looks clearer to me now, after my first article (link), the Senate hearing (link) and more research. After the 2012 SONA where President Aquino mentioned initial successes in dengue prevention, there were newspaper articles which mentioned a rise in dengue (link), doubting its success. What I wonder is if the increased spread of dengue is related to climate change and to rapid urbanization in the Philippines – with the slums that result, the stagnant pools of water you often have there and of course a population density that makes it easier for the mosquito to travel from person to person.
Phase 3 Tests
The development of Dengvaxia goes way back, but the two most important Phase 3 tests started in June 2011 – one in Asia and one in Latin America (link). CYD 14 (Asia) had over 10 thousand volunteers while CYD 15 (Latin America) had almost 21 thousand volunteers. The active phase of CYD 14 ended in December 2013, that of CYD 15 in April 2014, with Sanofi reporting the success of Phase 3 some months later (link). Phase 3 is needed to apply for approval. The Philippines played a key role in all three test phases (link): 3,500 children were from the Philippines, setting up clinical trial sites in Alabang, Muntinlupa City (Phase 1); Barangay Del Remedios in San Pablo City (Phase 2); and Barangay Guadalupe in Cebu City along with Barangay Del Remedios (Phase 3) with Dr. Maria Rosario Capeding, head of the Department of Microbiology of the Research Institute for Tropical Medicine (RITM) – an agency of the Department of Health – playing a key role (link), including writing key scientific papers (link) and even experiencing how her own child got dengue (link). Seems the most important seroprevalence data came from San Pablo (link).
Since national data on seroprevalence (how many % of the population had virus exposure) did not exist, it was extrapolated to some areas where dengue is endemic (link). Some might consider this a doubtful methodology, but then again such authorities as Balik-Scientist Dr. Edcel Salvana have mentioned approximately 87% as the seroprevalence (see my previous article) and I see no reason to doubt that they are right, give or take a certain margin. He also writes (link) about why he sees the vaccine as good – if used properly. What is also important, however, is that the Phase 3 studies (link) included an active phase of follow-up for one year after the last dose of vaccine in the series (25 months from dose 1) and include a hospital-based follow-up period of four additional years. The follow-up phase for the Asian phase 3 study seems to have ended in November 2017.
A related research paper (with Dr. Capeding as a co-author) says that in the ongoing longer-term follow-up (from year 3 to year 6) to assess safety, we are monitoring the incidence of hospitalization for dengue as a surrogate end point for disease severity in order to evaluate a potential predisposition in vaccinated persons to increased severity of disease. I do wonder if there is a relation between the planned end of the follow-up phase and the warning by Sanofi not to vaccinate seronegatives (people without any virus exposure) anymore due to risk of severe dengue.
Getting Things Ready
In July 2014, then-Health Secretary Enrique Ona (link) sounded quite confident about the new vaccine (link) and the hope then was that it would be out by July 2015. The success of the Latin American study was announced by Sanofi on Sept. 3, 2014 (link). President Aquino met with Sanofi representatives on Nov. 9, 2014 (link) which was pretty soon after these events, then a year later in Paris on Dec. 1, 2015 when he was there for the Climate Change Conference – a meeting that was openly mentioned in the Philippine press (link), not done stealthily as some are insinuating.
There also was a dinner in Paris in May 2015 (link) involving ex-Secretary Garin and Sanofi, and before that Sanofi submitted papers for Philippine FDA requirements in January 2015 (link). Mexico, Brazil and the Philippines (link) approved the vaccine in December 2015. The end of December brought a number of events which were seen as rushed, which President Aquino in the hearing explained as being in order to get things done in his term, saying the new administrations often lose time in the beginning, and also explained why budget maneuvers were needed (link).
Now for Questions
Assuming the best (which I do now after having seen how Aquino acted at the hearing) there are still a number of questions. There were still some years of observation being conducted, who knew about this and who was (not) informed including possible risk factors, if already known then? As for monitoring, Dr. Melgar who was with the DOH when the program started has this to say (link): I know that the Family Health Office and the Epidemiology Bureau of the DOH have been doing due diligence in monitoring all adverse effects from the beginning. Sounds properly done.
Dr. Salvana would be the right person to ask on seroprevalence, and on why certain extrapolations were considered OK. I am satisfied with that for now, what I computed in my previous article still stands – those who WILL get sicker should be few. And I believe Aquino didn’t know the science.
What one knows
depends on eyes, ears and brain – and on their human and man-made extensions, meaning the people who inform and educate you. We all know about the information overload modern social media brings with the world practically spilling into our brains, including all sights and sounds. What more is a President constantly subjected to a barrage of information? So he needs his people. To filter what is important and what is not, to give him what he needs to be able to make decisions. What if they mislead him? He has to counter-check if possible. Mayors in cities have it much easier.
It is I think possible to get an intuitive feel for a city. Mayor Duterte may have known Davao in and out, therefore being instinctively able to tell bullshit from truth. At national level it isn’t that easy. Spurious drug lists have shown the limits of an intuitive, seat of the pants approach to governing. At national level and even more in specialized areas, one may need to have additional sources. Seems that the Presidential Management Office would have specialists (link), even if I am not sure if they are used as extensively and as focused as the staff of Germany’s Federal Chancellery (link) which has the job to (translated from German) obtain and keep ready the information the Chancellor needs for his/her work. Its divisions mirror related ministries and directly contact them for detailed information: Division 1 for interior and justice, Division 2 for foreign, defence and development affairs, Division 3 for social, health, labor, infrastructure and social matters, Division 4 for financial and economic matters, Division 5 for Europe and Division 6 for intelligence matters. With a nerve center like that, no need to rely only on Ministers – who are also politicians after all.
How one leads
Could it be that Aquino relied too much on his Cabinet members alone? A second opinion is good not only when one goes to doctors privately! It may be even more crucial in matters of state. The fact that ex-Secretary Garin now seems to have connections to the other side is a bit interesting. Somewhat like how PNPs Napenas was a candidate for an opposing party in the 2016 elections. Trust, but verify is usually better. And even a highly efficient apparatus can be sidelined at times, as was shown recently by the controversy in Germany regarding the herbicide glyphosate (link).
Another possibility is what I sense – that Aquino tends to push through with things he wants to do, at some point no longer reconsidering. That is a very Filipino trait which his successor also has, as in the Philippines, too much reconsidering can make one lose respect. The other side dislikes it, yes. But there is to me not much evidence of significant counter-indications known at that time, at least in a form understandable to laymen or managers. Specialists speak in details, managers think in terms of consequences, that gap must always be bridged whether in IT – my field – or elsewhere.
My personal opinion
There are terms like “lighthouse customer” for those who adopt a certain product first. Sometimes vendors (in any industry including mine) manage to make lighthouse customers pay normal prices. Other customers negotiate a deal which fairly considers their role in being one of the first to buy. Possibly the Philippines bought too many vaccines to soon at a slightly too high price. Asking for a refund is a maximum demand Sanofi will probably not accede to. But maybe a rebate as not all things were really made clear, since around 800 thousand kids will have to be monitored and a few, hopefully very few, may have to be hospitalized, is an idea. Sanofi does not want the PR damage from a long public conflict – nor does the Philippines want to look like a backwater where they accuse foreign firms of witchcraft. There are many ways forward. But let us look at 2016-2017 next.
Irineo B. R. Salazar
München, 15 December 2017
