then required to complete the same set of questions (post-workshop assessment). Participants were given 30 minutes to complete the questionnaire. 

	The average score of the pre- and post- assessment results from participants of the same workshop will then be calculated. This will constitute one set of data point.  

	The average score of pre- and post- workshop assessment from each workshop conducted since the introduction of the assessment in March 16, 2017 were compiled. Of the 28 workshops conducted since then, five workshops’ data could not be retrieved, hence only 23 sets of data point were analyzed.

	The compiled average score of pre- and post- workshop were then compared using Microsoft Excel’s t-test assuming unequal variance to evaluate if there is any significant improvement in the average assessment score after the workshop.

	Table 2 shows the compiled data from 23 workshops. 420 participants completed the pre-workshop assessment, and 434 participants completed the post-workshop assessment. There is on average, 20% improvement in the assessment score before and after the workshop.  

Table 2: Compilation of the average pre- and post- workshop assessment score.  

assuming unequal variances comparing the pre- and post- workshop average scores.

	As shown in table 3, the p-value is less than 0.05, suggesting that there the improvement in the score is significant after participants attended the GCP Refresher Workshop. 

	Training of investigators and allied health professions involved in clinical trials on the regulations and standards that govern clinical trials is important to improve the quality of studies and ensure maximum safety for the study subjects. A survey amongst clinical researchers in Saudi Arabia on their ICH-GCP knowledge found that its poor understanding of investigator’s responsibilities on informed consent, and prompt reporting to the ethics committee.

 Hence, refreshing investigators’ awareness of their responsibilities could help to improves the performance of investigators in conducting clinical trials particularly in these important ethical aspects.

	The GCP refresher workshop conducted by CRM fulfills its objective to provide revision of the principles of GCP to participants, with more an average of 20% improvement in assessment score after the workshop. 

	The factors that potentially contribute to the success of the CRM GCP Refresher workshop in improving participant’s score was discussed below:

	Case studies were included for “Informed Consent”, “Adverse Event Reporting” and “Protocol Deviations” for discussion. Participants were given real-life scenario case studies and they were required to answer guided questions in groups. Study have shown that case studies are more effective than textbook reading at promoting learning of key concepts and comprehension of the relevance of concepts to real life scenario.

	Several methods were used to make the workshop interactive such as games, quizzes, videos, group activities and group discussion. Active engagement of participants helps in the retain of information.

	Trainers would also actively engage participants by asking questions and encouraging participants to share their experience and practices. Regulations of clinical research can be understood more easily when participants can reflect the principles upon their own experience.

	Participants were given evaluation forms at the end of the workshop to provide their feedback and opinion of the workshop. Based on their feedback, modifications were made to improve the conduct of the workshop: 


		The first GCP Refresher Workshop is a half-day (4 hours) workshop. Participants reflected that the workshop felt rushed and suggested to make it a full-day course. Subsequent workshops were then conducted one full day (8 hours) to ensure participants can learn at a better pace, contributing a better learning outcome. 


		One of the earlier feed-back received is to include more activities especially for safety reporting and protocol deviations. Modifications based on this feedback is the shift from a lecture-style workshop to activity-based workshop. Presentation slides were also revised to be more concise to retain attention. 


		Following a feedback from participants, the current edition of the Malaysian GCP Guideline booklets were provided for participants to refer to during the workshop. 

	It is important for investigators and allied health professions who are involved in clinical studies to be trained on the latest GCP guideline. The GCP Refresher Workshop conducted by CRM is effective in refreshing participants’ knowledge on the GCP guideline. The success of the workshop could be attributed to providing case studies for discussion, interactive activities as well as taking participants’ feedbacks into consideration. We would recommend other governing bodies to support the conduct of similar interactive workshops in their jurisdiction; and to take participants’ feedback for continuous improvement. 

 is the Head of Clinical Operations, both of Clinical Research Malaysia.

		Good Clinical Practice Network, n.d. ICH GCP Good Clinical Practice. Retrieved 05Nov2019 from: 

		National Pharmaceutical Regulatory Agency, 2018. Malaysian Guideline for Good Clinical Practice 4th Edition. Introduction to Malaysian Guidelines For GCP, Page 8. 	

		National Pharmaceutical Regulatory Agency, 2017. Malaysian Guideline for Application of Clinical Trial Import Licence and Clinical Trial Exemption. Retrieved 05Nov2019 from: 

		Society Of Clinical Research Professionals Malaysia, 2016. A Guide to Conducting Clinical Trials in Malaysia, First Edition. Retrieved 05Nov2019 from: 

		National Pharmaceutical Regulatory Agency, 2018. Malaysian Guideline for Good Clinical Practice 4th Edition. Forward to the Fourth Edition, Page 4. 	

, n.d. Good Clinical Practice Training. Retrieved 05Nov2019 from: 

		Al-Nomay NS, 2015. Compliance with ICH-GCP Guidelines among the Saudi Health Care Professionals: Should Saudi Arabia Conduct Widespread ICH-GCP Training? J Public Health Dev Ctries. 2015; 1(2): 75-82. Retrieved 05Nov2019 from: 

		Bonney KM, 2015. Case study teaching method improves student performance and perceptions of learning gains. J Microbiol Biol Educ. 2015;16(1):21–28. Retrieved 05Nov2019 from: 

		Robin L. Bachelor Patrick M. Vaughan Connie M. Wall, 2012. Exploring the Effects of Active Learning on Retaining Essential Concepts in Secondary and Junior High Classrooms. Retrieved 05Nov2019 from: 

		Halkoaho A, Matveinen M, Leinonen V, Luoto K, Keränen T., 2013. Education of research ethics for clinical investigators with Moodle tool. BMC Med Ethics. 2013;14:53. Published 2013 Dec 12. Retrieved 05Nov2019 from: 

Yoong Kai Shen and Joanne Yeoh, both of Clinical Research Malaysia, analyze the pre- and post- workshop assessment score for GCP workshops conducted since 16 March 2017. 

Joanne Yeoh

Articles

The ICR-CRM-IQVIA Research Network Collaboration Experience

Is Retraining on Good Clinical Practice Guidelines Effective?

Is GCP Refresher Training Effective—Perspective from Malaysia