As coronavirus disrupts MNC operations in China, companies look to digital solutions
Biopharma will need to turn to digital solutions in China in the face of the coronavirus crisis
The coronavirus outbreak in China has triggered a stark call to action across the international biopharma community to treat, diagnose and prevent the spread of the virus, but it has also revealed some cracks in China's infrastructure that have upended clinical and commercial operations in the region. The resulting crisis may ultimately push MNCs, Chinese biopharmas and regulators to accelerate adoption of digital trial monitoring and marketing tools, and decentralization of trial sites, in order to avoid similar issues in the future.
For MNCs and Chinese biopharmas, one of the biggest operational impacts of the crisis will be on clinical trials. Healthcare resources are being diverted to address the epidemic and patient visits to hospitals are restricted to prevent the spread of disease.
CROs are reporting disruptions to normal clinical trials, with new trial starts and new patient enrollments in ongoing trials coming to a halt. In some cases, enrolled patients are facing challenges accessing their therapies and seeking scheduled evaluations (see “China Faces Clinical Delays”).
“Except the clinical trials of anti-coronavirus drugs and vaccines, study start-up activities have stopped in most hospitals,” said Yan Yi, head of clinical and commercial operations at CRO dMed Biopharmaceutical Co. Ltd.
“If you want to start a trial at a new site, that’s almost impossible. Travel has almost stopped and you can’t move from city to city.”
The high concentration of clinical trial sites in relatively few regions is exacerbating the problem. The limited infrastructure for digital trial monitoring is exposing a weakness, as it means that remote monitoring systems can’t be a fallback option.
“If you want to start a trial at a new site, that’s almost impossible. Travel has almost stopped and you can’t move from city to city. Hospital visitation has gone down to almost none and companies have to rely on telecommunications,” said Jun Bao, president and CEO of Chinese cancer company Impact Therapeutics Inc.
MNCs often run clinical trials at a few major academic research hospitals in China, making them vulnerable to major disruptions.
According to a Lancet study from last year surveying 851 oncology trials in China, trials were mostly concentrated at just six sites. Dan Zhang, executive chairman of CRO Fountain Medical Development Ltd., told BioCentury, “We are seeing the virus spreading out from Wuhan, where it started. In addition to Wuhan, study sites located in major metropolitan areas will also be impacted, for sure."
BioCentury’s survey of MNC trial sites in China shows a large overlap between where 2019-nCoV cases are being recorded and where companies are running their trials, suggesting many trial sites could be negatively impacted (see Figure: "Mapping Coronavirus").
Figure: Mapping coronavirus
Of the 31,211 cases of coronavirus in China reported to WHO as of Feb. 7, over two-thirds -- 22,112 cases -- are in Hubei province, where the virus was was first identified in capital city Wuhan. Other cases of the virus are concentrated in the surrounding provinces, while clinical trial sites are most heavily clustered in Beijing and Shanghai.
The top map shows coronavirus cases reported to WHO as of Feb. 7. The bottom map shows trial sites for interventional clinical trials listed as recruiting or active in ClinicalTrials.gov as of Feb. 4. Trials with multiple sites in the same province are only counted once in each province. WHO lists Taiwan as "Taipei" in its report, which is reflected here. Source: WHO, ClinicalTrials.gov
Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus. The 2019n-CoV content is free to all who visit the site.
Some MNCs will feel the brunt more than others. For example, one-third of the clinical trials sponsored by Roche (SIX:ROG; OTCQX:RHHBY) have a site in China, and 17% of those are being run through the virus’ epicenter in Wuhan (see Figure: “MNC Trials in China”).
Figure: MNC trials in China
At least 18 biopharma MNCs are conducting clinical trials in Wuhan. BioCentury searched ClinicalTrials.gov for interventional trials sponsored by biopharma MNCs with sites in China. Shown below are the number of trials in Wuhan and elsewhere in China (bars, left axis) and the percentage of each company's worldwide trials with at least one site in China (lines, right axis). Roche includes trials sponsored by Genentech. Bristol-Myers Squibb includes trials sponsored by Celgene. Trials sponsored by multiple companies are counted for each sponsor. Source: ClinicalTrials.gov
MNCs could also take a hit on top-line growth in China as travel restrictions limit drug access and disrupt marketing, which still heavily relies on in-hospital, face-to-face sales.
Even before the crisis hit, there was a push toward digital marketing in China, but the outbreak brings more urgency. Implementing digital technologies such as remote monitoring systems for clinical trials could be crucial for helping biopharma companies and regulators get through this crisis; it should certainly be on the table as a step to shield them from similar disruptions in the future.
Meanwhile, hospitals are implementing short-term fixes such as prioritizing the most urgent trials to address current disruptions.
Zhang and dMed's George Baeder both think a long-term effect of the outbreak for the biopharma industry will be a rapid acceleration of the deployment of digital tools that allow for at-home monitoring.
Baeder is SVP of strategy and business development at dMed.
“People are beginning to talk about remote and centralizing monitoring. With the current ongoing infectious disease spreading, we may begin to consider using these technologies to reduce the necessity of on-site visits,” said Zhang.
Remote monitoring tools include clinical trial management systems (CTMS) and electronic data collection (EDC) systems.
Zhang noted that the U.S., EU and Japan already accept remote monitoring, but China hasn’t officially endorsed the process in new guidelines. He expects that will soon change.
“People with site-level EDCs are in better shape to manage the current situation.”
According to Baeder, dMed is already using an EDC system to monitor patients. “Although paperless EDC systems are not used in all China trials, people with site-level EDCs are in better shape to manage the current situation.”
He added, “The concept of virtual trials is not clearly defined, but approaches that allow you to monitor patients remotely have become increasingly valuable in accelerating recruiting and lowering trial costs."
Situations that limit travel and hospital visits are another reason to make such systems a priority.
The coronavirus crisis may also be the push that Chinese CROs and sponsor companies need to branch out from the established set of clinical trial centers they use, as it would minimize exposure to crises in the future.
New legislation that lifts restrictions on trial sites also makes it a good time to do this (see “Growing China’s Capacity to Conduct High-Quality Trials”).
“It’s really a natural time to decentralize the location of medical centers for conducting trials in China, and this would help in these types of infectious disease situations in the future,” said Zhang.
“We would definitely entertain doing trials at more sites than we’re currently using. There are enrollment pressures, especially for certain rare diseases, and we want to be able to reach patients at more sites,” he added.
“In addition to Wuhan, study sites located in major metropolitan areas will also be impacted.”
In the past, global trials in China were restricted to certain pre-qualified sites, which is one of the reasons that multinationals tend to center on major academic institutions in big cities.
Under the new Drug Administration Law passed last year, those restrictions have been lifted and pre-qualification is no longer required.
Baeder agreed that site selection and management is an important strategy for multinationals and CROs in China moving forward, and one of the keys when branching out is establishing trial infrastructure at new hospitals.
“Often, companies tend to go where they can get sites signed up quickly and easily, with limited effort by the CRO or sponsor to build infrastructure in those hospitals,” he said.
While CROs can own clinical trial sites in the U.S. to create that kind of dedicated infrastructure, that isn’t possible in China.
Developing longer-term relationships with hospitals to create the kinds of set-ups necessary for particular therapeutic areas is a good step, and one that dMed is taking for clients, Baeder said.
Digital technologies also have the potential to solve a commercial challenge in China that has been brought to light during the coronavirus crisis -- the heavy reliance on representative site visits.
“The frequency and number of rep visits to hospitals are typically the single biggest variable in determining sales success. In the last five to six years, companies have tried to move toward other forms of digital communication, but in-person interactions are still a hugely important part of the sales process in China,” said Baeder.
“My guess is that because hospitals are telling people not to come and cities are telling people not to travel, we will see a dramatic decline in sales calls,” he added. “This is likely to be reflected in sales of drugs fairly immediately.”
“Companies with strong digital marketing and promotion tools in place have a real differentiator.”
Zhang told BioCentury there had already been a push to move sales teams in a digital direction before the outbreak.
“Even before the disease made business more difficult, hospitals began to limit pure sales activities, unless they include medical education efforts,” he said.
Baeder added, “Companies with strong digital marketing and promotion tools in place have a real differentiator. They will be better off now than those that rely exclusively on traditional rep-based approaches.
Shifting guidelines for clinical development
Hospitals and companies are navigating the operational disruptions by relying on telecommunications and the digital infrastructure that’s already in place, and by prioritizing trials for severe diseases.
Hospitals are setting individual guidelines for trial prioritization. According to Impact's Bao, a Shanghai hospital where Impact is running its trials is still taking new cancer patients. “But for other chronic diseases like cardiovascular diseases, they are not taking new patients at this time and are dissuading the patients from coming to the hospital.”
At the national level, the centralized government also issued guidelines for clinical trial management during the crisis based for the Requirements for Prevention and Control of Hindering Abrupt Contagion announced by the National Health Commission. The guidelines, titled “Consensus on the management of clinical trials under the primary response to major public health emergencies (infectious diseases),” were issued by the Clinical Research Capacity Building and Human Research Participants Protection (CCHRPP).
That provides clear guidance on how to manage clinical trials under the current special situation, such as remote and centralized monitoring, alternative approaches for necessary examination and testing, investigational medication distribution and adverse event reporting, said Yi.
Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus. The 2019nCoV content is free to all who visit the site.