Dr. Edsel Maurice T. Salvana
The Philippines is once again making headlines in the vaccine world in an unfortunate follow-up to the infamous Dengvaxia fiasco. The latest reason is the decision by our Food and Drug Administration to limit the use of the Sinovac COVID-19 vaccine (Coronavac) among frontline healthcare workers.
Coronavac is approved in many countries, including Turkey, Indonesia, Hong Kong, China, and Brazil, and there is no such limitation in any of these countries against use in healthcare workers. In fact, healthcare workers being among the most at risk is the entire rationale of an emergency use approval. The benefit of these first-generation vaccines is anchored in their ability to prevent severe disease and death in those at highest risk.
What is the basis of the limitation on Sinovac’s vaccine? A careful reading of publicly available material shows several efficacy rates reported by the countries where these clinical trials were held. Brazil’s Butantan research institute reported that the vaccine efficacy of Coronavac among frontline healthcare workers was 50.4 percent overall for at least very mild symptomatic disease. The vaccine efficacy for preventing disease that required medical attention was 78 percent, while the vaccine efficacy against symptomatic disease that required hospitalization was 100 percent. For a general population cohort in Turkey, the latest vaccine efficacy for Coronavac is 83.5 percent, and the vaccine prevented 100 percent of hospitalizations. Limited data from Indonesia showed a general population vaccine efficacy of 65 percent. None of these figures have been published in peer-reviewed journals, but data from the phase 3 clinical trials was made available to all regulatory agencies including the Philippine FDA.
Granting of an EUA has never been predicated on peer-reviewed publication of data. Pfizer, Moderna, and J&J’s EUAs in the United States all came out before their findings were published in a peer-reviewed journal.
Complete clinical trial data must be provided to the regulatory agency for proper vetting by its vaccine experts panel (VEP). In the case of the FDA VEP, the final Sinovac Philippine EUA acknowledged that the vaccine is safe and effective for use in adults 18 to 59 years old who are clinically healthy. It further stated that it may not be the best vaccine for frontline healthcare workers based on the Brazil trial. Shortly after the announcement of the EUA, it was confirmed that Coronavac was arriving on Feb. 28, 2021. In the meantime, there was no clarity as to when the delayed vaccines from the Covax facility which included Pfizer and Astra vaccines were going to arrive.
Due to the global shortage of vaccines and the delay of delivery of the Pfizer and Astra vaccine, the Philippine Government asked the interim National Immunization Technical Advisory Group (NITAG) for its recommendation on how to proceed since the arrival of 600,000 doses of Coronavac was imminent. The NITAG had previously recommended that COVID-19 vaccines be offered first to healthcare workers as the highest priority, followed by senior citizens, then those with comorbid conditions. The EUA stipulations effectively removed the first three priority groups, and the NITAG was faced with possibly recommending that the vaccine rollout start with the A4 group which consisted of non-medical front liners and essential workers. The final consensus was that healthcare workers should still be offered the first vaccine that arrived if this was at all possible.
The NITAG discussed this further with the FDA, and FDA director general Eric Domingo clarified two things. First, there was no prohibition against health care workers who did not directly care for COVID-19 patients. Second, even those who take direct care of COVID-19 patients could be vaccinated with Coronavac in the light of continued vaccine shortages as long as they are aware of the limitations of the data. The NITAG resolved to give all healthcare workers a choice between taking the Sinovac vaccine and waiting for the next available vaccine without losing their place in line.
This was done for three important reasons. First, it was very difficult to delineate frontline healthcare workers taking care of COVID-19 patients and those who see undifferentiated patients who may be COVID-19 infected and had not yet been diagnosed. Second, there was no clarity on when the next vaccine shipment was going to come and so any vaccine was better than no vaccine. Third, healthcare workers deserved to have that choice and the right of first refusal for any vaccine that arrived the soonest.
Unfortunately, the final NITAG resolution was preempted by an announcement that the vaccine rollout would begin at the Philippine General Hospital (PGH) on March 1 without the context that healthcare workers were being offered a choice. This occurred just as the resolution was being debated and finalized and caused confusion among PGH personnel. In addition, several physician’s groups started demanding that a health technology assessment (HTA) be performed on the Sinovac shipment before it was rolled out. The opinion of the legal team of the Department of Health was that a health technology assessment is unnecessary since the first Sinovac shipment was a donation, and therefore did not require a cost-effectiveness assessment.
When the NITAG resolution was finally released, the damage had been done. Many among the first healthcare institutions slated for Sinovac inoculation registered their reluctance to take the vaccine. PGH staff in particular staged a rally asserting that healthcare workers deserved only the best vaccine and many trainees were set to reject inoculation with Sinovac.
The Department of Health rolled out a series of townhalls the day before the Sinovac vaccines arrived. The next complication was that just before the townhalls commenced, there was an announcement that the arrival of the Astra vaccine was also imminent, potentially as early as March 1. March 1 was also slated to be the first day of the ceremonial vaccination rollout. This was communicated to the healthcare workers attending the townhalls, and it was made clear that they had a choice.
In yet another plot twist, following the arrival of the 600,000 doses of Coronavac on Sunday afternoon, it was announced that the Astra shipment was unexpectedly delayed due to global supply issues. Despite an official letter from UNICEF which was in charge of the vaccine shipments for the Covax facility, the announcement was met with skepticism and social media accusations of a bait and switch.
Undeterred, the ceremonial vaccination at the Philippine General Hospital and other COVID-19 hospitals pushed through on March 1, with a greater than expected number of healthcare workers electing to receive Sinovac despite the circumstances. Inoculations continued to pick up and on March 4, the delayed Astra vaccines finally arrived. In the meantime, a leaked unsigned HTA document purportedly showed that Sinovac had been found to be safe to use in low-risk populations, which was more or less consistent with the FDA recommendations. DOH has clarified that there are no final recommendations from the Health Technology Assessment Council, and that an HTA was necessary for procurement but not for continuing to roll out the donation.
Meanwhile, the debate rages on among doctor’s circles, social media, and in hospitals on which vaccine to take. To further complicate matters, the detection of the South African variant now casts some doubt on the Astra vaccine’s efficacy since there is an unpublished paper that states that vaccine efficacy against this variant could be as low as 10 percent. The World Health Organization continues to recommend the use of the Astra vaccine even in countries with detected South African variants as long as efforts are made to keep the proportion of variants low. There is also indirect evidence that Astra will continue to protect against severe disease for the South African variant.
In a recent Facebook post, I wrote that if I were a suspicious person, I would think there was some sort of anti-vaxxer conspiracy in the Philippines. There are just too many setbacks, plot twists, and seeming coincidences to believe these all happened without any orchestration. Being on so many committees and at ground zero for most of these occurrences, there does not seem to be any sinister manipulation to the best of my knowledge. What is undeniable though is that vaccines have once again been politicized, just like in the time of Dengvaxia. From a lifesaving resource that should be seen as a public good, vaccines are once again being used as proxy tools for influence, to score partisan points, and to sow doubt and intrigue. We have clearly not learned our lesson. Until we do, people will continue to needlessly die from vaccine preventable illnesses, which now include COVID-19.