Tag Archives: career in clinical research

Hydroxychloroquine: An Effective COVID Treatment the Media Continues to Tag as “A Dangerous Drug”

On Friday, July 31, in a column ostensibly dealing with health care “misinformation,” Washington Post media critic Margaret Sullivan opened by lambasting “fringe doctors spouting dangerous falsehoods about hydroxychloroquine as a COVID-19 wonder cure.”

Actually, it was Sullivan who was spouting dangerous falsehoods about this drug, something the Washington Post and much of the rest of the media have been doing for months. On May 15, the Post offered a stark warning to any Americans who may have taken hope in a possible therapy for COVID-19. In the newspaper’s telling, there was nothing unambiguous about the science — or the politics — of hydroxychloroquine: “Drug promoted by Trump as coronavirus game-changer increasingly linked to deaths,” blared the headline. Written by three Post staff writers, the story asserted that the effectiveness of hydroxychloroquine in treating COVID-19 is scant and that the drug is inherently unsafe. This claim is nonsense.

Biased against the use of hydroxychloroquine for COVID-19 — and the Washington Post is hardly alone — the paper described an April 21, 2020, drug study on U.S. Veterans Affairs patients hospitalized with the illness. It found a high death rate in patients taking the drug hydroxychloroquine. But this was a flawed study with a small sample, the main flaw being that the drug was given to the sickest patients who were already dying because of their age and severe pre-existing conditions. This study was quickly debunked. It had been posted on a non-peer-reviewed medical archive that specifically warns that studies posted on its website should not be reported in the media as established information.

Yet, the Post and countless other news outlets did just the opposite, making repeated claims that hydroxychloroquine was ineffective and caused serious cardiac problems. Nowhere was there any mention of the fact that COVID-19 damages the heart during infection, sometimes causing irregular and sometimes fatal heart rhythms in patients not taking the drug.

To a media unrelentingly hostile to Donald Trump, this meant that the president could be portrayed as recklessly promoting the use of a “dangerous” drug. Ignoring the refutation of the VA study in its May 15 article, the Washington Post cited a Brazil study published on April 24 in which a COVID trial using chloroquine (a related but different drug from hydroxychloroquine) was stopped because 11 patients treated with it died. The reporters never mentioned another problem with that study: The Brazilian doctors were giving their patients lethal cumulative doses of the drug.

On and on it has gone since then, in a circle of self-reinforcing commentary. Following the news that Trump was taking the drug himself, opinion hosts on cable news channels launched continual attacks on both hydroxychloroquine and the president. “This will kill you!” Fox News Channel’s Neil Cavuto exclaimed. “The president of the United States just acknowledged that he is taking hydroxychloroquine, a drug that [was] meant really to treat malaria and lupus.”

Washington Post reporters Ariana Cha and Laurie McGinley were back again on May 22, with a new article shouting out the new supposed news: “Antimalarial drug touted by President Trump is linked to increased risk of death in coronavirus patients, study says.” The media uproar this time was based on a large study just published in the Lancet. There was just one problem. The Lancet paper was fraudulent and it was quickly retracted.

However, the damage from the biased media storm was done and it was long-lasting. Continuing patient enrollment needed for early-use clinical trials of hydroxychloroquine dried up within a week. Patients were afraid to take the drug, doctors became afraid to prescribe it, pharmacies refused to fill prescriptions, and in a rush of incompetent analysis and non-existent senior leadership, the FDA revoked its Emergency Use Authorization for the drug.

So what is the real story on hydroxychloroquine? Here, briefly, is what we know

When the COVID-19 pandemic began, a search was made for suitable antiviral therapies to use as treatment until a vaccine could be produced. One drug, hydroxychloroquine, was found to be the most effective and safe for use against the virus. Federal funds were used for clinical trials of it, but there was no guidance from Dr. Anthony Fauci or the NIH Treatment Guidelines Panel on what role the drug would play in the national pandemic response. Fauci seemed to be unaware that there actually was a national pandemic plan for respiratory viruses.

Following a careful regimen developed by doctors in France, some knowledgeable practicing U.S. physicians began prescribing hydroxychloroquine to patients still in the early phase of COVID infection. Its effects seemed dramatic. Patients still became sick, but for the most part they avoided hospitalization. In contrast — and in error — the NIH-funded studies somehow became focused on giving hydroxychloroquine to late-presenting hospitalized patients. This was in spite of the fact that unlike the drug’s early use in ambulatory patients, there was no real data to support the drug’s use in more severe hospitalized patients.

By April, it was clear that roughly seven days from the time of the first onset of symptoms, a COVID-19 infection could sometimes progress into a more radical late phase of severe disease with inflammation of the blood vessels in the body and immune system over-reactions. Many patients developed blood clots in their lungs and needed mechanical ventilation. Some needed kidney dialysis. In light of this pathological carnage, no antiviral drug could be expected to show much of an effect during this severe second stage of COVID.

On April 6, 2020, an international team of medical experts published an extensive study of hydroxychloroquine in more than 130,000 patients with connective tissue disorders. They reaffirmed that hydroxychloroquine was a safe drug with no serious side effects. The drug could safely be given to pregnant women and breast-feeding mothers. Consequently, countries such as China, Turkey, South Korea, India, Morocco, Algeria, and others began to use hydroxychloroquine widely and early in their national pandemic response. Doctors overseas were safely prescribing the drug based on clinical signs and symptoms because widespread testing was not available.

However, the NIH promoted a much different strategy for the United States. The “Fauci Strategy” was to keep early infected patients quarantined at home without treatment until they developed a shortness of breath and had to be admitted to a hospital. Then they would they be given hydroxychloroquine. The Food and Drug Administration cluelessly agreed to this doctrine and it stated in its hydroxychloroquine Emergency Use Authorization (EUA) that “hospitalized patients were likely to have a greater prospect of benefit (compared to ambulatory patients with mild illness).”

In reality just the opposite was true. This was a tragic mistake by Fauci and FDA Commissioner Dr. Stephen Hahn and it was a mistake that would cost the lives of thousands of Americans in the days to come.

At the same time, accumulating data showed remarkable results if hydroxychloroquine were given to patients early, during a seven-day window from the time of first symptom onset. If given during this window, most infections did not progress into the severe, lethal second stage of the disease. Patients still got sick, but they avoided hospitalization or the later transfer to an intensive care unit. In mid-April a high-level memo was sent to the FDA alerting them to the fact that the best use for hydroxychloroquine was for its early use in still ambulatory COVID patients. These patients were quarantined at home but were not short of breath and did not yet require supplemental oxygen and hospitalization.

Failing to understand that COVID-19 could be a two-stage disease process, the FDA ignored the memo and, as previously mentioned, it withdrew its EUA for hydroxychloroquine based on flawed studies and clinical trials that were applicable only to late-stage COVID patients.

By now, however, some countries had already implemented early, aggressive, outpatient community treatment with hydroxychloroquine and within weeks were able to minimize their COVID deaths and bring their national pandemic under some degree of control.

In countries such as Great Britain and the United States, where the “Fauci-Hahn Strategy” was followed, there was a much higher death rate and an ever-increasing number of cases. COVID patients in the U.S. would continue to be quarantined at home and left untreated until they developed shortness of breath. Then they would be admitted to the hospital and given hydroxychloroquine outside the narrow window for the drug’s maximum effectiveness.

In further contrast, countries that started out with the “Fauci-Hahn Doctrine” and then later shifted their policy towards aggressive outpatient hydroxychloroquine use, after a brief lag period also saw a stunning rapid reduction in COVID mortality and hospital admissions.

Finally, several nations that had started using an aggressive early-use outpatient policy for hydroxychloroquine, including France and Switzerland, stopped this practice when the WHO temporarily withdrew its support for the drug. Five days after the publication of the fake Lancet study and the resulting media onslaught, Swiss politicians banned hydroxychloroquine use in the country from May  27 until June 11, when it was quickly reinstated.

The consequences of suddenly stopping hydroxychloroquine can be seen by examining a graph of the Case Fatality Ratio Index (nrCFR) for Switzerland. This is derived by dividing the number of daily new COVID fatalities by the new cases resolved over a period with a seven-day moving average. Looking at the evolution curve of the CFR it can be seen that during the weeks preceding the ban on hydroxychloroquine, the nrCFR index fluctuated between 3% and 5%.

Following a lag of 13 days after stopping outpatient hydroxychloroquine use, the country’s COVID-19 deaths increased four-fold and the nrCFR index stayed elevated at the highest level it had been since early in the COVID pandemic, oscillating at over 10%-15%. Early outpatient hydroxychloroquine was restarted June 11 but the four-fold “wave of excess lethality” lasted until June 22, after which the nrCFR rapidly returned to its background value.

Here in our country, Fauci continued to ignore the ever accumulating and remarkable early-use data on hydroxychloroquine and he became focused on a new antiviral compound named remdesivir. This was an experimental drug that had to be given intravenously every day for five days. It was never suitable for major widespread outpatient or at-home use as part of a national pandemic plan. We now know now that remdesivir has no effect on overall COVID patient mortality and it costs thousands of dollars per patient.

Hydroxychloroquine, by contrast, costs 60 cents a tablet, it can be taken at home, it fits in with the national pandemic plan for respiratory viruses, and a course of therapy simply requires swallowing three tablets in the first 24 hours followed by one tablet every 12 hours for five days.

There are now 53 studies that show positive results of hydroxychloroquine in COVID infections. There are 14 global studies that show neutral or negative results — and 10 of them were of patients in very late stages of COVID-19, where no antiviral drug can be expected to have much effect. Of the remaining four studies, two come from the same University of Minnesota author. The other two are from the faulty Brazil paper, which should be retracted, and the fake Lancet paper, which was.

Millions of people are taking or have taken hydroxychloroquine in nations that have managed to get their national pandemic under some degree of control. Two recent, large, early-use clinical trials have been conducted by the Henry Ford Health System and at Mount Sinai showing a 51% and 47% lower mortality, respectively, in hospitalized patients given hydroxychloroquine. A recent study from Spain published on July 29, two days before Margaret Sullivan’s strafing of “fringe doctors,” shows a 66% reduction in COVID mortality in patients taking hydroxychloroquine. No serious side effects were reported in these studies and no epidemic of heartbeat abnormalities.

This is ground-shaking news. Why is it not being widely reported? Why is the American media trying to run the U.S. pandemic response with its own misinformation?

*

Note to readers: please click the share buttons above or below. Forward this article to your email lists. Crosspost on your blog site, internet forums. etc.

Steven Hatfill is a veteran virologist who helped establish the Rapid Hemorrhagic Fever Response Teams for the National Medical Disaster Unit in Kenya, Africa. He is an adjunct assistant professor in two departments at the George Washington University Medical Center where he teaches mass casualty medicine. He is principle author of the prophetic book “Three Seconds Until Midnight — Preparing for the Next Pandemic,” published by Amazon in 2019.

Fair Use Notice: Images/logos/graphics on this page contains some copyrighted material whose use has not been authorized by the copyright owners. We believe that this not-for-profit, educational, and/or criticism or commentary use on the Web constitutes a fair use of the copyrighted material (as provided for in section 107 of the US Copyright Law).

How the Pharmaceutical Industry became into existence?

The Birth of the Pharmaceutical Industry can be traced back to 1850 – 1875 where the first “authentic” drug was developed by extracting agents from plants.

In those years, there were also developed the microbial theory of disease, medicines and homoeopathy patent and there heavy use of powerful purgatives and cathartics medicines.

By 1875, the Drug Development becomes a science and the first synthetic drug was introduced. By 1900, vaccines and antitoxins form the basis of the new pharmaceutical industry.

From 1900 to 1925, began what is now known as the pharmaceutical century. The U.S. Pure Food and Drugs Act was passed (known today as the FDA) and the development of hormonal and chemotherapy was introduced.

After 1925, it began what is known today as the Antibiotic and Regulatory Era. Vitamins, antimalarials, anticarcinogenic compounds and anti-infectives discoveries were made. The FDA gains independence as a regulatory agency and is given compliance responsibility.

From 1950 thru 1975, a new generation of the drug became apparent. Vaccines for polio became mandatory, oral contraceptives appears on the market and cardiovascular therapies.

Also, an amendment to the Federal Food Drug and Cosmetic Act of 1938 Act was signed by President Kennedy to ensure that consumers will not be the victims of unsafe and ineffective medications. Additional information about this Act can be read here: Kefauver-Harris Amendments

The Globalization of the Pharmaceuticals industry started from 1975 thru 2000. New drugs therapies, new antiviral drugs, and the development of new drugs by biotechnology companies were in global high demand.

By 2000, over 2.8 million people participated in over 50,000 clinical trials and more research and development funding was increased.

R&D Expenditures by Body System

R&D Expenditures

Cost (Billions) Body System
7.0 Central Nervous System
6.0 Cancer, endocrine and metabolic
4.5 Cardiovascular
3.5 Infectious Disease
2.5 Biological and vaccines
5.3 Other

Current Trends in the Industry since the late 2000s

Biotechnology Medicines
Drug Intervention Targets
Vaccines

 

Role of Generic Drugs
Generic drugs account for over 47% of prescription drugs in the market in which 43 major prescription drugs come off patent by 2005.

What does this mean for pharmaceutical drugs?
Between 40% – 60% of sales are lost to the generic brand within the two years of coming off patent.

Factors that will impact the R&D future:

  • There has been over 40 mergers and acquisitions since 1985
    • Sanofi and Synthelabo
    • Zeneca and Astra
    • Monsanto and Pharmacia
    • Roche and Genentech
  • Employment grew at a 3% rate per year

Total Drug Development Time (Years)

Summary:
On average, it takes at least ten years for a new medicine to complete the journey from initial discovery to the marketplace, with clinical trials alone taking six to seven years on average. The average cost to research and develop each successful drug is estimated to be $2.6 billion.

Pharmaceutical Regulation

In 1902, about 10 children die after receiving a vaccine shot. The BIOLOGICS CONTROL ACT was passed to ensure purity and safety of serums, vaccines and similar products used to prevent or treat diseases in humans.

In 1906, “The Great American Fraud” reveals patent medicines laced with addictive drugs, toxic additive and alcohol.

In 1912, Public outcry over the sales of “snake venom” and other wonder cures.  The SHERLEY AMEND was passed to prohibit labelling medicines with false therapeutic claims intended to defraud the purchaser.

In 1927, the government forms a separate law enforcement agency called the Food, Drug and Insecticide Agency.

In 1937, about 107 people, including many children die after drinking a syrup called Elixir of Sulfanilamide. Due to safety concerns, The Federal, Food, Drug and Cosmetic Act (1938) was passed as the first attempt to regulate cosmetics and medical devices.

In 1962, the sleeping pill “Thalidomide“, developed what is known today as Grunenthal Pharmaceutical in Germany, resulted in thousands of birth defects in Western Europe. The KEFAUVER-HARRIS Drug Amend was passed to ensure drug efficacy and greater drug safety.

In 1983, the ORPHAN DRUG Act was passed enabling the FDA to promote research and marketing of drugs needed for treatment of rare diseases. This year there as an outbreak of HIV / AIDS cases.

In 1988, The FOOD and DRUG ADMINISTRATION ACT were established as the FDA under the Department of Health and Human Services.

In 1992, the pharmaceutical industry complained that life-saving drugs were being reviewed too slowly by the FDA. The PRESCRIPTION DRUG USER FEE ACT (PDUFA) is made into law.

Source:

Image: Courtesy of Google image

FDA website

Private information for college researched in the 2000s.

Let’s Talk Clinical Research Organization (CRO)

And the winner of the Worst “CRO” goes to?

Did you think I would tell? Besides, you would think it is my opinion and not a fact. I spent most of my career working directly with sponsors (pharmaceuticals, biotechnology companies and healthcare organizations) in their goal to submit drugs for FDA approvals.

So why would I think clinical research organizations aka CROs are that bad? They help sponsors with tasks, they themselves do not have the capacity or the resources or the time for.

Let’s examine some CROs (names replaced):

CRO Q: Back in the day, I used to hear ex-employees of this CRO talk about this CRO as “a  sweatshop (or sweat factory)”. It was a good place to gain experience and move on. This CRO is still in business and with a lot of sponsor’s project. I guess, things just stay the same as long as it does not hit the bottom line ‘$$$$$‘.

CRO T: This CRO has been around under multiple names. As soon as their employees hear the phrase ‘we lost a big project’ or ‘we are about to merge again’, employees move on or leave this company.

CRO C: This CRO model is to leased out their own staff (more like a recruitment agency) than a CRO. I used to know someone who was transferred from Europe to USA under this CRO. Eventually, my friend move on into a pharma client and it is happy ever since. Why would anyone want to work for this CRO and let them leased out your skills and services when you could just register as a business and do it yourself?

If you google around, you will see many questions about salary, interviews, and career options but there are no discussion of the various work environments you might encounter at a CRO.

CRO B: I briefly worked for this small CRO and let me tell you. It has got to be the worst experience yet. Not only managers are like total control-freaks aka ‘micro-management’ but their unhealthy work environment can make you sick (open-floor). There was no sense of team work. How can you work on this kind of environment? I prefer consulting, home-based projects for reasons like this one.

I have no time for bad-managers.

CRO P: The people at this CRO that have been there the longest are the ones that make it such a horrible place to work and there are only a few of them. High turnover CRO with a passive aggressive/sabotaging culture.

CRO I: What happened to the word ‘paperless’? Instead, manual review, re-work and more paper is available. In the world where technology has advanced, this CRO still using old technologies where paper-based process are implemented for EDC-based clinical trials.

CRO P: If you have a degree in chaos, a knack for scapegoating and the top notch ability to kiss the clients ass, this is the place for you. I am not saying this, by the way. I found it online and it sure made me laugh.

CROs All: These CROs who want you to account for every minute of your day. They produce nothing, they leased out your skills and experience to the sponsors. If the sponsor goes, you might be laid off.

Discussing our clinical research experiences at different CROs is the bread and butter of this industry. With so many outsourcing, mergers, who could you work for?

As one CRA posted online “deciding which CRO to call home in the current job booming environment is more difficult than before. The CROs (especially the mid-size and large ones) are filling up all the Internet job search websites with their multiple job postings. And if you talk to any of the recruiters, they will confirm that the company they represent is the best fit for you, they value their people, have an excellent health/dental/vacation day package, and have the hard to find “work/life balance” that eludes us all. Well, the sad truth is that there is no ideal CRO fitting that description. Oh, some have their merits (and some are better than others, for sure), but ideal they are not.”

I could not have agreed better with her point of view. With all the mergers and changes in the industry in the last few years, there is a new landscape to explore.

CROs have a bad reputation for ‘high turnover’. It is too bad that this issue of turnover is not addressed from the Top level. Management is probably too busy worrying about their multi-million dollars bonuses that what is going on at the office.

Good luck and hope this article brought you some insights to the clinical research world we live in.

For a better career solution, joining an employee-owned culture is best. There a few in the industry. I represent RA eClinica.

Our company was founded on the belief that those who contribute to the company’s success should own a stake in the company and benefit from its success. Because each of us has such a high degree of trust in one another we are all more motivated to please each other and to do excellent work. We are constantly striving for perfection, together.

If you want to take charge of your life, career and freedom, join us in this quest. Note that we are not a CRO nor an EDC vendor. We would like to think of us as ‘where Clinical Research meets Technology”.

Source: MedZilla

Source: LinkedIn Pulse