Search This Blog

Tuesday, August 4, 2020

Why Producing a Vaccine As Fast As Possible May Not Be Good For Your Health

Now that 150,000 people have died from the Covid-19 pandemic within the US even the non-compliant are concerned at last. This article explores the dangers of “warp speed” production techniques when it comes to science and human subjects.  First, the pharmaceutical industry loves to get an accelerated pathway from the Food and Drug Administration (FDA), because it allows them to spend less money conducting expensive human subject studies and proceed to money making with an approved product. Accelerated approvals have become commonplace at the FDA, with minimal push-back, especially from the science-suppressing Trump Administration.
Here are the steps a drug developer ideally undertakes before a new drug is approved in the US
1.       Scientific research is conducted on a hypothesis to determine if the intervention produced  statistically significant results
2.       Results are subject to peer review, by a panel of experts, whom hopefully are not conflicted by pharma grants, compensation, or appointments
3.     Once a finding clears these steps, the next phase is to undergo testing with human subjects, which is initially conducted in a small study, probably populated with targeted or idealized patients, and this study is often observational and not a randomized control study, as a means  to save money.
4.     The next step, after a successful human-subjects phase is clinical testing, where the treatment or intervention is deployed with patients. Again, this phase may be observational and not the gold-standard of randomized controlled study which eliminates bias by double-blinding and other techniques.
5.     If the intervention is going to have a significant risk for a large population, the next step should be large scale population testing on a broad cross section of the society which is to receive the drug. It is this latter phase that the pharmaceutical industry is loathe to do, because it takes more time and money and, in many cases, mutes the benefits of the drug they are touting.
Malignant-How Bad Policy and Bad Evidence Harm People with Cancer, by Vinayak Prasad, MD, MPH, brilliantly explains the use of surrogate endpoints to accelerate drug approvals, which only reach level 3 in the drug development scale in some cases, before approval by the FDA. (Vinayak K.Prasad, 2020, pp. 23-50) To call this a rush to judgement of drug efficacy is an understatement. An accelerated approval is basically a provisional drug approval for a drug which hasn’t fully met the standards of the regular process. A surrogate endpoint is basically a substitution by pharma to shorten the approval process for a drug which has shown a statistically significant result, but which may have minimal value when applied to a real world patient population. In other words, if it only works on a few idealized patients without other comorbidities what is the value to society?
Most of the drug development in the US is paid for by the federal government through grants from Health and Human Services and citizens have a right to thoroughly researched drugs which are not merely approved by conflict-ridden FDA staffers who are ex-pharmaceutical employees. The current individual in charge of the “warp speed Covid-19 vaccination”, Moucef Slaoui, of GlaxoSmithKline is in fact so conflicted that he would be unable to obtain Congressional approval for the job, so instead the Trump Administration waived that requirement and allowed him to consult with the government without divesting of any of his pharma stock.
Of real concern with Operation Warp Speed is that important steps in the safety of an immunization will be minimized or eliminated because of the accelerated approval provision. This means that people who are less healthy may experience adverse side affects and could result in deaths. In other words, with the Covid-19 immunization Americans are the guinea pigs under accelerated approval.
In 2016, Dr. Prasad and Chul Kim reviewed all FDA cancer drug approvals and 66% were based on the jujitsu of surrogate endpoints. (Vinayak K.Prasad, 2020) They reviewed the use of surrogate endpoints through systematic review of available literature on scientific studies and found that 56% of the studies used to justify accelerated approvals did not even document the strength of the correlation they were using for surrogate endpoint justification. And 37% of the regular drug approvals did not document the strength of study correlation either. If statistical validation is not used then perhaps the findings are weak.
The FDA uses surrogate endpoints and other work arounds to justify “unmet needs” in healthcare, which is certainly the case for a Covid-19 vaccine. The goal in vaccine development is to eliminate susceptibility of disease, but corona viruses are notoriously difficult to development immunities. For example, the annual influenza vaccine is only partially effective in preventing influenza, and the vaccine has to be redeveloped annually because the virus evolves. This is essentially the situation the world is facing now with Covid-19. Of concern are the gladiator stakes the Trump Administration has created for several drug companies to compete to develop a vaccine. Being first for a vaccine would seem to be less important than providing the most effective vaccine for our population. And of course, a measure of efficaciousness is cost, which is born by US taxpayers and patients.
This is the healthpolicymaven signing off encouraging you not to sign blanket release forms when submitting to a medical procedure, do indicate that for which you agree and which you decline. It is after all your health, and that is no surrogate endpoint.
 Roberta E. Winter, MHA, MPA is a freelance journalist and health policy analyst who does not accept compensation from insurance, pharmaceutical, or medical device companies. This column, Straight Talk on Healthcare has been in continuous publication since November 2007.

References
Vinayak K.Prasad, M. M. (2020). Malignant-How Bad Policy and Bad Evidence Harm People with Cancer. Baltimore, Maryland, USA: John Hopkins University Press. 






3 comments:

David Altman said...

Almost every post finds me in complete agreement with the Healthpolicymaven. This post is an exception because several statements are not accurate. No FDA submission is being allowed which doesn't include large-scale population testing. Also, vaccine development has commonly not been profitable, which is of deep concern to many of us who have conducted clinical trials. We absolutely must accelerate the process when faced with a pandemic such as Covid-19. I agree we should be concerned about Moucef Slaoui having a conflict of interest, but he's also very qualified to potentially get the job done. The FDA has often conducted assessments with conflicts of interest before, so this is not unusual when the US definitely doesn't have the best drug approval system in the world. For a review of the 165+ vaccine candidate trials with human subjects, I recommend reading the NY Times review of each program published this past week. We should be praising the great scientific achievements to have brought development this far, which is exactly what Dr. Tony Fauci has done recently. I stand with Fauci, and Johns Hopkins University, as should all of us in this time of misinformation out of Washington.

healthpolicymaven said...
This comment has been removed by the author.
healthpolicymaven said...

The purpose of this article was to highlight the FDA process that informs accelerated review, which is widely used by big pharma to get provisional drug approvals, without completing follow-up testing.I cite Prasad's latest book with evidence gathered from his research and meta-analysis. I chose to use Operation Warp Speed to illustrate how the process works with the FDA. Of concern with the Trump Administration are science suppression and the political appointees who inhabit the FDA and other agencies. Yes, Dr. Fauci is doing a great job, but he has been silenced and minimized by Trump. If the current administration really cared about disease prevention it would have done something in January or February when the pandemic was already here. The latest initiative is a political ploy for Trump to gain re-election.