Instead of Developing a Vaccine on Our Own, the Philippines Should Participate in Global Collaborative Research
It's been more than a week since President Rodrigo Duterte's declaration to prioritize Covid-19 vaccine development, affirming our readiness to participate in clinical trials, and even offering a P10 million reward for its discovery.
But just how easy is it to discover and develop a Covid-19 vaccine? Simply put, it requires a higher level of technology, technical & manufacturing expertise and investment requirement that the Philippines, like most poor or developing market, doesn’t have. Estimates have calculated an investment of $135 to $500 Million for one vaccine to be out in the market
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Then how can our country gain faster access to potential vaccines for Covid-19? The Philippines should focus instead to attract international collaborative research on vaccine clinical development.
Once a candidate vaccine is discovered and ready for clinical investigation, it starts with clinical trials on a small number of volunteers to investigate its safety profile, how it is tolerated, and understand how the vaccine is handled inside the human body. Then, a few more clinical trials are done to check whether the vaccine works and the vaccine is safe. Typically it takes a few hundred patients to show proof of concept, and then another clinical trial with several thousand patients to establish its safety and efficacy that is acceptable to regulatory authorities such as the Philippine Food and rug Administration.
All these clinical trials are strictly monitored by the sponsor, a research ethics committee (REC) and by the regulatory authority. And this tiered approach to drug development typically takes years, hundreds of millions of dollars in cost, thousands of patient data, and all without guarantee for approval.
In a clinical trial, the sponsor is responsible for selecting locations where patients can participate and studies will be conducted. The Sponsor typically selects these locations based on a balance of factors such as availability of resources, disease prevalence, optimal medical care, ease of doing business, cost, regulatory & ethical considerations.
To shorten the development time, sponsors would select more locations to get more patient data. And this is the opportunity that our country should maximize, being a country with deep experience in numerous vaccine clinical trials--63 registered studies since 2012, according to the Philippine Health Research Registry.
But this alone doesn't guarantee our participation.
While the Philippines is active in conducting various clinical trials, its attractiveness to participate in Covid-19 clinical research remains low. Here are some reasons why, and what government agencies at the national and LGU level, and the private sector, should do:
1| Revise regulatory and ethical framework for Covid-19 research
Regulations have been promulgated by the Department of Health (i.e. DOH AO 2020-0010) and the Philippine Health Research Ethics Board (National Guidelines for Health and Health-Related Research 2017) for effective clinical trial conduct in the Philippines. However, these can become deficient in addressing sponsors needs during Covid-19 vaccine research.
Sponsors will look for a quick review turnaround while still enabling quality data generation and oversight. This need has already been recognized by at least 33 countries, which have quickly established specific laws, policies, regulations, guidance to address the needs for Covid-19 research. These countries are Australia, Austria, Belgium, Brazil, Bulgaria, Colombia, Cyprus, Denmark, Estonia, Finland, France, Germany, Hungary, Ireland, Italy, Kenya, Latvia, Norway, Peru, Poland, Portugal, Romania, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, The Netherlands, United Kingdom and USA.
We have an existing national framework called the Philippine National Health Research System (PNHRS) that can lead and coordinate this.
2| Warrant institutions to revise systems, processes and procedures for Covid-19 research
We have 46 Research Ethics Committees (RECs) accredited to Level 3 requirements that can perform ethical review and oversight for clinical trials that meets international standards. However, these RECs will need to redesign review systems, processes and revise or establish written procedures that would allow expedited review of clinical trials and ensure their availability to perform oversight during clinical trial conduct.
Typically, RECs in the Philippines reviews submitted proposals within one to three months from the time they receive the application. In Mainland China, ethics committee approval for Covid-19 research were reviewed within an average of 2.13 days from application. Opportunities to consolidate, expand or empower the Single Joint Review Ethics Board can also be explored.
Apart from the REC, public and private institutions where the clinical trial will be conducted should also establish or revise policies and guidelines to accelerate the setup, approvals and contracting before becoming attractive for Covid-19 research participation. It takes several months to negotiate and finalize institutional agreements in the current setup and this deters sponsors and even investigators from conducting trials at numerous sites in the Philippines.
3| Separate facilities for Covid-19 vaccine clinical trials
Vaccine clinical trials are routinely conducted in healthy participants, asking them to undergo multiple visits and procedures at research facilities. These visits, procedures and the needed patient care are performed by clinical research investigators and their personnel. They also collect, record, analyze and report the data, maintain accountability of the investigational vaccine and research specimens and perform various administrative activities. Lastly, the conduct and data the investigators generate are required to be monitored by sponsor staff to ensure scientific quality, subject protection and compliance to study conduct.
During an outbreak, however, study participants, research personnel and sponsor staff may be unnecessarily exposed and become infected during travel or their stay at the research institutions where infected patients also visit or are being managed. Sponsors, thus, would prefer to select research facilities that are separate from facilities that handle infected patients, allow continuous patient data flow and permit monitoring from sponsor staff.
It is suggested then to establish, conduct and that DOH and LGUs to allow vaccine trials at a community setting or outside a hospital environment as long as there is access to medical care, emergency medical facility, required equipment and facilities for specimen handling, processing and storage, vaccine storage and handling facility, study records facility, and REC oversight. We have a few investigators that have successfully established these in the past, but have done so after navigating a complicated and time consuming process.
4| Limit impediments to flow of research drug, equipment, supplies and human samples
Sponsors will prefer to conduct clinical trials in countries and institutions where shipment of drugs, equipment, supplies and human samples are unhampered. Drugs, equipment and supplies are typically imported by the sponsor while human samples (such as blood or tissue samples) are exported by research institutions to designated central testing facilities.
Unlike the Solidarity trial in Covid-19 patients where the endpoint to be reported is death, vaccine trials typically needs to analyze antibody levels against Covid-19 virus as the endpoint. The Philippines has various importation and exportation requirements set by the FDA, Bureau of Customs, Bureau of Quarantine and International Health Surveillance, National Telecommunications Commission (for equipment being used in research), and during this period, additional quarantine restrictions from the Inter-Agency Task Force on Emerging Infectious Diseases and even local governments.
These requirements heighten the logistical challenge from the sponsor and increase risk for non-compliance, poor quality or missing data. Thus, sponsors tend to avoid countries or institutions with challenging logistical requirements. The PNHRS can lead as well in coordinating measures to simplify requirement, reduce redundancy, and leverage digital tools to automate release of approvals, permits and licenses from the various government agencies.
5| Exempt patient participants, Sponsor and site/investigator research personnel from quarantine restrictions
Subjects participating in clinical trials, site research staff and sponsor personnel monitoring the study will require travel to the research facilities. These should similarly be unhampered or provided logistics to access the needed facilities and data to continue research. In some countries, home visits are even performed by research personnel to continue performing study procedures and collect data. There should be a mechanism to identify participants and personnel engaged in vaccine clinical trials and exempt them from quarantine restrictions while protecting against infection.
6| Provide incentives to investigators, licensed Sponsors/Contract Research Organizations and health care institutions for participating in vaccine research for Covid-19
This will encourage capacity building of our country's clinical research infrastructure.
I hope that these provide a starting point to mobilize actions to increase readiness and attractiveness for Philippines to gain early access to potential vaccines. As of April 22, 2020, there are already 52 registered vaccine clinical trials planned or being conducted in 15 countries and for 37 investigational vaccines (according to the Citeline Trialtrove database). While the Philippines has not yet been identified, selected nor disclosed to participate in these clinical trials, there is still a window to increase our attractiveness as most Covid-19 vaccine research are still in the discovery or early clinical development phase.
Conrado Vidad is a clinical research professional with 20 years experience in the academe, hospital, and pharmaceutical research industry and contract research organizations. He is a former president of the Philippine Clinical Research Professionals, Inc.
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