3 February 2021: Ending Covid Updates
7 months ago, we started sharing the development of clinical studies on COVID-19 and we have been updating it regularly because we though it could be useful for having a more clear picture of the situation.
With the beginning of vaccinations we have started a new stage on this battle against coronavirus and we want to finish our updates with a final article about our experience with COVID as a CRO and how we expect the future to be.
We hope you find it interesting and please share with us your thoughts.
We wish you a happy and safe day.
Clinical investigation in the time of Coronavirus
As the pandemic continues to spread all over the world, the number of investigations and studies are also growing with the aim to better understand how the COVID-19 works and to find an effective medicine or vaccine in a record time.
Source: clinical trial.gov 1st December 2020.
Source: clinical trial.gov 1st December 2020.
Clinical studies on Coronavirus
Investigators all over the world are working together on clinical research in order to better understand the COVID-19.We have analysed one of the most popular database on clinical research: clinicaltrial.gov to get an in depth idea of the investigation efforts to fight the SARS-CoV-2.
We have found 4038studies related to COVID-19 (also SARS-CoV-2, 2019 novel coronavirus, and 2019-nCoV) on the 1st December2020. In a month the number of studies has increased by 231. The number of studies started picked in April and since then there have been less studies.
Source: clinicaltrial.gov 1st December2020
12.8% of all the coronavirus studies have been completed. Around 51% are recruiting and 22% haven’t started to recruit.
Source: clinicaltrial.gov 1st December 2020
Most of the studies are interventional (57%) which is a good news to get a new medicine or vaccine approved. And 43% are observational studies, also required to better understand the virus, the impact of each country’s measures, the evolution of the pandemic…
Source: clinicaltrial.gov 1st December2020
Most interventional studies are phase 2 and/or 3 (70% of the total). And 23% of the total are phase 3 studies and 7% are phase 4.
Source: clinicaltrial.gov 1st December 2020
Clinical trials submissions for Coronavirus (COVID-19)
Most countries have established a fast track to conduct clinical studies in order to start the investigation as soon as possible.
These are some of the measures taken by the main affected countries:
Under the instruction of the China National Medical Products Administration (NMPA), the Chinese Center for Drug Evaluation (CDE) has promulgated guidelines for filing new drug applications (NDA) for anti-COVID-19 drugs under a special review procedure, as well as technical guidelines on filing investigational new drug (IND) applications for anti-COVID-19 therapies and preventive vaccines. Under these guidelines, the time for obtaining an IND or NDA approvalis being significantly reduced.
For example, Gilead received IND approval from the NMPA for its Remdesivir in two days, significantly shorter than the default 60-day review period.
Zhejiang Hisun Pharmaceutical obtained a conditional NDA approval of its Favipiravir within 10 days, which allowed the company to launch the product before completing bioequivalence test and study on its efficacy in treating Covid-19 infections.
There are several types of “fast track” procedures available under the current Chinese regulatory framework.
The Italian Medicines Agency (AIFA) has implemented several specific measures:
Firstly, although the submission of requests for authorization of clinical trials and substantial amendments by e-mail is not acceptable, there is an exception for studies on COVID-19 (coronavirus disease 19) which can be transmitted to email@example.com (in cc to firstname.lastname@example.org) in case of impossibility to proceed via OsSC.
Secondly, it had taken some actions to encourage early access to therapies and facilitate the conduct of clinical trials on the efficacy and safety of the new therapies used for the treatment of COVID-19. In particular:
● Use of drugs in special circumstances: AIFA’s Technical Scientific Committee expressed a favourable opinion on the off-label use of some drugs for the treatment of SARS-CoV-2 infection and on the inclusion in the list of drugs that can be supplied pursuant to law 648/96.
● access to new drugs: AIFA has already officially approved the compassive use of five drugs and keeps an update registry on their website.
The US Food and Drug Administration (FDA) is promoting coordination with the European Medicines Agency for achieving convergence in regulatory aspects that can speed the trial processes for vaccine development. Check this article to find out more.
The FDA has outlined ways that existing regulatory options may make it possible to expedite access to therapeutics and vaccines with the potential to treat or prevent coronavirus disease 2019 (COVID-19). These include:
● Investigation of products approved for other indications for their potential use in treating COVID-19, including through collaboration with industry and interagency partners (e.g., NIH)
Leveraging existing data from trials being conducted in other countries
Utilizing the expanded access program to permit emergency use of certain therapeutics, and assessing data gathered through this process.
The Spanish Agency of Medicines and Medical Devices (AEMPS) is prioritising the assessment of clinical trials aimed at treating or preventing disease due to coronavirus. Sponsors or investigators who have a research project of this type must send a message to Clinical Trials Area (email@example.com) indicating in the subject line: “URGENT new CT COVID19”. A response will be given on the same day.
The German Federal Institute for Drugs and Medical Devices (BfArM) is giving special priority to COVID-19 clinical trials. This institution has set-up a dedicated e-mail address CT-COVID@bfarm.de for questions in connection with clinical trials related to COVID-19. Applications for scientific advice as well as clinical trials on diagnosis, prophylaxis or therapy of COVID-19 are processed free of charge during the COVID-19 pandemic.
Similarly to Spain, Italy or Germany, the French National Agency for Medicines and Health Products Safety (ANSM)is applying a fast procedure for clinical trials related to COVID-19 and for activating it sponsors should contact the following:
ANSM: firstname.lastname@example.org – (COVID-19 should be indicated)
DGS : email@example.com
Actually, thanks to these measures, the average evaluation timeframe has been reduced from 60 days to just 7 days.
South Korea is also strongly shortening the approval processes of key COVID-19 clinical trials.
The Ministry of Food and Drug SafetySouth Korea’s Ministry of Food and Drug Safety has recently confirmed that they will reduce evaluation of COVID-19 clinical trials to less than seven days.
For example, Gilead Sciences’ Remdesivir phase 3 clinical trial was approved in just 4 days.
UK Medicines and Healthcare products Regulatory Agency updated its special procedures for rapid scientific advice, reviews and approvals last August 26th, 2020.
The criteria for being considered eligible for a fast.track review is as follows:
Reviewed within 36 – 72 hours of submission:
- A study of a vaccine, treatment or diagnostic for COVID-19
- A study to understand immune response to COVID-19
- A study to understand prevalence or transmission of COVID-19
Reviewed within one-two weeks of submission:
- A study of the wider impact of COVID-19 (including on mental health)
- A study to enhance general understanding of COVID-19 (e.g. in specific patient populations)
- A retrospective analysis of existing data
Some studies considered of national interest or urgent public health are reviewed within 24 hours of submission.
How can the clinical investigation be shortened?
A new vaccine can take between 5 and 10 years to enter the market since the investigations start. With the new coronavirus, the experts are talking that it could take 1 year to have an effective vaccine to start treating the population.
Although the general process to approve a new medicine or vaccine hasn’t changed, there some factors that has shortened the timelines, such as:
The authorities compromise to reduce the time needed to obtain the approval in order to start the trial
Combine phases of the study: such as phase 1-2 or phase 2-3 studies
Once the trial has started: the recruitment process has been reduced significantly and the highly committed investigation team and patients makes the study run smoother.
Fast track to approve the medicine or vaccine studied.
How to manage clinical trials during Coronavirus (COVID-19)
Due to the Coronavirus Disease Pandemic and its impact in the global health system and broader society, International Institutions and National Competent Authorities have implemented a set of recommendations and extraordinary measures to deal with the arising challenges in this matter e.g.: trial participants being in self-isolation/quarantine, site closures, travel limitations, interruptions or delays that affect the supply of investigational products and health care professionals being committed to critical tasks.
Thus, the European Medicines Agency (EMA), European Commission (EC) and the Heads of Medicines Agency (HMA) have published a guide to assist sponsors on how to manage clinical trials during the COVID-19 pandemic in compliance with good clinical practice (GCP).
This set of recommendations has been created in accordance with the current guidance across Member States and in compliance with good clinical practice (GCP) and intends to provide guidance to Sponsors and should generally be agreed with investigators.
The feasibility of starting a new clinical trial (CT) or including new trial participants in an ongoing CT should be critically assessed by sponsors.
Conversion of physical visits into phone or video visits, postponement or complete cancellation of visits to ensure that only strictly necessary visits are performed at sites;
A temporary halt of the trial at some or all trial sites;
Suspension or slowing down of recruitment of new trial participants;
Extension of the duration of the trial;
Postponement of trials or activation of sites that have not yet been initiated;
Closing of sites. In case it is not feasible for a site to continue participation at all, the sponsor should consider if the trial site should be closed and how this can be done without compromising safety and well-being of patients already participating and data validity;
Transfer of trial participants to the current site to sites already participating in the trial or new ones may occur if unavoidable.
Critical laboratory tests, imaging or other diagnostic tests that have to be performed for patient safety may be done at a local laboratory (or relevant clinical facility for other tests) authorised/certified (as legally required nationally) to perform such tests routinely (e.g. blood cell count, liver function test, X-ray, ECG etc.), if this can be done within local restrictions on social distancing.
On-site monitoring visits may be cancelled; Implementing phone and video visits (without unnecessarily increased burden to the investigator site and taking into account trial participant integrity); Adapting the on-site monitoring plan when it is impossible to follow, supplementing it with (additional/increased) centralised monitoring and central review of data if possible and meaningful.
Protocol deviations may be higher than usual and a proportionate approach will be taken by the GCP inspectors when such deviations are reviewed during inspections, in particular where the best interest of the participant is maintained, and the participant is not put at risk.
Moreover, the document highlights that the safety of the participant is paramount, and risks of involvement in the trial, in particular with added challenges due to COVID-19, should be weighed against anticipated benefit for the participant and society (ref: principle 2.2 of ICH GCP). All decisions to adjust clinical trial conduct should be based on a risk assessment by the sponsor (ICH GCP section 5.0) and will be performed on each individual ongoing trial and the investigator of each individual participant.
There are also recommendations on reimbursement of exceptional expenses, communication with authorities, agreement with and communication to sites, changes to informed consent changes in distribution of IMP.
EU countries severely affected by the COVID-19 such as Italy, Spain or Germany have also published a guidance to this matter. The content of those documents is mostly covered by the EU-harmonised guidance aforementioned.
The Medicines and Healthcare products Regulatory Agency (MHRA), competent authority of the United Kingdom, has also published a Guidance which dictates a set of recommendations very similar to EMA’s one.
The American Food and Drug Administration (FDA) issues this guidance maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity during the COVID-19 pandemic. FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic
Research initiatives and Call for proposals
There has been some fast initiatives to help the study of the COVID-19, some of the main calls are the following:
COVAX has become the main global coordinated initiative. It is co-led by the Coalition for Epidemic Preparedness Innovations (CEPI), Gavi, the Vaccine Alliance, and the World Health Organization (WHO) – working in partnership with developed and developing country vaccine manufacturers.
The Coalition for Epidemic Preparedness Innovations (CEPI) is a key actor. To date, CEPI has provided initial funding to Curevac, Inc., Inovio Pharmaceuticals, Inc., Moderna, Inc., Novavax, Inc., The University of Hong Kong, The University of Oxford, The University of Queensland and a consortium led by Institut Pasteur. CEPI’s total financial pledges to develop vaccines against COVID-19 is now above US $1.4 billion in just three monthsThe coalition aims at pulling 2 billion USD globally.
The Bill & Melinda Gates Foundation, along with Wellcome and Mastercard are leading the COVID-19 Therapeutics Accelerator,which has awarded over $69 million in grants (August 10th, 2020).For more information: firstname.lastname@example.org
The World Health Organization has invited manufacturers of IVDs to detect SARS-CoV-2 to submit an Expression of Interest for assessment of candidate IVDs under the emergency use listing (EUL) procedure. It is intended to assist interested procurement agencies and Member States on the suitability for use of a specific IVD. The emergency use listing is weekly updated.
EU Commission’s main recent contribution is the announcement of €400 million in guarantees to support COVAX and its objectives in the context of the Coronavirus Global Response.
The National Research Council has openedtwo programsof funding based on call for proposals:
The Industrial Research Assistance Program (NRC IRAP)-Innovative Solutions Canada (ISC) COVID‑19 Challenge Program leverages existing government programs and activities to meet COVID‑19-related needs.
Applicant can be small and medium-sized businesses to refine and sell their product or solution to meet a COVID-19 related need
Pandemic Response Challenge Program, that is around 3 areas:
Rapid detection and diagnosis
Therapeutics and vaccine development and
Enabling adaptive responses
Applicants will be researchers at Canadian organizations.
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Other Useful information
International and National Institutions:
World Health Organization (WHO)- Coronavirus disease 2019 is gathering the latest scientific findings and knowledge on coronavirus disease (COVID-19) and compiling it in a database, updated daily.
European Medicines Agency (EMA): //www.ema.europa.eu/en
Elsevier: Novel Coronavirus Information Center
The Lancet. COVID-19 Resource Centre
BMJ Best Practice. COVID-19
The New England Journal of Medicine. Coronavirus (Covid-19)
Oxford Academic Journals. Free access to OUP resources on coronavirus and related topics
Cambridge University Cambridge University Press
Journal of the American Medical Association JAMA Network
Libraries or Publishers
Springer Nature. SARS-CoV-2 and COVID-19
Wiley Online Library. Covid-19: Novel Coronavirus Outbreak
Public Library of Sciences: PLOS: COVID-19 Updates