Good citizenship requires we all take a careful look at who we want to represent us. An election is fast approaching. Let’s do that…and quickly.
Among the astounding recent coverage of clearly planned active dismantling of our election by over-riding legal votes and appointing new state electoral members in swing states who will be installed to only vote for Trump, are attempts and actual successes in rewriting guidance of the CDC and FDA. Andy’s name appeared again in a recent short Star Democrat article and he was interviewed by The Spy Wednesday as pre-election coverage later also offered to his opponent. Flip- flop and spin abounded.
Andy Harris is taunting all of us in District 1 and even the entire US. He and two of his longtime friends now comprise a recently formed Data Safety Monitoring Board (DSMB) for an experimental COVID-19 drug trial. Not a vaccine, thank goodness, or at least not yet. But more on that later. It so happens that the drug CEO sponsor is also their friend. This is entirely irregular. An elected official has never placed him or herself in such a role. Not even once. Being a clinician has nothing to do with this and there are many, many boarded critical care/ICU physicians who could fill the committee role. So too, biostatisticians. Real ones. In true form of the new Republican Party, this is a simple bold abuse by Harris of his elected position. He is counting on you to view it otherwise. A little information can help you decide.
A DSMB is meant to operate in complete separation from both the sponsor of a new product, as well as the FDA from whom– if all goes well- they will seek a license for market approval and use. The DSMB is in the middle as they deliberate. Their evaluations are meant to be held in complete privacy from the sponsor and the regulating Agency. When there is an adverse event among the trial patients, it is the DSMB that reviews the data and evaluates risk of the proposed drug if widely deployed. They determine safety of the human trial participants as the trial accrues, as well as evaluate trial progress towards its stated IND protocol efficacy goals. However, under emergency use review (EUA) there is a bit of difference from a full license review: i.e. the members get to decide if observed benefits outweigh risks, and sometimes parse this for subsets of users if a large enough trial has been designed, not that there are not risks.
Each DSMB is intended to have one biostatistician and additional MD clinical members, typically each of them an expert in a clinical area relating to the product. In this case, in addition to no MD member being an infectious disease expert or pulmonologist, or intensive care expert (albeit there is crossover for some but not all anesthesiologist boards), there is also, and importantly, no biostatistician. No one on this very small DSMB has actual credentials which indicate they could calculate a required sample size for a rule they will support, determine an error margin or use sequential analysis to construct a mathematical boundary for stopping rules of safety or futility if their lives depended on it…. but yours and mine just might.
And don’t forget the lives of the people who will first be enrolled in these trials. More on that too because in addition to a very small, randomized trial with patient consent for the drug under review by this DSMB, there is a less obvious ongoing one for expanded use when circumstance will most likely delimit any truly informed consent under critically exigent conditions. Luckily having been used for years in the EU for erectile dysfunction, the drug probably won’t cause serious harm if patients are very closely monitored, nor perhaps ever get licensed for its new putative indication, but that is definitely not the point.
Back to facts. This Board lacks independence as well as the usual requisite skills. Andy should never have accepted or possibly even promoted his own membership on it. He brushes aside recent Politico criticism saying: “they don’t like Republicans.” A laughably easy excuse, but in this case, Politico surely has a point! He was dismissive of its contents, but there’s much more to know. You may want to pause here and read this short article before proceeding.
Andy Harris’ membership on any DSMB is a complete travesty as a show of gray ethics. It does not matter that he is “donating” his service (one wonders what that might actually consist of).No elected Congressman or Senator has ever tried to play such a role and never so boldly as to do so while also being a sitting member on a congressional subcommittee which has budget approval for aspects of the FDA! And just how did his CEO friend bring this 50 year essentially dormant product with only animal and in vitro evidence for this newer indication back to life as a listing in the FDA CoronaVirus Technology Accelerator Program? That’s a good question begging investigation of Harris’ subcommittee work for another day. But the drug also has expanded access, has changed its trial primary endpoint just recently after an early ‘look’ at the data (which has sample size and statistical ramifications that I hope the FDA reviewers will later evaluate), and could actually be utilized with no consent in certain situations. I hope this does not happen to you or me…because in one write-up the drug sponsor states it has already been previously used in “certain ICUs where it was felt to have benefit”. Previously used? Where? With consent? Whose? “Felt” to have benefit? Improperly tested hydroxychloroquine comes similarly immediately to mind, or convalescent plasma which had an encouraging sound, or zinc and all manner of other hopeful elixirs for COVID-19 disease.
But let’s examine the fact that Harris does not have the credentialed expertise needed to play the biostatistician that he claims as his dual role on the committee. How do I know? In addition to actually being one and having participated in domestic and international DSMBs which have always REQUIRED one fully credentialed biostatistician, designed, taught and analyzed 100s of clinical trials, actually have regulated biologic products via carefully vetted re-analyses of sponsor-provided trial data when employed by the FDA, Andy himself has told us so.
Years after his MD training, he enrolled in a shortened program designed for MDs to enhance their business skills of health and healthcare and remarks that he has been involved in papers that contained statistics. That’s it. He entered a program with coursework that was not in-depth statistics nor biostatistics and trial design, much less trial analysis. Of course it included business and investment models in medicine, and coursework centered on program goals of health policy and health finance and management. This was the MHS program – not to be confused with a substantially quantitative track of the longer MPH program, and certainly not that of a PhD, ScD or DrPH. Grants and articles mentioned, with appended authorships, are likewise no simple proof of his own quantitative expertise and applications. Nor just enrolling patients (“being involved in”) clinical trials along the way or appearing at an IRB (institutional review board). Andy is a part-time MD. Let’s leave it at that.
But serving with only two other members, one also without DSMB experience, and one a biologist, and having long personal relationships with not only both of them but also the CEO of the product now re-named RLF-100, which was first registered in the EU as aviptadil for ED, should give one pause. Not because it might not help less severely affected COVID-19 patients suffering due to putative ACE-2 downregulation (though some pulmonologists debate this mechanism), but rather because for some reason it never received license approval in the US for the first indication, either.
Rewriting and overriding guidance for EUA, Emergency Use Authorization, is also chilling. That is because these fast track submissions now fall first under EUA. Without adequate expertise on their own, one can imagine that these three members will simply flip through the pages offered by LavinConsulting, LLC- the registered outside, contract research organization (CRO) who has worked for this drug sponsor in the past, and go on their merry way pushing things forward if the CRO report so suggests.
The CEO drug sponsor himself even seems to agree, having been quoted as saying this DSMB “really doesn’t have much to do”. When the health and safety of human beings is at stake, there should at least be an appearance of much to do. Clearly someone else is handing the detailed and otherwise time-consuming analyses and assessments that are apparently just to be passed along as conclusions of the DSMB. Even so, the DSMB needs to have the expertise to carefully review the generated pages, find any errors, obfuscations and/or exaggerations made by the drug company, and carefully evaluate the provided data and analyses. It is, however, very interesting that the CEO seems to already know or expect little committee oversight, and feels confident enough to state it publically. I suppose that’s just a typical way to energize investors and venture capitalists, but I find it chilling if true. And Andy is meanwhile also our Congressman.
So why is Harris even doing this?
Does he really think the people in his district, ours, will believe it is only because he is trying to help the pandemic situation and not just his friend’s drug review and later marketing and investment efforts? How exactly did they get fast track review status? It’s time to learn more. For now, we know Harris has disabused mask wearing and closure or stay-at-home orders as nonsense or over-reach, calling it a “cult of masks”. He then walked that back in a mumbled statement about what he really meant–how masks might have caused complacency as singular efforts. It is not as if he earlier supported them. And he fought to open Maryland business and allow congregating more widely while case counts of those specific weeks increased in Dorchester County and then regionally. But in his interview with The Spy he also pushed the ideas again, incorrectly saying counts and the epidemic were abating and saying churches were singled out. As if church services, choirs, rally rants aren’t proven super-spreader events. Every talking point a spin version of his earlier days, except retaining his wishes to commemorate the Confederate States of America by leaving the Talbot Boys statuary on public courthouse property.
And then of course a list of his other congressional votes: repeal (without a shred of documented replacement value) the ACA and effectively eliminate pre-existing condition coverage, do not expand Medicaid that would have saved Maryland huge healthcare dollars, keep government in extended lockdown the last year, be an active member of the Freedom Caucus, support coal while defending removal of clean air and water regulations, demean the State Dept abroad, instead vote to waste available appropriations to build the ridiculous, never-to-be-finished Wall …. perhaps his version of immigration ‘reform’.
And he calls himself a physician? Do no harm?
So far we know we have a climate and healthcare opponent, a COVID-19 mitigation denier now entering a last push for back-walking spin, and a non-biostatistician meeting the needs of his friends per a hopeful money-making drug, all while being our elected Congressman. How and why and to what end he has inserted himself into the approval process for our regulated drugs and therapeutics and perhaps even FDA oversight and appropriations per his congressional committees, deserves investigation.
Talbot County wisely did not support him last go ’round and it is time to enlighten the rest of our District. Harris has even rudely and boldly claimed he does not have to worry much about winning or campaigning for this election given his opponent’s newer entry and her smaller campaign war chest. His purported help for watermen and agriculture has been too little, too late to make any real difference; it’s not just about a few belatedly acquired special work visas, his support of changes to trade agreements could have hurt. His constituents absolutely DO deserve his close attention and congressional assistance….all of them!
Now he plans to provide window dressing for Trump in Denton this weekend and get his name and a photo in some media just ahead of the next election. They’ll certainly make quite a performance duo. Harris is an embarrassment. Skip the rally lies and unhinged delusionary content delivered as rousing superficial chants to energize a real cult. Get to the polls or an official dropbox early; use the mail only if you must. We need a true representative, one whose primary concern is our interests and needs, not those of his political party, the current President, his friends, or himself.
Pamela Getson is a PhD biostatistician and former Director of the Statistical Core Group of Children’s Hospital while on Faculty at the George Washington University School of Medicine/Pediatrics. In addition to teaching and research, she designed and evaluated clinical trials, and later served as a senior math/biostat reviewer of data submitted in support of new biologic vaccines at the FDA/CBER. Now living on the shore permanently, she has resumed her love of sailing and nature.