DOH dengue trial protocol approved by PCHRD
Six years ago, Dr. Renato Dantes, one of the country’s top lung specialists and researchers, died due to dengue shock syndrome, which he likely got while on an out-of-town volunteer mission. He also got dengue a year before his death, but this did not deter him from continuing his pro bono work every time he felt his services were needed.
He was promptly diagnosed with dengue fever again and was still stable when admitted, but within 48 hours, his condition progressively deteriorated. His doctors, all experts in the field, felt helpless as they watched him bleed profusely, go into shock and breathe his last.
That was in 2008. Six years hence, we still don’t have any known effective cure for dengue. Thousands of Filipinos are still dying yearly due to the complications of dengue, supposedly a self-limiting viral infection transmitted by a mosquito bite, but in a significant proportion of cases, it can cause life-threatening complications like bleeding and dangerously low blood pressure (shock).
Clinical trial issue
Dr. Dantes came to mind when this issue on the ActRx TriAct clinical trial was brought up recently by acting Health Secretary Janette Garin.
My first impression was: Who cares about possible side effects in the future of a potential cure for a disease with no known cure, when you have a high-risk patient before you whose chance of dying is high? I have always considered myself an evidence-based physician, but in such cases, I would give the drug a try if the patient and his/her relatives would also consent after a detailed explanation of the pros and cons.
Acting Secretary Garin ordered the suspension of an ongoing clinical trial evaluating the effectiveness and safety of an herbal combination of artemether, artesunate and berberine, shown in an initial “pilot” study to offer remarkable benefits in dengue patients.
The second or confirmatory clinical trial or drug research was approved by Health Secretary-on-leave Enrique Ona sometime in September of this year, and was being conducted under the supervision of the Philippine Institute of Traditional and Alternative Health Care (PITAHC) through a multihospital, prospective study in six Department of Health (DOH)-retained hospitals.
‘Double blind’
A prospective study, especially when bias is eliminated by “blinding” the researchers or clinical investigators and providing a control group, is a reliable way to demonstrate the effectiveness and safety of a drug or product.
It’s called “double blind” when neither the investigators nor the enrolled patients know whether they’re receiving the active drug or not. All patients in both active-drug and placebo (dummy pill) groups receive the known beneficial supportive treatment for the disease, so no patient is left untreated and the participating patients are not being exposed to more risk than what he/she already has. The only difference is that one group gets the drug being studied, the other group does not; and the outcomes at the end of the study are compared in both groups. When the last patient has completed treatment, that’s the time when they open the “code” and the trial is “unblinded.”
Contrary to what has been said in some news reports, the protocol or research plan was actually evaluated thoroughly by the Philippine Council for Health Research and Development (PCHRD), which is recognized as the government’s expert arm in doing scientific health-related researches. From what I could gather from copies of communications between the DOH and the PCHRD on this research project, Dr. Ona requested the PCHRD sometime in April 2014 to review the results of a “pilot,” or initial study, which showed remarkable benefits of the product in dengue patients. The pilot study was done in 288 patients confirmed to have dengue at the San Lazaro Hospital.
New treatment modality
After doing a thorough technical review, Dr. Jaime Montoya, PCHRD executive director, confirmed the potential of the compound to be a new treatment modality for dengue, “which is a disease that remains to have no accepted or proven cure.” He noted that there were also no significant unfavorable or negative effects observed among the 288 patients included in the study.
Because of the apparently positive results of the initial clinical trial, an expanded and confirmatory follow-up trial, using a more stringent protocol (research plan) was called for. Dr. Ona again passed on this protocol to the PCHRD for review. The research experts at the PCHRD noted some areas in the proposed research protocolfor improvement, and for the results to be more conclusive, they proposed that the clinical trial should involve a bigger number of cases or patients. These recommendations were then relayed to Secretary Ona, PITAHC director general Dr. Jovencio Ordona and head of technical division Theresa Mendoza on April 22, 2014.
The research proponents followed the suggestions of the PCHRD, and developed an enhanced protocol, which Secretary Ona again requested the PCHRD to review sometime in July of this year.
Reviewing the final version of the research protocol, the PCHRD found it to be “complete in form and content based on the prescribed format.” It was also noted to be “scientifically valid and sound” to be carried out in hospitals. However, Dr. Montoya also stressed that “it is the responsibility of the research proponents to ensure that the appropriate ethical review and approval is obtained from the participating hospitals. The research proponent should comply with all pertinent and relevant procedural requirement, as required by concerned regulatory and monitoring agencies.” This evaluation and recommendation report was communicated to Secretary Ona in a letter by Dr. Montoya on Aug. 7, 2014.
No perfect research
There is no such thing as a perfect research. I have had the privilege to be invited to “peer-review” the research outputs of well-known and seasoned researchers before their papers are accepted for publication in some international journals or presentation in international conventions, and one can always find “methodological infirmities” or flaws in some of their researches. It’s so easy to be an expert evaluator in retrospect or hindsight, when the research project is already ongoing or has already been completed.
You can always find a loophole here or there. But you still appreciate these researchers for carrying out these clinical trials or research undertakings because their grit and determination fuel the engine of scientific advances and medical progress. If we would not allow researches until everything is perfect and no perceived adverse effect is seen, we will never be able to encourage any meaningful research in this country, and we will remain at the bottom of the list of nation-achievers in innovations, scientific research and development.
I appreciate the passion of acting Secretary Garin and I’m sure she means well. I have always admired her from a distance even since her first term in Congress, and I recall requesting Arvin Reyes, our senior editor then of Health & Lifestyle (H&L) magazine, to feature her on the cover, so she could be a role model to Filipino doctors and inspire them to be not only health champions but social advocates as well.
Critical decisions
But in the last six weeks that she’s at the helm of DOH while Secretary Ona is on extended leave, I think she has been doing things overenthusiastically, and some of her critical decisions could have benefited from a more dispassionate way of looking at both sides. It would also seem that some of her decisions, like her reorganization of the DOH and reversal of Secretary Ona’s decisions, were made with the perception or prior knowledge that Dr. Ona would already be asked to resign and she would be appointed as health secretary.
Among seasoned top executives in the private and government sectors, there are such traits as patience, humility, prudence and empathy for others. Aggressiveness, passion and overenthusiasm are tempered with these traits. Once Dr. Garin has fully learned these, I’m sure in the future, she would make a great health secretary and senator, or who knows, possibly president of the country. Meanwhile, just like Sen. Grace Poe, she has to be humble enough to accept that some lessons still have to be learned.
