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Roche’s anti-inflammatory drug Actemra has failed in a phase 3 clinical trial that was testing to see if it improved the condition of patients with COVID-19 associated pneumonia.

The COVACTA trial of Actemra (tocilizumab) did not meet its primary endpoint of improved clinical status, or the secondary endpoint of reduced patient mortality.

The rationale behind the trial was that by inhibiting a chemical signal known as IL-6, Actemra would help to tackle the extreme immune reaction known as a cytokine storm in patients badly affected by COVID-19.

However the hypothesis looks somewhat shaky after Sanofi’s IL-6 Kevzara (sarilumab) also failed to produce results in a similar COVID-19 study.

Aside from being a setback in the effort against COVID-19, there are commercial implications too: sales of Actemra were better than expected during the first half of the year because of its use against the disease.

Actemra is already used to treat cytokine release syndrome (CRS) in patients who are undergoing CAR-T cancer therapy.

The Swiss pharma said it plans to continue with trials testing Actemra in other COVID-19 treatment settings, including in combination with an antiviral.

Although all four secondary endpoints were not met, there was a positive trend in time to hospital discharge in patients treated with the drug, which is also known as RoActemra in some regions.

The COVACTA study did not identify any new safety signals.

Roche said it will further analyse the full trial results, which will be submitted for publication in a peer-reviewed journal.

COVACTA was conducted in collaboration with the US government agency, the Biomedical Advanced Research and Development Authority (BARDA).

It tested safety and efficacy of intravenous Actemra added to standard-of-care treatment compared to treatment with placebo plus standard of care.

The primary endpoint of clinical status in hospitalised adult patients with severe COVID-19 associated pneumonia was measured by a scale that tracked patients’ clinical status based on the need for intensive care and/or ventilator use, as well as supplemental oxygen requirements.

Actemra is also being tested in the UK as a treatment for COVID-19, including in the RECOVERY trial, which includes several potential drugs and therapies.

Roche was in the unusual position of starting its trial after several smaller independent studies suggested Actemra could be used as a treatment for COVID-19.

Rav Seeruthun, Medical Director, Roche Products Limited said: “Whilst today’s news is incredibly disappointing, data from this trial will help scientists have a greater understanding of COVID-19.

“We should also celebrate the immense effort from so many groups to get to this point.

“There has been an unprecedented level of collaboration between industry, the NHS and others, in a way I’ve never seen before.  I hope it acts as a framework for future work beyond COVID-19.”

The government on Monday released guidelines of four schemes  for the development of bulk drug and medical device parks across the country to promote their domestic manufacturing.

These schemes of the Department of Pharmaceuticals were approved by the Union Cabinet in March this year.

‘In line with the vision of Prime Minister Narendra Modi, the schemes have been conceptualised for making India Atma Nirbhar in pharma sector,’ Union Minister of Chemicals and Fertilizers D V Sadananda Gowda said in a press conference.

The objective is to make India self reliant in production of 53 critical active pharmaceutical ingredients (APIs) or key starting materials (KSMs), and in production of medical devices, for which India is crucially dependent upon imports, he added.

The coronavirus crisis has exposed the weakness in global supply chains and posed threat to the health security of the country, Gowda said.

While proactive steps by the Department of Pharmaceuticals and the National Pharmaceutical Pricing Authority ensured steady supply of medicines, and prevented any shortage even during the lockdown, it was felt that domestic capabilities in production of APIs and medical devices have to be ramped up in order to eliminate any risks to the health security, he added.

‘The details of the schemes have been drawn up meticulously after having in depth consultations with stakeholders including industries and state governments. The selection of their location will be based on objective criteria, and in spirit of competitive federalism,’ Gowda said.

Similarly, eligible manufacturers will be selected for the PLI scheme on the basis of marks obtained in the evaluation criteria as per the guidelines, he added.

‘Supported by both central and state governments, these parks will be based on plug and play model with prior regulatory approvals, state of art infrastructure, excellent connectivity, affordable land, competitive utility charges, and strong R & D ecosystem and so on,’ Gowda said.

This will significantly reduce time and investment cost for setting up new manufacturing units. In addition, new units will be eligible for Production Linked Incentive (PLI) scheme of the government, he added.

‘I am sure that these schemes will elicit good response from interested companies. These parks will be able to attract significant investment as well as latest technology. Once operational, in about two to three years, these parks will generate thousands of direct and indirect jobs, reduce import dependency and, make India a global pharmaceutical hub,’ Gowda said.

The idea is also to cement India’s position as global drug supplier. As already known, in spite of various odds, India supplied critical medicines such as hydroxychloroquine and paracetamol to number of countries, he added.

‘Currently valued at around USD 40 billion, pharma sector can reach USD 100 billion by 2024 given the right support, and thus help achieve the PM’s goal of making India a USD 5 trillion economy by 2025. I am of a firm belief that these schemes will prove to be a turning point for the pharma industry,’ Gowda said.

According to Indian Drug Manufacturers’ Association (IDMA) Executive Director Ashok Kumar Madan, the industry has been waiting for these guidelines.

‘Given the right implementation, India can aspire to be self reliant in APIs/KSMs in 8-10 years time,’ Madan told PTI.

The industry’s wish is to also have the government support to utilise the idle capacities of the medium API units with a blanket permission from environmental approvals subject to their complying with the overall pollution loads, he added.

This will help production of listed APIs in shortest possible time and also prevent these units becoming non-performing assets, Madan said. ‘We also look forward to an early announcement of the Pharma Technology Upgradation Scheme to upgrade the medium units from Schedule M To WHO GMP,’ he added.

GlaxoSmithKline is closing in on EU approval for its first-in-class BCMA-targeting drug Blenrep, after getting a green light from the EMA’s human medicines committee.

Blenrep, based on the antibody-drug conjugate belantamab mafodotin, has been recommended for conditional approval by the CHMP in adult patients with the blood cancer multiple myeloma whose disease has progressed despite at least four earlier therapies.

Prior drugs have to include an immunomodulatory agent, a proteasome inhibitor and a CD-38 monoclonal antibody, says the CHMP.

The positive opinion put belantamab mafodotin on course for approval on both sides of the Atlantic, after an FDA advisory committee voted 12-0 in favour of the ADC at a meeting earlier this month, despite concerns about eye toxicity in some patients.

The CHMP opinion is based on two mid-stage trials – DREAMM-1 and DREAMM-2 – which showed that Blenrep achieved responses in around a third of patients who had received an average of seven prior treatments for the cancer.

Conditional approval means GSK will have to provide data from an additional phase 3 study comparing Blenrep with Pomalyst plus low-dose dexamethasone, the standard treatment option for relapsed and refractory multiple myeloma – in order to stay on the market.

“If approved, belantamab mafodotin will provide patients and physicians across much of Europe with a first-in-class anti-BCMA treatment option that works differently from other available therapies for this incurable disease,” said GSK’s head of oncology R&D Dr Axel Hoos.

For patients who have already been treated with the three major classes of drugs and no longer respond to them, the outlook is “still bleak,” according to the CHMP, with patients typically surviving three months or less.

Blenrep has been tipped as a future $1.5 billion blockbuster by analysts at Jefferies, although it is heading into what looks set to become a highly competitive category, with several other BCMA-targeting drugs following closely after in development.

In hot pursuit are CAR-T therapies from Bristol-Myers Squibb/bluebird bio and Johnson & Johnson, bispecific antibodies from Amgen, Regeneron and BMS/bluebird, and rival ADCs from AstraZeneca and BMS/Sutro Biopharma.

GSK’s drug has stayed ahead of the following pack thanks to its inclusion in the EMA’ PRIME scheme, designed to accelerate access to new drugs for diseases that desperately need new treatment options, as well as breakthrough and priority review designations in the US.

Blenrep is a key part of GSK’s ambition to regrow its oncology business, along with expanding the approval indications for PARP inhibitor Zejula (niraparib) – acquired as part of its $5.1 billion takeover of Tesaro – and getting its PD-1 inhibitor dostarlimab approved in its first indications.

Belgian biopharma company UCB is bringing up the rear of the IL-17 inhibitor category with its bimekizumab drug, so is celebrating new late-stage data showing superiority to the class leader.

The BE RADIANT trial pitted bimekizumab against Novartis’ Cosentyx (secukinumab) in the treatment of adults with moderate-to-severe psoriasis, and according to UCB is the first study to compare IL-17 drugs directly in this setting.

Bimekizumab performed better than Cosentyx across all the primary and secondary measures in the study, and according to analysts at Jefferies the trial “should facilitate UCB’s ability to carve a niche in the highly competitive psoriasis market.”

They think that could translate into peak sales of more than $2bn a year for UCB’s drug, up from their earlier estimate of $1.5 billion, assuming follow-up phase 3 trials in psoriatic arthritis and ankylosing spondylitis come good.

That would help ease the pain of the forthcoming patent expiries for the Belgian drugmaker’s current top-selling product Cimzia (certolizumab pegol), due in Europe in 2021 and in the US in 2024.

Cimzia accounted for €1.7 billion of the group’s 4.9 billion in sales last year, and bimekizumab has taken on even greater importance for the company after another pipeline drug – epilepsy candidate padsevonil – failed a clinical trial in March.

In BE RADIANT bimekizumab performed better than Cosentyx at achieving complete clearance of skin lesions – known as a PASI 100 response – at both 16 and 48 weeks. It also topped Novartis’ $3.6 billion blockbuster on the proportion of patients with a 75% improvement in skin lesions at four weeks.

That’s good news for UCB, but while it’s the first IL-17 drug that has shown superiority to Cosentyx in a head-to-head trial, other new biologics with blockbuster sales forecasts are also aiming to steal psoriasis market share from Novartis.

Just this week Eli Lilly reported that its IL-23 inhibitor mirikizumab outperformed Cosentyx in the OASIS trial, setting up regulatory filings later this year.

Meanwhile, AbbVie’s already-marketed IL-23 drug Skyrizi (risankizumab) also topped Novartis’s drug in testing and has got off to a swift start since its launch last year, with first-quarter 2020 sales of $300 million.

Jefferies notes that sales upside for bimekizumab are capped in a psoriasis market “dominated by competitors with large marketing budgets,” and suggests that UCB may now seek out a commercial partner to give it more marketing muscle.

The analysts are positive on UCB’s prospects overall, despite patent expires, with blockbuster sales also predicted for osteoporosis therapy Evenity (romosozumab) and zilucoplan for generalised myasthenia gravis.

AstraZeneca has begun a new agreement with Daiichi Sankyo to develop and market an antibody to treat cancer, worth up to $6 billion.

The deal covers DS-1062, Daiichi Sankyo’s proprietary antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2).

AZ and Daiichi are already collaborating on antibody-drug candidate, Enhertu (trastuzumab deruxtecan), which is already approved in advanced breast cancer.

The companies want to build on their success in the emerging TROP2 class, a protein that is overexpressed on the surface of 80% of tumour cells in triple negative breast cancer.

It is also found on the surface of most cells in non-small cell lung cancers and is associated with cancer cell growth and proliferation.

The deal focuses on DS-1062, which is currently in development for several TROP2-expressing tumours, with lung and breast cancers the most likely targets.

DS-1062 is a humanised anti-TROP2 monoclonal antibody attached to a cancer-killing chemotherapy called a topoisomerase I inhibitor.

The final component is the “linker” molecule designed to hold the chemotherapy in place while the drug travels around the body and only breaks once the antibody has become attached to the cancer cell.

AstraZeneca will pay Daiichi Sankyo an upfront payment of $1bn in staged payments: $350m is due upon completion, with $325m after 12 months and $325m after 24 months from the effective date of the agreement.

AZ will pay additional conditional amounts of up to $1bn for the successful achievement of regulatory approvals and up to $4bn for sales-related milestones.

The payments will be included in AZ’s results announcements as and when they are made.

The companies will jointly develop and market DS-1062 worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights.

AstraZeneca and Daiichi Sankyo will share equally development and marketing expenses as well as profits relating to DS-1062 worldwide, except for Japan where Daiichi Sankyo will be responsible for such costs and will pay AstraZeneca mid single-digit royalties.

Daiichi Sankyo will record sales in the US, certain countries in Europe and certain other countries where Daiichi Sankyo has affiliates.

Profits shared with AstraZeneca from those countries will be recorded as “collaboration revenue” by AstraZeneca.

AstraZeneca will record sales in other countries worldwide, for which profits shared with Daiichi Sankyo will be recorded within cost of sales. Daiichi Sankyo will manufacture and supply DS-1062.

Immunomedics already has a TROP2 class drug on the market – Trodelvy (Sacituzumab govitecan) was approved in triple negative breast cancer by the FDA this year.

The New Jersey biotech this month expanded a collaboration with Roche to develop Trodelvy in metastatic non-small cell lung cancer.

A US government agency is to give a further $472 million to biotech Moderna, after it announced plans to expand a phase 3 trial for its potential COVID-19 jab.

The latest funding from the Biomedical Advanced Research and Development Authority follows a tranche worth $483 million, awarded to kick-start development of Moderna’s mRNA-based vaccine codenamed mRNA-1273 in April.

Moderna has decided to expand the number of participants in a phase 3 trial after discussions with the FDA and with the Trump administration’s Operation Warp Speed.

The total number of patients involved in the phase 3 trial will be 30,000, and total funding awarded is around $955 million.

The phase 3 COVE study is expected to begin today and is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

After a review by the FDA, the trial will involve a 100 microgram dose and the endpoint will be prevention of symptomatic COVID-19 disease.

Key secondary endpoints include prevention of severe COVID-19 disease – defined as the need for hospitalisation – and prevention of infection by SARS-CoV-2.

Moderna says it is on track to deliver up to 500 million doses per year, and possibly up to a billion doses per year beginning in 2021 thanks to its manufacturing collaboration with Lonza.

The company also has a large-scale fill and finish contract with Catalent’s biologics facility in Indiana, following $1.3 billion in funding from investors in a public equity offering in May.

Moderna’s vaccine is based on cutting-edge but unproven technology, which uses a strand of mRNA to instruct the patient’s body to make copies of the “Spike” protein found on the surface of the SARS-CoV-2 coronavirus that causes COVID-19.

It’s hoped that this will prime the immune system to swing into action and neutralise the virus should patients become infected.

According to a regularly updated document from the World Health Organization, there are now 25 potential COVID-19 vaccines in clinical development.

A candidate developed by China’s Sinovac is at the top of the list, although Moderna’s drug may move up in the WHO’s reckoning following the latest development.

The device – named Shycocan- Scalene Hypercharge Corona Canon, is a small drum-like device, which can be fixed in offices, schools, malls, hotels, airports for disinfecting surfaces.

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A Bengaluru-based organisation received approvals from the US Food and Drug Administration and the European Union for a device that can contain the spread of novel coronavirus. Approval for manufacturing came in last week, officials said.

The device named Shycocan- Scalene Hypercharge Corona Canon, is a small drum-like device, which can be fixed in offices, schools, malls, hotels, airports or any closed area for disinfecting surfaces. The device has been proven 99.9 per cent effective in neutralising the Spike-Protein or S-protein that are present in this virus, thus completely cutting off its transmission from one person to another.

However, it does not cure an infected person but is highly efficient in containing the spread of deadly viruses in public areas, especially indoor spaces.

“We have given a ‘humanitarian’ licence to a few companies in India and abroad to manufacture this,” says chairman of the Bengaluru-based Organisation De Scalene Dr Rajah Vijay Kumar, whose brainchild it is.

Europe, Mexico and the US-based companies have also approached for licences and we would be giving permission to manufacturers allowing the production of the device in large numbers as the demand will spike in coming days, Kumar said in an interview with News18.

“We have done studies on how it performs — it neutralises the Spike protein or the S protein that is basic to the novel-coronavirus’ structure. So if you deploy this device everywhere, possibly there will be global containment of the virus,” Dr Kumar added.

The device was first shipped to the United States in March for its due testing. And lab tests have shown that that one device can cover about 10000 cubic metres area.

HOW DOES IT WORK?

The device floods a room or any indoor place with hundreds of electrons — even if an infected person comes into such a place, the electrons in the air would neutralise the potency of the virus in the aerosols caused by sneezing, cough, etc. It further neutralises the viruses that stick to surfaces. Thus drastically reducing the transmission via surface- or airborne transmission.

“We have got clearance from the US FDA agency under an enforcement directive for Covid-19 health emergencies. For the European Union too, we have got the Conformite’ Europeene, or the certificate of conformity for which the Shycocan was put through nearly 26 tests – such as safety, efficacy, whether it has any harmful effects, whether it interferes with the working of other devices, or whether other devices deployed in any place would interfere with the performance of this device. It has been cleared through all this,” Dr Kumar said.

Talking about the cost and manufacturing of the device, Dr Kumar added that the licence-holders would be fixing the cost and so far, in India, about nine companies have shown interest in manufacturing it, and three companies have already entered into a licensing agreement.

The COVID-19 pandemic has rapidly transformed much of the medical device, pharmaceutical, and vaccine industries. As Mary McDermott and Anne Newman note in JAMA, “Mitigation efforts [against COVID-19] interfere with all aspects of a successful clinical trial: efficient accrual and randomization, intervention adherence and delivery, and outcome collection.” Quarantine, isolation, and social distancing necessarily limit access to health care institutions for care. Shortages of medical resources and staff are also possible. As a result, many non-COVID-19 trials are being suspended or terminated. Large pharmaceutical manufacturers Eli Lilly, Merck, Pfizer, and Bristol-Myers Squibb have all announced delays in enrollment for ongoing studies and initiation of future studies. According to BioPharmaDive, as of May 15, 2020, nearly 100 companies and 240 trials have experienced disruptions. As such, the COVID-19 pandemic threatens to set back non-COVID-19 clinical trial research by several years.

On March 18, 2020, the Food and Drug Administration (FDA) published “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards.” Updated June 3, 2020, the document focuses on logistical considerations for clinical trial conduct in the setting of COVID-19, including impact on clinical sites, clinical investigators, and trial participants. Similar documents have been published by medical societies (for example, in oncology, radiology, cardiology, and neurology), and academic as well as industry statisticians, which attempt to convey practical advice for ensuring the “rights, safety and wellbeing” of participants while mitigating risks to trial integrity. Although such documents address critical concerns, the need to salvage whatever information can still be obtained from trials during this crisis is also of pressing importance. In particular, more clarity is needed with regard to statistical considerations in ongoing, suspended, or terminated clinical trials.

In addition, existing research efforts are largely being set aside in favor of a new, urgent goal: testing, treating, and preventing the disease caused by the novel SARS-CoV-2 coronavirus. This industrywide push toward solutions for COVID-19 resulted in a pivot away from existing lines of clinical research, which creates uncertainty as to how to proceed with future clinical trials. The FDA’s shift in focus toward COVID-19 vaccines and therapeutics—as evidenced by the transition of Center for Drug Evaluation and Research Director Janet Woodcock, MD, to COVID-19 vaccine development—compounds these concerns.

To address these issues, we discuss ideas on how to maximize the amount of data generated from existing trials, ensure participant safety, and increase the feasibility of clinical studies in times of crisis.

Participant-Centered Issues

Participants must be central to any decision to adjust ongoing clinical trials due to COVID-19. Below, we highlight some salient and generalizable considerations for individuals participating in clinical trials.

Any change that materially alters the nature of the trial must be addressed by protocol amendments. Given time constraints, amendments to multicenter clinical trials may be most expediently reviewed by a central committee rather than individual Institutional Review Boards. The COVID-19 pandemic has materially altered the risk-benefit assessment that allows for informed participation in clinical trials: an increased risk of SARS-CoV-2 exposure in health care settings without change in potential benefit. This dramatic change must be accounted for through re-consent of all trial participants. Decisions to unblind trials and offer early termination for participants in specific arms of a study or to individual participants who are especially vulnerable to COVID-19 may be warranted. This may be particularly relevant for participants in placebo or standard of care arms of clinical trials, given the relative lack of potential benefit. FDA officials have suggested in the past that use of external controls may have merit when the use of internal control arms is considered unethical. In any case, results should be returned to participants as they become available.

Other participant considerations during the conduct of the trial are also relevant. First of all, it is critical to limit in-person health status monitoring, such as blood tests and imaging, as much as possible. This is especially important for a participant in a high-risk group (such as an elderly oncology participant) or a participant who has to travel to receive care or be accompanied by others (such as children accompanied by a guardian, in which one must balance between care for the participant and risk of infecting others). Where monitoring must be done, participants should be evaluated outside the hospital or clinic setting where possible. Finally, in a slumping economy, attention must also be paid to whether enrollee compensation is ethical. Loss of health insurance or diminished income may coerce participants to remain enrolled in clinical trials, even as risks of leaving the home become more pronounced due to COVID-19. In all cases, the principle of “primum non nocere” (first, do no harm) must be the foremost concern.

Issues Related To Ongoing Trials: The Role Of Data Safety Monitoring Boards

Both the FDA Guidance and other similar documents recognize that many clinical trials may need to interrupt patient enrollment due to the impact of COVID-19. However, they offer little guidance on which statistical criteria could guide the decision to suspend trial activities, and whether and how to still analyze the data collected on experimental therapies.

In some cases, the Data Safety Monitoring Board could potentially perform an ad-hoc interim analysis based on formal stopping rules. For trials that collected most study outcomes, interim analyses could determine that the primary objective has been reached before the planned end of study. Futility stopping rules could instead help identify trials likely to fail even if continued. Both approaches could help minimize the number of patients that need to be enrolled in a trial during a crisis.

Nevertheless, more guidance is needed on when similar analyses could be appropriate. Two issues should be considered before performing interim analyses for early stopping, especially if unplanned. The first concern is the need to control the false-positive error rate (the probability that a trial would incorrectly produce positive results by chance) at a low, pre-specified level. This risk of false-positive findings is increased when assessing the same hypothesis multiple times, as would be the case in interim analysis. False-positive error rates could be controlled at pre-specified levels using multiple testing methods such as group sequential approaches. The second concern is ensuring the reproducibility of study results. To overcome this potential limitation, any unplanned analysis and decision rule for early stopping should be documented in amendments to the study protocol.

Optimizing Use Of Existing Data And Results: The Importance Of Dissemination

Many trials are likely to shut down during the current pandemic, but this should not translate into a loss of useful data. First, meta-analyses and methods to adjust for missing data, such as multiple imputation methods, can leverage data from discontinued trials to provide important information on the safety and effectiveness of tested therapies. Second, some protocol deviations due to COVID-19 may be unavoidable, which may increase the risk of bias in study results. Robustness of study findings could be evaluated in re-analyses of shared data based on different bias assumptions. Finally, the FDA should promote sharing of anonymous participant data and summary results from trials affected by the pandemic, even those terminated before their final analyses. More generally, it should enforce and expedite the reporting of study results. Even though the Food and Drug Administration Amendments Act requires timely reporting of results of applicable clinical trials to ClinicalTrials.gov, only 13 percent of trials post their results on this site within 12 months of trial completion.

Making the most out of data collected from trials during the current pandemic requires making such information widely available for re-analysis as quickly as possible without compromising participant safety and privacy. Notably, such calls for the widespread implementation of data sharing have been raised with regard to pediatric trials and rare diseases, which outside of a pandemic already face considerable challenges in enrolling limited numbers of participants in trials. In the context of a public health crisis, such populations are even more likely to be vulnerable to accrual problems, discontinuation, and nonpublication of study results.

Decentralization: A Future For Clinical Trials?

The current pandemic highlights a glaring inequity in the way that clinical trials have historically been conducted in the US: They are mostly performed in a few central locations, typically key urban centers. Given the disproportionate effects of COVID-19 on densely populated urban areas, it is expected that non-COVID-19 clinical trials conducted in such locations will struggle with enrollment and monitoring.

In contrast to traditional clinical trials, decentralized clinical trials are “trials executed through telemedicine and mobile/local healthcare providers,” as defined by the Clinical Trials Transformation Initiative. Prior to the pandemic, it had been widely reported that a lack of geographically diverse clinical trial sites negatively impacts study participation, especially for the enrollment of women, as well as participants from rural areas and racial groupstraditionally underrepresented in biomedicine. On the contrary, decentralized trials may help increase trial access and participant diversity.

The COVID-19 pandemic highlights an additional advantage for study decentralization: increased robustness of participant accrual in the face of a crisis. Indeed, decentralized trials could ensure continued accrual and monitoring of participants even when in-person care is no longer possible in some study locations. Still, the technical requirements for performing decentralized trials, such as remote monitoring, can make them infeasible for some therapy and disease settings with currently available technology.

Society should invest in the innovation required for widespread adoption of decentralized trials. Such innovation would promote distributive justice, ensuring that all populations affected by a disease have the opportunity to participate in—and reap the benefits of—clinical trials. Investment in technologies to help decentralize clinical trials would additionally increase the resilience of our country’s clinical research programs in the face of large-scale emergencies.

Viruses like SARS-CoV-2 can circle the globe with astonishing speed by taking advantage of human networks. The global medical research community couldn’t immediately contain it because it had no comparable network for defense — but we are moving quickly to create one. Employing adaptive clinical trials will help.

The initial response to Covid-19, driven by the best intentions, was to stand up more than 1,000 clinical studies. Many were small, uncontrolled, and unlikely to yield reliable information. This is one reason vaccines and definitive cures continue to elude us.

Even so, researchers have scored some remarkable wins. Less than a month after the first Covid-19 cases surfaced in late December, a research team sequenced the virus. Since then, other teams have identified cellular proteins that bind to it, shared data in open-access journals, and kicked off at least two dozen credible Phase 3 trials for vaccines, antivirals, and other treatments.

More milestones will follow as we expand research networks and exploit major innovations in clinical trial design. One advance in particular — an iterative, long-duration study known as an adaptive platform trial — is helping researchers up their game. The use of adaptive clinical trials allows them to simultaneously test multiple interventions against a single, shared control arm, add and eliminate treatments as the trial progresses, and update the study design as the treatment landscape changes.

In contrast, each traditional standalone Phase 3 trial must recruit patients to its own control group and test just one hypothesis. Even designing in techniques such as subset analysis and adaptation, these are extravagant undertakings that can’t match the supple efficiency and productivity of well-managed adaptive platform studies.

The adaptive clinical trials approach has already led to a series of high-value, actionable research results:

• In April, data from an adaptive platform study called the Adaptive Covid-19 Treatment Trial, or ACTT, from the National Institutes of Health, validated the clinical benefits of remdesivir, an antiviral agent, in patients hospitalized with Covid-19.
• A few weeks later, the similarly-designed Randomised Evaluation of Covid-19 Therapy (RECOVERY) trial in the United Kingdom demonstrated the benefits of dexamethasone, a widely used steroid.
• RECOVERY further showed that the malaria drug hydroxychloroquine provides little help for people with Covid-19, an invaluable contribution in the face of public confusion and pressure to use the medicine. It also showed that a combination of HIV treatments, lopinavir and ritonavir, was ineffective in treating the disease.

Other adaptive platform studies are launching as we write this. A coalition in which we participate, the Covid R&D Alliance, will soon share details about a large-scale adaptive program that drew inspiration from the U.K.’s RECOVERY project and from an initiative launched by the University of California, San Francisco, called I-SPY II.

The I-SPY II teams recently embarked on a Covid-19 trial involving several members of the Covid R&D Alliance. Another pandemic-centered program called REMAP CAP, which had been conceived before the pandemic emerged for just such an eventuality, has enrolled nearly 1,300 patients at 242 sites in 15 countries.

Imagine how the Covid-19 picture might look today if initiatives like these had been staged in advance — anticipating an inevitable pandemic — and networked into a globe-spanning adaptive platform ecosystem.

Such an uber-program would allow researchers on every continent to pool knowledge, data, analytics, materials, and other resources, and adding and deleting trial arms based on interim readouts, real-world data, and insights from the field.

Adaptive platform trials are not new. The methodology was already gaining traction in oncology and other areas before Covid-19 struck. They’re a subset of master protocol trials that Janet Woodcock, the Food and Drug Administration’s long-serving director for drug evaluation and research, and Lisa LaVange explored in a review article in the New England Journal of Medicine in 2017. This May, the FDA’s updated guidance on Covid-19 drug development recognized the potential of these trial designs, and the agency is likely to issue further recommendations.

Because the Covid R&D Alliance sprang from the crucible of this pandemic, its origin story is unlike any other: In the second week of March, with outbreaks raging on three continents, research heads at Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Novartis, and Takeda began exchanging information. We were soon joined by R&D heads of other major biopharma companies, as well as leaders across the biotechnology ecosystem.

Struck by the magnitude of the pandemic, our shared responsibility to act, and the scale of resources at our disposal, we communicated with minimal ground rules or administrative red tape. The alliance immediately began screening compounds for antiviral activity, building on work that members such as Novartis already had initiated.

Over the next two months, we put together a centralized screening mechanism for treatment candidates and started evaluating agents not only from our own pipelines but those submitted from the field.

We recognized that data-sharing protocols needed to change. The required summary-level study updates on ClinicalTrials.gov often lag a year behind data collection and analysis. And what researchers seek above all is patient-level data that currently isn’t available there.

Utilizing new analytic tools from the Bill and Melinda Gates Foundation as part of the International Covid-19 Data Research Alliance and Workbench, members of the Covid R&D Alliance and others will be able to look at summary-level statistics with a lag of just seven days. They will also be able to interrogate patient-level information from Covid-19 trials through a data-sharing platform created by TransCelerate, another industry consortium.

Covid-19 has also spurred collaboration around the tidal wave of real-world data from hospital records, insurance claims, and other sources. Real-world data makes it possible to design adaptive trials around a disease that is still new and poorly understood. Acting alone with proprietary analytics, no team could make sense of the data deluge. Through coalitions, though, we can divide up responsibilities coherently and share the analysis.

From the perspective of people afflicted with Covid-19 and their families, this essay paints too rosy a picture. Even as the global research community pushes toward new frontiers, we are saddened over the loss of life that might have been averted, and that continues today.

Viruses leverage animal and human networks. With an adaptive research ecosystem, we could begin to match them in speed, mobility, and evolutionary vigor, and ultimately keep the world safe.

The speed, flexibility and strong risk-benefit ratio of virtual clinical trials could all be highlighted in the assessment of potential Covid-19 treatments, according to industry bosses.

Dr Calvin H Knowlton, chairman and CEO of US healthtech firm TRHC (Tabula Rasa HealthCare), believes the use of new technologies such as AI in predicting medication safety could provide “a win for everyone” by keeping patients healthier and safer — even after the pandemic has subsided.

TRHC recently announced a partnership with Washington-based health plan provider Regence to virtually trial several different Covid-19 drug candidates, and assess the risk of adverse drug events (ADEs) in each.

Matt Hafermann, a clinical pharmacist in case management at Regence, said: “As Covid-19 has shown us, when novel viruses or diseases are discovered, having another method to pair with conventional clinical trials will help accelerate the scientific knowledge for treatment and prevention of diseases.

“Due to the global impact of Covid-19, collaboration between all sectors of healthcare is essential in identifying, assessing and developing therapies to minimise the virus’ impact.

“Through this partnership, we can help contribute to a long-term recovery plan that prioritises health and safety, while sharing results that aid other researchers working on strategies to combat Covid-19.”