Findings from a recent Economist Intelligence Unit (EIU) report¹ indicate that the use of patient-centric clinical trials-that is, trials that are designed and conducted with the patient perspective in mind-can accelerate enrollment, increase the likelihood of drug launch, and ultimately facilitate inclusion in payer formularies. Yet, patient-centric trials have not been widely adopted (they represent only 5.2% of Phase II and Phase III clinical trials conducted globally from 2012-2017), and adoption rates are particularly low in China.¹

In China in particular, there is a significant opportunity to expand the use of patient-centric trials. The Chinese clinical research market is growing thanks to regulatory reform, the Government’s interest in healthcare and patient demand for better medical care and medicines. Patient centricity in clinical trials may help support innovation and the introduction of novel medicines to the Chinese market and to patients who need them.

Focused on the development of innovative new therapies to improve the world’s health, Parexel recently organized a roundtable discussion in Shanghai on patient-centric approaches and how various stakeholders can more effectively bring the patient into the drug development process. Participants from pharmaceutical and biotech companies, hospitals, a government agency, a research institute, and a patient advocacy group (PAG) discussed topics that included policy, culture, processes, technology, and other enablers of patient-centric clinical trials.

This article illustrates both the opportunities and the challenges surrounding patient centricity and patient-centric trials in China based on this roundtable discussion and related considerations, including Parexel’s own experience.

What is patient centricity?

There is no universally accepted definition of patient centricity, though most sponsors describe it in terms of putting the patient at the heart or center of clinical research.  The EIU report defines a “patient-centric trial” as one that involves patients in its design and execution. ¹ The ultimate aim of a patient-centric trial is to make it as easy as possible for patients to learn about and participate in clinical trials by reducing barriers, and to generate clinical data that reflect the real needs of patients and not only those perceived by doctors and pharmaceutical companies. In turn, this can have a positive impact on recruitment, retention, patient experience, compliance, and, therefore, budget and timelines.

Around the globe, experience with patient-centric trials is growing. Adoption of these innovative trials, however, is still in its infancy. Today, 38% of patient-centric trials are conducted in the US, while 34% are performed in the EU. In China, just 5% of trials are patient-centric.¹ While barriers remain, enabling factors also exist to improve adoption.

Two case studies illustrate how sponsors are overcoming barriers to adoption across the globe.  

Case study 1: Phase II, Serious Neuropsychiatric Condition (Parexel, data on file)

Situation

The sponsor wanted to take a patient-centric perspective on protocol design by eliciting feedback from patients and caregivers. The sponsor was faced with two options:

a) A 12-month study with a compulsory lumbar puncture (LP)-resulting in a lower visit burden, but with an uncomfortable procedure.

Or

b) An 18-month study with a choice for sites between LP and PET scan-the result being a higher visit burden but with the potential to avoid the difficult procedure and with an option for a 12-month extension study if the drug was efficacious.

Challenge

The sponsor was uncertain on which approach was preferable to patients to ensure compliance with the protocol.

Solution

Parexel deployed Patient Centric Protocol Optimization (PCPO) methodology and found that

patients, caregivers, and site staff overwhelmingly preferred the longer duration study with the higher visit burden, in order to avoid the difficult procedure and the subsequent stress and anxiety that it would cause in this vulnerable population, in addition to the potential to participate in the extension study. The sponsor was, therefore, able to make an informed choice about its final protocol to ensure a truly patient-centric approach.

Case study 2: Phase III, Serious Pediatric Neurological Condition (Parexel, data on file)

Situation

The study was designed to explore a possible treatment for very young children with a serious neurological condition. Our client was asked by the FDA to include in their protocol design a requirement for three 48-hour or 72-hour videos of EEG monitoring in the hospital.

Challenge

The sponsor was concerned that recruitment of patients into the trial would be unachievable due to the time commitment required from parents and their children.

Solution

Parexel deployed two of the four possible elements of the PCPO service:

• One was a caregiver survey, which identified and directly surveyed parents of eligible children to understand the current burden of treatment, their potential interest in a clinical trial, and the possible impact of 72-hour video EEG monitoring.

• The other was a Patient Burden Analysis (PBA), which surveyed expert nurses who were asked to provide feedback on the study design.

Surprisingly, the caregiver and PBA surveys showed that the visit burden was in line with the standard of care for patients. The majority were hospitalized around three times per year for approximately three days at a time.

An unexpected finding was that the highest barrier to participation cited by the majority of parents was lack of childcare for their other children while they stayed with their participating child for longer visits.

As a result, the sponsor was given recommendations to help sites overcome the childcare situation as part of their recruitment and retention plan, such as on-site childcare facilities and scheduling these longer visits on weekends.

Patient-centric trials in China: Current situation and challenges

The Roundtable panelists identified several challenges in China during the discussions, such as workforce unreadiness, lack adequate clinical information and support for patients and PAGs, and a weak infrastructure with fragmented data.

Workforce readiness:

Lack of information and training: In China, healthcare practitioners (HCPs) are currently less informed about clinical trial operations and protocol design. Today, only around 800 hospitals in China are GCP-certified to execute clinical trials,²  out of 29,000 hospitals in total (as of the end of October 2016).⁶  This figure presents an opportunity to focus on these hospitals as early adopters of patient centricity.

Lack of time for proper communication: Outpatient doctors are generally very busy in China, especially in tertiary hospitals. Compared to developed countries such as Australia, which has 1.55 general practitioners per 1,000 people; in China, this number is only 0.1⁷-more than a 15-fold difference. Additionally, patients, especially those at a lower educational level, have a hard time understanding medical jargon, which can lead to challenges in communicating about clinical trials.

One panelist mentioned that, due to lack of time, even if doctors try their best, they may not have a thorough understanding of a patient’s condition in just one visit. They might not be able to provide the best trial options for their patients, especially if this requires additional research on the doctors’ part. This will also pose a big challenge in managing patients’ expectations of the experimental treatment.

Patients and PAGs lack information and support

The roundtable discussion surfaced several important considerations that are specific to China with regard to patients and their advocates, who have very limited access to information. Some patients in rural areas don’t even have basic information on their disease and treatment, which can make them vulnerable to misinformation.

Infrastructure/fragmented data

Healthcare data are fragmented and exist in different forms and systems, in China as well as in other countries. In China, health services and IT integration is pretty low. ⁸ Accessing such data is difficult even within the same system. A roundtable panelist cited an example regarding a hospital health alliance. The system in a leading tertiary hospital has stored data for all patients in the alliance, but an individual doctor does not store the data. If doctors want to access the data, they need support from the IT department; this is not efficient and can lead to more work for the doctor.

How to make patient-centric trials a reality in China

In addition to the challenges, roundtable participants also discussed different ways to achieve better patient centricity in China. Some ideas include empowerment, collaboration, and technology advancement.

Empowerment

• Patient empowerment–
• Medical jargon, such as the ones in medicine brochures or consensus forms, should be translated into a simple language to facilitate patient understanding. Note that empowering should include not only patients but also the family, since the decision to participate in a clinical trial can be a family issue. This could be overcome in part by utilizing literacy and health literacy guidelines when developing educational materials for patients, or even using video in the local language to explain trial details, so that reading ability is not a barrier to understanding.

• Making clinical trial information available on WeChat, a mobile app that is widely used in China, could further enhance access to information about clinical trial opportunities.

• There is also huge interest from Chinese patients and advocates in seeing study results. An appropriate approach is needed to deliver results to patients, since the data can be sensitive and personal. Lay summaries, from a simple one-page letter, through to a magazine article written in lay language, can be a valuable tool to provide information back to patients in a digestible format. The National Medical Products Administration (NMPA) may also consider following the European Medicines Agency’s (EMA) lead and making this step a requirement to ensure adoption.

• PAG empowerment –
• In China, PAGs appear to be very interested in patient-centric trials and encourage sponsors to contact patients as early as possible. Since PAGs in China are still at an early stage of development, funding may help them operate more systematically and strategically.

• Sharing information and training PAGs on effective communications with key industry stakeholders may also be beneficial. Implementation of a training program, similar to the EU’s EUPATI, which creates patient experts in clinical research and offers a toolbox of simple educational materials, could be a route to follow in China. EUPATI was part-funded by the EU, so taking a similar approach and seeking Chinese government support could be considered.

• Physician empowerment –
• The perception of physicians is fundamental to the success of a clinical trial. Training related to clinical trials should include as many physicians as possible in China; those not conducting trials should be educated as potential referral sources for patient recruitment into trials. In December 2018, in collaboration with Eli Lilly in China, Parexel rolled out a training program to sharpen the skills of Chinese physicians and better equip hospitals for clinical research.⁵ This is an important and meaningful first step.

• On an individual study basis, conducting investigator meetings locally, in Chinese, is also an important way of educating and securing engagement in clinical research. Additional investment from sponsors and CROs in China could help overcome this barrier by working on summarizing study information for site staff and disseminating it in a quickly digestible format. 

• Site management organizations (SMOs), whose primary responsibility is to support investigators participating in a clinical trial, can also provide excellent opportunities in China. It may be beneficial to employ SMOs for multicenter and multinational trials that give rise to more challenges for recruitment, ethics committee document submission and approval follow-up, and data entry support. Done right, SMOs can decrease clinical trial costs and help trials run more smoothly. Collaborations with hospital health alliances can also potentially help with recruitment in clinical trials.

Collaboration

Early involvement of regulators, sponsors, physicians, and patients is essential to the successful execution of patient-centric trials in China, and indeed in many other countries. All parties should be engaged early on to build consensus on patient-centric endpoints and trial designs. Protocol flexibility should also be increased so that patient feedback can be included and the protocol can be optimized with the patient’s interest in mind. All parties, including investigators, should be sensitive to patients’ benefits and burdens, and keep patient centricity in mind during all stages of clinical development. They should be particularly mindful to ensure that clinical endpoints are meaningful to patients. Pharmaceutical companies and CROs should ensure patient access to information about clinical trials so that eligible patients are aware of available trials and may be recruited at the right time. CROs can help promote a better understanding of patient-centric trials for the benefit of all stakeholders. Conducting pilot patient-centric trials and then sharing methods and results with the NMPA may be very helpful in accelerating adoption. Bottom-up support from patients and PAGs will also help draw interest in patient centricity.

To overcome the challenge of data protection, technical specialists in the IT department of a hospital can take the lead to arrange ethical data access. They can also work on creating an electronic medical record (EMR) approach that is more unified and easier to integrate across hospital systems in China. This would be an excellent opportunity for a local startup company or experienced EMR vendor to work in this space to help overcome this particular challenge in China.

Technology

Technology has the potential to underpin the future of clinical trials and can help execute patient-centric trials. This can range from providing simple mobile apps that deliver education and visit reminders to study participants, and to the deployment of virtual trials (also sometimes called “remote”, “siteless” or “decentralized” trials, though the pharmaceutical industry is yet to agree on preferred terminology).

Roundtable participants discussed the benefits of virtual trials. Such trials are designed to make it as easy as possible for patients to participate in clinical research by taking all or part of the study to them in their homes. Many patients may have a great interest in participation but are unable to enroll due to factors such as:

• Geographical barriers, e.g., living too far from the site or having no transport available

• Financial barriers, e.g., unable to afford time off work

• Practical barriers, e.g., lack of childcare or no caregiver available to accompany them to visits

These participant challenges can also have a huge impact on recruitment and retention, a challenge that the industry has been experiencing for some time. A virtual approach uses technology like mobile apps or wearable devices to help overcome practical challenges to participation, often in addition to home nursing and telemedicine, thus potentially increasing enrollment. However, overall there is a need to explain the nature and potential benefits of virtual trials to HCPs and patients, in addition to adopting virtual trial methodology to meet the cultural and technology needs of these stakeholders.

Conclusion

Patient-centric trials are receiving more attention and interest across the EU and US, but are still not widely adopted there or in China.¹ Since China has a vast population and large unmet medical needs, there is a significant opportunity for patient-centric trials to succeed. While there is a need to educate all stakeholders about the potential benefits and operational details of patient-centric trials, education, collaboration, and empowerment are the first steps toward success not only for patient-centric trials, but more broadly for drug development and healthcare in China. Taking a patient-centric approach is not only the right thing to do but, as the EIU report shows, delivers tangible business benefits as well as the ability to get new medicines to patients faster. It is no longer a “nice to have”-it is a research and business imperative.

Rosamund Round, Director, Patient Innovation Center, Parexel; Victor Cheng, Vice President, Technical, Parexel Consulting; George Lee, Vice President, Clinical Operations and Country Leader, China, Alberto Grignolo, Corporate Vice President, Parexel Consulting; and Sy Pretorius, Executive Vice President, Chief Medical & Scientific Officer, Parexel

The authors are deeply grateful to Jiaxin Chen and Amanda Mao for their thoughtful and diligent research and writing support during the drafting and completion of this article.

References

• The Innovation Imperative: The Future Of Drug Development. ©2018 The Economist Intelligence Unit Ltd. All rights reserved. https://druginnovation.eiu.com. Accessed March 11, 2019

• List of drug clinical trial institutions. China National Medical Products Administration. http://app1.sfda.gov.cn/datasearchcnda/face3/dir.html#maodian1 (in Chinese). Accessed March 11, 2019

• Sun, A. How China's innovative drug research and development has fallen at the most critical moment? https://www.36kr.com/p/5165613 (in Chinese). Accessed March 11, 2019

• Wenzel, K. Possibilities and Requirements for the Use of Connected Sensors in Clinical Trials. CR pro. 2017 (4): 14-17

• Eli Lilly China and PAREXEL join hands to focus on clinical research talent training to promote innovation and upgrading of China's biomedical industry. http://www.sohu.com/a/279251612_152537 (in Chinese). Accessed March 11, 2019

• Xu, W., et al. Research on the innovative drug access to the Drug Directory for National Basic Medical Insurance in China. http://wap.china-pharmacy.com/6/21/23539.html?ps=4 (in Chinese). Accessed April 25, 2019

• China sector analysis: Health care. https://seekingalpha.com/article/4258126-china-sector-analysis-health-care. Accessed May 10, 2019

• Tertiary hospitals speed up expanding, exposing fragmentation issues of the health care system. https://www.iyiou.com/p/62412.html (in Chinese). Accessed May 10, 2019