A medical horror story
In a previous column, I appealed to the public to help me find a particular document so that the scientific community could come to a final judgment about the anti-dengue treatment touted by Health Secretary Enrique Ona as a medical breakthrough.
Based on my own investigation, it looked more like an unethical medical experiment perpetrated on our people rather than a real cure. Based on the paper trail of the development and use of the drug ActRx Triact, there was one study made by a Dr. Miranda et al., which might prove the safety efficacy of the anti-dengue drug. That study was missing despite the efforts of myself and other well-connected and highly competent researchers. While the evidence was already overwhelming that something was wrong, the Miranda study could have exonerated Dr. Ona and those who participated.
That study was leaked to me because of my appeal. And we can now make a final judgment.
The header of the document contains date and title, “FINAL REPORT MAY 19, 2014. The Impact of the Use of Artemether + Artesunate in Combination with Berberine (ActRx TriAct®) in Addition to the Standards of Care in the Management of Dengue: A Randomized Open-Labelled Clinical Trial.” The principle investigator is Dr. Elena A. Miranda. Named as sub-investigators are: Dr. Erwin V. Palsis, Dr. Maria Riza G. Maravillas and Dr. Talitha Lea V. Lacuesta.
Readers may be curious at this point as to who these people are. What are their qualifications? Are they employees of the Department of Health and therefore accountable to the general public for the work they do? If these considerations are important to the curious lay person, they are critical to the scientific community.
These are so critical in the assessment of the scientific claims of a clinical trial that it is recommended by the US FDA that affiliations and credentials be included in the report. No such information about these doctors is available from the document. But I did find out things about them from other DOH documents in my possession, something I will return to later.
What we do have in the report, in compliance with the technical guidelines for reporting, is the identification of the sponsoring company, ActRx Foundation. There is also the mention of another collaborator: Preferred and Proven Therapies, Inc. I do not know why PPPTI is even listed because the structure of the research team (roles, administration, oversight and monitoring functions, roles of the sponsor and collaborator) is not discussed, again contrary to the recommended guidelines.
Instead of such a discussion there is this somewhat embarrassing statement about the sponsor and collaborator on page 4 of the study: “The ActRx Foundation, Inc., is a non-profit foundation dedicated and passionate in discovering medical breakthroughs that can help save lives through the use of effective and safe medicines. The Foundation is devoted to contributing its resources in the elimination and treatment of dengue. In collaboration with Preferred & Proven Therapies, Inc., they have funded a pathway for a clinical trial using a patent pending ActRx TriAct® treatment...”
I call this an embarrassing statement because it sounds like company propaganda. The point of listing drug company sponsorship is so that those who will evaluate the study can understand possible conflicts of interest. Purists would prefer that drug companies do not sponsor clinical trials because there is clearly pressure, given the resources already spent on development and the possible profits to be gained, to find the drug safe and efficacious. But science must give in to practical considerations and drug companies do sponsor clinical trials because they are invested in drug development.
But competent investigators are at pains to ensure that a firewall exists between themselves and the company sponsor. Thus, research reports must make transparent the administrative structure and monitoring processes within the research. Both ethical drug companies and ethical investigators should prefer this. The outright “praise release” of the sponsors is unseemly in a scientific report.
Unseemly public private partnership
I will add, however, that the unthinking endorsement of ActRx and Preferred and Proven Therapies seems to mark this DOH engagement. Dr. Elena Miranda of San Lazaro Hospital, former director general Dr. Juvencio Ordonia of DOH-Philippine Institute for Alternative Health Care (PITAHC), and Dr. Efren M. Dimaano of San Lazaro Hospital are seen on the websites of ActRx Operations Group and Facebook Page of PPTI.
I encourage the reader to explore these sites because it is notable that most of the content on ActRx TriAct is based on the DOH memorandum order signed by Secetary Ona and the Miranda study. Personalities such as Angelina Jolie, Matt Damon and Oprah Winfrey are tagged by PPTI in repeated photos of the DOH order. Furthermore, in a seeming attempt to get funding, also tagged are big donor institutions like for example, the Rockefeller Foundation and a mortgage bank.
Looking at these sites made me glad my father has passed on. We have come a long way from the time when he, a professor emeritus of the UP College of Medicine and his colleagues, taught us that medical doctors were never to endorse drugs in any way, except that in prescribing the best choice, this might serve as an endorsement.
No FDA approval
Our hopes of finally finding that there was ethical review and approval by the Philippine FDA and the Philippine Council for Health Research and Development (PCHRD) are dashed by the copy of the report I possess. Contrary again to existing guidelines, no attachment shows these approvals.
Hexilon Alvarez President and Chief Executive officer of PPTI claims that they “had secured the approvals from the US FDA, which is under the US Department of Health and Human Services (USDHHS).” In truth what they have is a provisional approval by the “Bahamas Clinical Services at IAT Research Clinic” an Institutional Review Board (IRB) that is registered with the Office of Human Research Protection of the USDHHS.
An IRB must be designated by those who wish to deal with the USDHHS for research. A recognized IRB does not necessarily have the capacity to review the scientific integrity of a research proposal. The registration of the particular IRB that Alvarez cites is also listed in the OHRP as “deactivated.” Suffice it to say that Alvarez is engaging in misdirection at the very least when he states that there is US FDA approval.
Dubious business enterprise
However, the reference to a Bahamas IRB brings up another aspect of ActRx.
ActRx is a Bahamas registered corporation, something that should raise red flags. On the same website page that states its Bahamas registration, ActRx also says, “The statements and products referred to throughout this site have not been evaluated by the US FDA...Company is providing this site and its contents on an 'as is' basis and makes no representations or warranties of any kind with respect to this site or its contents. Except as specifically stated on this site, neither Company nor any of its directors, employees or other representatives will be liable for damages arising out of or in connection with the use of this site. This is a comprehensive limitation of liability that applies to all damages of any kind, including (without limitation) compensatory, direct, indirect or consequential damages, loss of data, income or profit, loss of or damage to property and claims of third parties..” Such wording would not be on the website of any reputable drug company.
A little more digging reveals even further how dubious ActRx and PPTI are. Robert Lewis Steele, together with Anthony Fedele Musso are patent holders of “ACT therapy” or “Tri-ACT” for dengue fever and malaria. News reports in Dec 2010 report the arrest of 3 persons by the NBI based on a complaint by Manny Pacquiao that that they used his name and image on websites and falsely claimed that he is a founding partner of a foundation to help people with dengue and malaria. One of those arrested was Anthony Musso. One of the Foundations using Pacquaio's name illegally is “buyactrx.org.” A google search reveals Anthony Musso is selling Triact through this company as well. One can find the same picture used by the bogus Pacquiao endorsed website in that website for Preferred and Proven Therapies, Inc.
Musso was also found guilty of violating the anti-fraud and registration provisions of the federal securities laws of the US in connection with his company, Nutrition Superstores. The judgment bans him permanently from acting as an officer or director of any issuer registered with the US Securities and Exchange Commission.
As to the science of the study itself, it is so bad that not a lot of expertise is needed to see its flaws. I suspect that the real experts will add to my necessarily short critique. Should the reader wish to make a deeper analysis, there is a standard for the conduct of drug trials for dengue to be found here.
But there are some basic flaws that anyone with general knowledge of research methods and statistics would notice. In my opinion, they are fatal flaws. The study is not a double-blind study and its randomization of the participants is questionable.
More egregiously, the only reference it makes to previous studies on safety and efficacy are those of “Dr. David Mundschenk and Dr. Kevin Bethel of the ActRx Foundation group of medical scientists.” The studies allegedly made by these two to prove that the Miranda trials are not standing on thin air, are not cited in the list of references.
In my first article on this drug I asked whether this was really a horror story wherein an unethical drug company and its local partners met with a DOH secretary ready to play fast and loose with the nation's health. I was wrong only in that I called ActRx a drug company. That gives it too much legitimacy. As for the rest of it, it is indeed a horror story. A very tawdry horror story. - Rappler.com