Paul Bridges SVP Worldwide Head Regulatory & Access, Parexel and Sheela Hegde, Partner and Managing Director, Health Advances05.18.20
Amid the COVID-19 pandemic, it’s not easy to think about next year. The pharmaceutical industry is leading the charge to find therapies and develop vaccines, while simultaneously modifying existing trials to the new environment, and keeping their staff and patients safe. But the industry will be different after the crisis passes, and sponsors must prepare for it.
Some of those differences are already becoming clear. Few scientists doubt that the novel coronavirus will be the last to emerge. There will be more generous incentives for companies to invest in developing vaccines and infectious disease (ID) drugs. The public and policymakers will push for the accelerated development of new and affordable medicines, as the pandemic has shined a bright light on disturbing healthcare inequities. Accelerated development will demand more real-world evidence (RWE) – with concomitant greater transparency in industry-regulatory communications and relations – as well as adaptive and hybrid trials to make activities in all stages of development more parallel and less sequential. At the same time, trials will become more decentralized and patient-centric to increase convenience for enrollees.
There is a theme emerging in all these changes: a new pragmatism. The sooner companies can adapt, accelerate change, and plan for tomorrow’s challenges, the stronger their positions will be. And the better prepared they will be to continue creating and marketing new drugs for patients who need them.
What the new pragmatism will mean
In our daily lives, whatever we can do remotely, we’re now doing. In many instances, we’re discovering it is more efficient. The same will be true in drug development. Whatever can be done remotely, will be, and that may prove to be for the better.
Clinical trials: The rise of new tools and approaches
Due to limited (or no) access to clinical sites, many trials have been put on hold. But for many others, including some of those run by Parexel, sponsors and managers are transitioning to distributed trials with remote monitoring and source document verification (SDV) to ensure that participating patients can continue to benefit.
While COVID-19 occupies the world’s attention, there are still substantial public health challenges in oncology, heart disease, and many other major and rare conditions. Clinical research must continue. For it to do so, sponsors and CROs must maximize their creativity while staying aligned with regulators. Drawing on our experience in late-phase studies, Parexel has have implemented technologies and approaches— such as eConsent, wearables, telehealth, telemedicine, and remote SDV – for remote monitoring of Phase II and III studies.
For example, telemedicine was not widely reimbursed by many insurers, including Medicare, before the pandemic. Now it is, and that will likely continue. The limitations that slowed the adoption of mobile technologies in clinical trials, including concerns about excluding bad or missing data, user errors, and the lack of device validation, will fade as the incentive to overcome them becomes compelling. The feeling that these tools would be “nice to have someday” has become “we need it today.”
We are unlikely to return to the old ways of conducting clinical trials once we have discovered the benefits of these new tools for researchers, patients, and regulators. And sponsors that become adept at using them will prosper in the future.
Regulatory: An increase in responsibility
The lives of regulators have changed dramatically, as most now have to work from home. Meetings that once took place in person – EMA scientific consultations, FDA end-of-Phase 2 meetings, even FDA Advisory Committee meetings – are now being held remotely if they’re being held at all. Sponsors must think pragmatically and learn to live with this new reality, even if it’s less desirable, and make the most of their available interactions with regulators.
In the last six weeks, 50 of the world’s regulatory agencies have issued new guidance on how sponsors should manage ongoing clinical trials and launch new ones. This guidance illustrates new flexibility regarding clinical trial management. However, standards on GCP compliance have not been lowered, and all amendments, protocol deviations, and adverse events must be reported diligently. Regulations are critical to safe drug development; loosening them can put patients in harm’s way.
Regulators are allowing sponsors greater independence in how they maintain compliance during this emergency. But sponsors should still maintain GMP and GCP compliance as tightly as possible to protect their development plans, ensure ultimate regulatory approval, and preserve the lifecycle of their products on the market. They have to balance creativity in conducting and managing compliant clinical trials with the expectation that they will have to satisfy regulators’ expectations. Importantly, ICMRA and its 29-member agencies have called for the conduct of large, well-designed, and controlled clinical trials to address COVID-19. To answer this call, sponsors must push the envelope of pragmatism by setting aside their differences and collaborating for the common good.
Once sponsors and CROs master this new regulatory environment – which has the potential to create new efficiencies, shorten response times, and reduce costs – there will be little incentive – scientific, operational, or financial – to return to old ways of operating. That genie is out of the bottle.
GMP enforcement: Remote rigor
Today, manufacturing plants around the world in receipt of regulatory enforcement letters are trying to retool and remediate their operations to get back into compliance quickly and cost-effectively, calling on experts for help. But those experts cannot now travel to sites in India, South Korea and China, and who knows when they will be able to? International auditing guidelines allow for remote auditing; regulatory authorities are issuing guidance to better facilitate them during the pandemic; and experts and starting to direct and monitor remediation efforts remotely, using video, virtual reality, and other advanced tools.
In the future, we can expect that experts will spend less time on planes, less time navigating new environments, and more time working on problems. This will be better for patients, manufacturers, supply chain managers and regulators, and more cost-effective for everyone, including payers.
Major regulators have largely discontinued manufacturing plant inspections for the time being, or do what they can do remotely. But they have not lowered their expectations that plants must be GMP-compliant. Indeed, it’s not unreasonable to expect more scrutiny as supply chain disruptions increase the risk of GMP deviations. This is no time for manufacturers to relax their GMP focus and discipline.
Where investments will move
For many years now, funding for R&D in infectious disease treatments or vaccines has come mainly from government entities, such as the U.S. National Institute of Allergy and Infectious Diseases, and philanthropic organizations, including the Bill & Melinda Gates Foundation. The biopharma industry has invested its development dollars in other areas, and infectious disease programs currently represent less than 2 percent of the overall development pipeline. The COVID-19 pandemic has revealed the enormous danger (and cost) of not having vaccines to hand, and society may be ready to spend more on reimbursing and rewarding good drugs and vaccines to avoid future human and economic catastrophes. The almost incalculable GDP impact of the pandemic, and the value of prevention, are now visible to even the most conservative policymakers and governments. Hence interest and investment in these areas by the industry will likely increase.
To spur greater investment in infectious disease, policymakers will need to address both “push” and “pull” incentives. While funding grants (push) and regulatory incentives can help companies de-risk the early stages of development, they do not address the low return on investment. This low ROI is driven by the entrenched use of generics and by antibiotic stewardship by providers, who reserve novel antibiotics to mitigate resistance, resulting in infrequent prescribing and poor brand usage. Pull incentives would create more certain and attractive returns for successful antibiotic development.
These could include market-entry rewards, such as payments over multiple years to companies after approval or transferable vouchers that would extend the exclusivity period on other drugs in a company’s portfolio. These and other vehicles could draw more investment in new therapies. Meeting the expected rise in demand for new and effective treatments may require new networks and partnerships. For example, large pharmaceutical companies working closely with small biotechs, charitable foundations, universities and CROs to develop new products. And governments may need to make these drugs available to patients for free to ensure the general use that can impart herd immunity.
Such pragmatic approaches may be adopted as governments begin to see the societal costs and productivity impacts of other, less visible, but also widespread diseases such as Alzheimer’s.
The need for speed
Pharma is the most highly regulated industry in the world. But COVID-19 is raising questions about the impact on drug development of a conservative regulatory regime. The traditional priority of regulators was, “Do no harm.” The urgency of the present crisis is shifting that priority to “Test, treat, and prevent now.”
Clearly, regulators are exercising greater pragmatism and are showing interest in sponsors better leveraging RWE and post-marketing surveillance to demonstrate safety. The suddenly evident fragility of global healthcare systems, as well as the lack of reliable real-world data on infectivity and even hospitalization rates, has made the need for more credible and actionable real-world information obvious and urgent. This is a huge opportunity for sponsors and healthcare systems to deliver what regulators and policymakers desperately need.
Parexel is currently engaged in a considerable number of trials with RWE elements in the COVID-19 space. For COVID-19 we are seeing RWE now being used early to identify treatments for further study and to accelerate drug development. RWE also presents an opportunity to leverage synthetic control arms particularly impactful for accelerating development of new treatments for oncology and rare diseases.
Products for other conditions may follow this emerging model. Regulators recognize that data collected on drugs and treatments in traditionally randomized and controlled trial settings must be complemented by data from the real world. In other words, they appear to be moving from being risk-averse about RWE to prudently enthusiastic. This is an opportunity for the entire healthcare system to accelerate the speed of development without sacrificing safety, efficacy, or affordability – an unprecedented chance to innovate more quickly. A year from now, we will see if we have been able to leverage what we are learning for conditions other than COVID-19.
An opportunity in a time of crisis
The COVID-19 crisis is powerfully demonstrating the value of medicine and drug development –namely, how it keeps us safe and productive. People are becoming increasingly interested and invested in what the pharmaceutical industry does and how it does it, understanding that in both the long- and short-term, pharma is the industry that will ameliorate and end the economic dislocations and misery the virus has brought. Not only will the crisis change the way the public views the industry, but it will also change the way governments engage with it. As a society, we may come to accept that we need to provide incentives to ensure patient access to treatments unconstrained by cost. We cannot afford (and we never really could) to deny anyone timely access to treatment.
Going forward, we in the industry will need to ask ourselves if we have been truly creative in responding to COVID-19. What new technologies have we embraced? How have we changed the ways we do business, develop drugs, and treat patients – not only for COVID-19 but for every condition? If nothing else, the COVID-19 pandemic has shown us that the entire healthcare ecosystem – from drug discovery to development to regulation to market access and health care – must become more efficient and useful to patients. The future has arrived early, and our healthcare paradigm must shift. If the various players in the pharmaceutical industry can collaborate to deliver products rapidly beyond the current emergency, then we will be far better prepared to withstand the next global outbreak, and whatever comes after that.
Paul Bridges, Ph.D., Corporate Vice President, Worldwide Head of Regulatory & Access. Paul heads Parexel's Regulatory & Access organization worldwide and is currently based in Dublin Ireland. Prior to his current role, Paul headed the Americas Integrated Product Development (IPD). He earlier served as Vice President European Account Management for Parexel Consulting after a term as Senior Director of the consultancy’s regional UK IPD consulting team. Paul originally joined Parexel as a Principal Consultant providing strategic regulatory advice on all aspects of drug development with a special focus on Chemistry, Manufacturing and Controls (CMC).
Some of those differences are already becoming clear. Few scientists doubt that the novel coronavirus will be the last to emerge. There will be more generous incentives for companies to invest in developing vaccines and infectious disease (ID) drugs. The public and policymakers will push for the accelerated development of new and affordable medicines, as the pandemic has shined a bright light on disturbing healthcare inequities. Accelerated development will demand more real-world evidence (RWE) – with concomitant greater transparency in industry-regulatory communications and relations – as well as adaptive and hybrid trials to make activities in all stages of development more parallel and less sequential. At the same time, trials will become more decentralized and patient-centric to increase convenience for enrollees.
There is a theme emerging in all these changes: a new pragmatism. The sooner companies can adapt, accelerate change, and plan for tomorrow’s challenges, the stronger their positions will be. And the better prepared they will be to continue creating and marketing new drugs for patients who need them.
What the new pragmatism will mean
In our daily lives, whatever we can do remotely, we’re now doing. In many instances, we’re discovering it is more efficient. The same will be true in drug development. Whatever can be done remotely, will be, and that may prove to be for the better.
Clinical trials: The rise of new tools and approaches
Due to limited (or no) access to clinical sites, many trials have been put on hold. But for many others, including some of those run by Parexel, sponsors and managers are transitioning to distributed trials with remote monitoring and source document verification (SDV) to ensure that participating patients can continue to benefit.
While COVID-19 occupies the world’s attention, there are still substantial public health challenges in oncology, heart disease, and many other major and rare conditions. Clinical research must continue. For it to do so, sponsors and CROs must maximize their creativity while staying aligned with regulators. Drawing on our experience in late-phase studies, Parexel has have implemented technologies and approaches— such as eConsent, wearables, telehealth, telemedicine, and remote SDV – for remote monitoring of Phase II and III studies.
For example, telemedicine was not widely reimbursed by many insurers, including Medicare, before the pandemic. Now it is, and that will likely continue. The limitations that slowed the adoption of mobile technologies in clinical trials, including concerns about excluding bad or missing data, user errors, and the lack of device validation, will fade as the incentive to overcome them becomes compelling. The feeling that these tools would be “nice to have someday” has become “we need it today.”
We are unlikely to return to the old ways of conducting clinical trials once we have discovered the benefits of these new tools for researchers, patients, and regulators. And sponsors that become adept at using them will prosper in the future.
Regulatory: An increase in responsibility
The lives of regulators have changed dramatically, as most now have to work from home. Meetings that once took place in person – EMA scientific consultations, FDA end-of-Phase 2 meetings, even FDA Advisory Committee meetings – are now being held remotely if they’re being held at all. Sponsors must think pragmatically and learn to live with this new reality, even if it’s less desirable, and make the most of their available interactions with regulators.
In the last six weeks, 50 of the world’s regulatory agencies have issued new guidance on how sponsors should manage ongoing clinical trials and launch new ones. This guidance illustrates new flexibility regarding clinical trial management. However, standards on GCP compliance have not been lowered, and all amendments, protocol deviations, and adverse events must be reported diligently. Regulations are critical to safe drug development; loosening them can put patients in harm’s way.
Regulators are allowing sponsors greater independence in how they maintain compliance during this emergency. But sponsors should still maintain GMP and GCP compliance as tightly as possible to protect their development plans, ensure ultimate regulatory approval, and preserve the lifecycle of their products on the market. They have to balance creativity in conducting and managing compliant clinical trials with the expectation that they will have to satisfy regulators’ expectations. Importantly, ICMRA and its 29-member agencies have called for the conduct of large, well-designed, and controlled clinical trials to address COVID-19. To answer this call, sponsors must push the envelope of pragmatism by setting aside their differences and collaborating for the common good.
Once sponsors and CROs master this new regulatory environment – which has the potential to create new efficiencies, shorten response times, and reduce costs – there will be little incentive – scientific, operational, or financial – to return to old ways of operating. That genie is out of the bottle.
GMP enforcement: Remote rigor
Today, manufacturing plants around the world in receipt of regulatory enforcement letters are trying to retool and remediate their operations to get back into compliance quickly and cost-effectively, calling on experts for help. But those experts cannot now travel to sites in India, South Korea and China, and who knows when they will be able to? International auditing guidelines allow for remote auditing; regulatory authorities are issuing guidance to better facilitate them during the pandemic; and experts and starting to direct and monitor remediation efforts remotely, using video, virtual reality, and other advanced tools.
In the future, we can expect that experts will spend less time on planes, less time navigating new environments, and more time working on problems. This will be better for patients, manufacturers, supply chain managers and regulators, and more cost-effective for everyone, including payers.
Major regulators have largely discontinued manufacturing plant inspections for the time being, or do what they can do remotely. But they have not lowered their expectations that plants must be GMP-compliant. Indeed, it’s not unreasonable to expect more scrutiny as supply chain disruptions increase the risk of GMP deviations. This is no time for manufacturers to relax their GMP focus and discipline.
Where investments will move
For many years now, funding for R&D in infectious disease treatments or vaccines has come mainly from government entities, such as the U.S. National Institute of Allergy and Infectious Diseases, and philanthropic organizations, including the Bill & Melinda Gates Foundation. The biopharma industry has invested its development dollars in other areas, and infectious disease programs currently represent less than 2 percent of the overall development pipeline. The COVID-19 pandemic has revealed the enormous danger (and cost) of not having vaccines to hand, and society may be ready to spend more on reimbursing and rewarding good drugs and vaccines to avoid future human and economic catastrophes. The almost incalculable GDP impact of the pandemic, and the value of prevention, are now visible to even the most conservative policymakers and governments. Hence interest and investment in these areas by the industry will likely increase.
To spur greater investment in infectious disease, policymakers will need to address both “push” and “pull” incentives. While funding grants (push) and regulatory incentives can help companies de-risk the early stages of development, they do not address the low return on investment. This low ROI is driven by the entrenched use of generics and by antibiotic stewardship by providers, who reserve novel antibiotics to mitigate resistance, resulting in infrequent prescribing and poor brand usage. Pull incentives would create more certain and attractive returns for successful antibiotic development.
These could include market-entry rewards, such as payments over multiple years to companies after approval or transferable vouchers that would extend the exclusivity period on other drugs in a company’s portfolio. These and other vehicles could draw more investment in new therapies. Meeting the expected rise in demand for new and effective treatments may require new networks and partnerships. For example, large pharmaceutical companies working closely with small biotechs, charitable foundations, universities and CROs to develop new products. And governments may need to make these drugs available to patients for free to ensure the general use that can impart herd immunity.
Such pragmatic approaches may be adopted as governments begin to see the societal costs and productivity impacts of other, less visible, but also widespread diseases such as Alzheimer’s.
The need for speed
Pharma is the most highly regulated industry in the world. But COVID-19 is raising questions about the impact on drug development of a conservative regulatory regime. The traditional priority of regulators was, “Do no harm.” The urgency of the present crisis is shifting that priority to “Test, treat, and prevent now.”
Clearly, regulators are exercising greater pragmatism and are showing interest in sponsors better leveraging RWE and post-marketing surveillance to demonstrate safety. The suddenly evident fragility of global healthcare systems, as well as the lack of reliable real-world data on infectivity and even hospitalization rates, has made the need for more credible and actionable real-world information obvious and urgent. This is a huge opportunity for sponsors and healthcare systems to deliver what regulators and policymakers desperately need.
Parexel is currently engaged in a considerable number of trials with RWE elements in the COVID-19 space. For COVID-19 we are seeing RWE now being used early to identify treatments for further study and to accelerate drug development. RWE also presents an opportunity to leverage synthetic control arms particularly impactful for accelerating development of new treatments for oncology and rare diseases.
Products for other conditions may follow this emerging model. Regulators recognize that data collected on drugs and treatments in traditionally randomized and controlled trial settings must be complemented by data from the real world. In other words, they appear to be moving from being risk-averse about RWE to prudently enthusiastic. This is an opportunity for the entire healthcare system to accelerate the speed of development without sacrificing safety, efficacy, or affordability – an unprecedented chance to innovate more quickly. A year from now, we will see if we have been able to leverage what we are learning for conditions other than COVID-19.
An opportunity in a time of crisis
The COVID-19 crisis is powerfully demonstrating the value of medicine and drug development –namely, how it keeps us safe and productive. People are becoming increasingly interested and invested in what the pharmaceutical industry does and how it does it, understanding that in both the long- and short-term, pharma is the industry that will ameliorate and end the economic dislocations and misery the virus has brought. Not only will the crisis change the way the public views the industry, but it will also change the way governments engage with it. As a society, we may come to accept that we need to provide incentives to ensure patient access to treatments unconstrained by cost. We cannot afford (and we never really could) to deny anyone timely access to treatment.
Going forward, we in the industry will need to ask ourselves if we have been truly creative in responding to COVID-19. What new technologies have we embraced? How have we changed the ways we do business, develop drugs, and treat patients – not only for COVID-19 but for every condition? If nothing else, the COVID-19 pandemic has shown us that the entire healthcare ecosystem – from drug discovery to development to regulation to market access and health care – must become more efficient and useful to patients. The future has arrived early, and our healthcare paradigm must shift. If the various players in the pharmaceutical industry can collaborate to deliver products rapidly beyond the current emergency, then we will be far better prepared to withstand the next global outbreak, and whatever comes after that.
Sheela Hedge, Partner and Managing Director, Health Advances. Sheela is a leader in Health Advances’ biopharma practice, helping companies maximize the value of their assets and build winning market positions. Experienced in multiple therapeutic areas, she has particular expertise in metabolic and autoimmune diseases. Sheela brings a cross-sector lens to her biopharma clients, providing strategic advice on integrated solutions and convergent products. Sheela joined Health Advances in 2005 with a background in corporate strategy and health care provider operations.
