Decentralized clinical trials (DCTs) offer many advantages to patients, sites, and sponsors, particularly under circumstances such as those experienced during the COVID-19 pandemic, when on-site visits were restricted. In the Asia-Pacific region, there has been significant interest in DCTs, but adoption has not yet reached the levels seen in the United States.
In Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) is promoting DCTs, and the Ministry of Health, Labour, and Welfare (MHLW) will release guidance and take some actions in Q1 2023. Although there has been only limited use of DCT components, such as e-Consent, eCOA, and home healthcare to date, the MHLW guidance is expected to help further promote DCTs.
Movement toward DCTs is greater in China following the rapid spread of COVID-19 in the first half of 2022, which resulted in the lockdown of numerous cities, including Shanghai. During this time, regulators in China strongly encouraged all sites and sponsors to adopt DCTs. Many trial sponsors deployed DCT solutions to enable the continued success of their clinical trials, particularly those pharma companies with valuable experience with DCTs in Western countries. Additionally, China has seen significant advances in IT technology in recent years, facilitating remote interactions among all residents. In many hospitals, doctors are able to treat patients remotely via telemedicine, which provides a good foundation to drive the adoption of DCT solutions. With more and more global studies being designed using DCT models, China has been increasingly involved in DCT trials, particularly among the top tier of clinical trials sites.
Singapore is a small island country with excellent healthcare infrastructure and where most people can easily travel from home to the hospital. As a result, technology-based solutions, such as eCOA and ePRO, have been more popular compared with eConsent and home healthcare. However, as patients become more aware of the option to fit their work and life schedules in around clinical trial requirements, it is likely that DCTs will become more prevalent.
In general, the APAC region is conservative and highly cost sensitive. The DCT paradigm is fairly new, and as a result there is hesitancy owing to a lack of knowledge on how to effectively and ethically implement decentralized trials. The cost and time involved in initially developing and implementing DCT solutions are also causes for concern. Often, the decision is made to stick with established, paper-based activities and on-site visits for fear of introducing new methods. More education and training are required, along with the successful implementation of “case study” trials to help demonstrate the benefits of DCTs with respect to the enhancement of study efficiency and patient satisfaction. Such case studies exist outside the Asia region of APAC (i.e., Australia and New Zealand) with proven benefits and success. Our challenge, therefore, is to replicate these success stories in Asia for a more relatable example based on their local healthcare experience.
The APAC region is conservative and highly cost sensitive. The DCT paradigm is fairly new, and as a result there is hesitancy owing to a lack of knowledge on how to effectively and ethically implement decentralized trials. The cost and time involved in initially developing and implement-ing DCT solutions are also causes for concern.
With the DCT model so recently introduced to the APAC region, there are no strong regulations in place or “hard and fast” rules set out by the regulators or governments in these countries that provide clear instructions on what can and cannot be done. Investigator sites have been left to make the choice to pursue or ignore DCT approaches according to the specific cultural biases that exist in each country. On the other hand, vague rules around DCTs have also propelled innovative companies to explore new ways of conducting trials without fear of reprimand.
For example, for oncology patients, Chinese doctors and patients prefer face-to-face rather than virtual visits. Based on recent studies deployed in Japan, sites are central to promoting home healthcare to patients. Once the PI is comfortable deploying home healthcare, patients can meet the home healthcare nurses during a site visit and formal introductions can be made by the site team, thereby increasing patient confidence. On the other hand, the Japanese people are keen on technology and quite ready to adopt wearables and other digital solutions, such as e-Consent.
China is different from most other APAC countries owing to its very large size. The level of understanding and acceptance of DCTs by sites and patients varies from region to region within the country. In some areas, there is extensive training and education and thus a higher acceptance of DCT solutions, including home nursing. In other parts of the country, participation in even traditional clinical trials is very low. However, large pharma companies are increasingly targeting China for their first approvals, owing to a reduction in the time needed to reach NDA approval in China in recent years.
Recent regulatory guidance issued in the wake of the COVID-19 pandemic has begun to have a positive effect, however, with more investigator sites interested in moving ahead with DCT solutions. Sponsors remain hesitant, due to a lack of clarity about whether decentralized trials will be accepted by regulatory authorities. International sponsors are particularly concerned, given that there are so many differences from country to country. For instance, there is different Internet infrastructure in China, and a law regarding confidential data collection that requires the use of a local server took effect in November 2021.
There are also other, more fundamental challenges to setting up DCTs in China and onboarding global vendors. While most people in Western countries have e-mail addresses, a much smaller percentage of Chinese citizens do. The significant differences in digital communication infrastructure and privacy regulations compared with Western countries is a key issue, and significant upgrades to digital platforms are necessary before DCTs can be widely implemented in China.
With the DCT model so recently introduced to the APAC region, there are no strong regulations in place or “hard and fast” rules set out by the regulators or governments in these countries that provide clear instructions on what can and cannot be done.
A general challenge to DCTs in APAC will be the willingness of patients to accept home healthcare. While the use of wearables can dramatically reduce the amount of data requiring in-person visits to monitor, there will always be key elements that cannot be evaluated remotely. For a trial to be completely decentralized, a physician or nurse must meet with the patient at his/her home. In addition, home health visits provide reassurance to patients and give them confidence that a clinical professional will be assessing them in person in a familiar, face-to-face fashion.
Interest in home nursing may actually be higher than might be expected. Patients in China currently participating in traditional trials run by PPD were surveyed about DCTs, and, surprisingly, four in five indicated that they would accept home nursing.
As is the case with DCTs in the United States and Europe, there is an expectation that offering patients the option to have fewer site visits will provide more patients in remote locations the ability to participate in clinical trials. Both recruitment and retention are expected to increase because of remote solutions and the significant reduction of patient burden with respect to site visits, but those benefits will not manifest until it has become possible to overcome the cultural hurdles limiting deployment.
As a global organization with experience conducting decentralized trials in the United States and Europe, PPD is well positioned to help educate sponsors and investigator sites in the APAC region regarding the benefits of DCTs. The digital and decentralized solutions team at PPD locations in Asia are staffed with subject matter experts that can help with the implementation of individual digital solutions, as well as hybrid and fully decentralized trials, across APAC countries. We also have a network of technology vendors that have extensive knowledge about their DCT solutions.
Sponsors that wish to conduct DCTs in APAC countries should specifically stipulate such expectations in their trial protocols, as sites are more likely to adopt DCT solutions if sponsors make it clear that they are supportive. Consideration of the positions of regulatory authorities and the potential impacts that DCTs may have on investigator revenues is equally important.
For those sponsors not yet sure about DCTs, the key is to start small and introduce them to the benefits of DCTs one step at a time. PPD is building a network of sites across the APAC region that are interested in implementing DCTs. These sites are waiting eagerly to participate in DCT pilot studies and serve as a bridge to the wider adoption of DCT solutions. Once more studies have been completed at these sites, sufficient data will be available to convince other sites and sponsors about the value of DCTs in APAC.
Even for studies in China, PPD runs a global, uniform platform. Many other CROs use a separate platform in China to reduce regulatory requirements, but that means that the data are completely separate. PPD believes that the additional work required to use a global platform is worthwhile, because it enables all trial data to be collected in a single, universal system, facilitating data sharing and analysis.
The resistance to DCTs that exists in APAC countries is driven more by apprehension of the unknown than any specific aversion to the concept of decentralized trials. Investigator sites and patients in the region are highly interested in advanced technologies. They understand the potential benefits of DCTs for sponsors, sites, and patients and are interested in moving in that direction where possible.
However, they are first seeking more proof concerning how DCTs can be successfully implemented in the region. They want to see concrete evidence from more “case study” trials in Asian countries and to learn more about the experiences that Western sponsors and investigator sites have had with DCTs. In particular, they want to know what challenges had to be overcome and how that was achieved, so they can avoid the same issues.
Most countries in the APAC region are at the forefront of technology and recognize that DCTs, which are made possible by advances in digital capabilities, are an important trend that will likely replace more traditional clinical trial models within the next five years or so. As we move to more DCT visits, there will always be an element of centralization required, hence early engagement with sites is a crucial bridge to enabling DCTs globally. As CROs like PPD help people better understand the various aspects of DCTs and become more comfortable with how they can be successfully implemented, including home healthcare solutions, the rate of adoption will increase.
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