Tag: drug development

01/26/21

Learning from COVID Drug Development

© Ilkin Quliyev | 123rf.com

On December 11, 2020 the FDA issued an emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 Vaccine. Then on December 18th, the FDA issued an EUA for the Moderna COVID-19 Vaccine. The FDA News Releases for both drugs said the data provided clear evidence both vaccines may be effective in preventing COVID-19. The known and potential benefits for both drugs were said to outweigh the known and potential risks. “In making this determination, the FDA can assure the public and medical community that it has conducted a thorough evaluation of the available safety, effectiveness and manufacturing quality information.”

In December of 2019, no one knew COVID-19 existed and now there are two vaccines being distributed in the US that are both around 95% effective in preventing the novel coronavirus. Despite the unprecedented speed of their development, there were not any compromises with the safety or the scientific integrity of the process. According to Dr. Anthony Fauci, the speed was “a reflection of the extraordinary scientific advances in these types of vaccines which allowed us to do things in months that actually took years before.” He wanted to settle the concerns some people have about the rush of development and approval. Despite the politicization of the process, there was an independent body of people with no allegiance to the administration or to the pharmaceutical companies who were the first ones to review and then approve the data from the companies’ late-stage clinical trials. “We need to put to rest any concept that this was rushed in an inappropriate way . . . Help is on the way.”

The FDA requires that a vaccine be at least 50% effective, according to the latest guidance. By comparison, two doses of the measles vaccine is about 97% effective, and flu vaccines range from about 40% to 60% effective, according to the Centers for Disease Control and Prevention (CDC).

The FDA just finalized the guidance for EUAs in January of 2017. The purpose of this guidance was to explain the FDA’s current thinking on the authorization of the emergency use of certain medical products under certain sections of the Federal Food, Drug and Cosmetic Act, as it was amended or added to by the Pandemic Reauthorization Act of 2013 (PAHPRA).

The provisions in PAHPRA include key legal authorities to sustain and strengthen national preparedness for public health, military, and domestic emergencies involving chemical, biological, radiological, and nuclear (CBRN) agents, including emerging infectious disease threats.

The Washington Post published an article that addressed common concerns about the COVID-19 vaccines. First, it is not just the vulnerable who should get the vaccine. Vaccines protect more than just the person who is inoculated. The more people who are vaccinated means there are fewer people the virus can infect, “lowering the infection rate and the risk for us all.” Another reason is to protect those who cannot get it. The first two approved vaccines were only approved for individuals over the ages of sixteen for the Pfizer-BioNTech COVID-19 Vaccine and 18 for the Moderna COVID-19 Vaccine.

Your decision not to get vaccinated could affect other people around you. Individuals with a weakened immune system may need to rely on the immunity of others to keep them healthy. Not getting a vaccine would be like refusing to wear a mask. We will likely have to wear masks through 2021. In fact, vaccinated people should wear masks and follow social distance guidelines. While the vaccine is effective at reducing symptomatic illness, it is not yet known whether it reduces the likelihood of contracting the coronavirus and being an asymptomatic carrier.

As more people get vaccinated and the US gets to community or herd immunity, there will come a point when we can do away with the masks. “In the meantime, vaccination is a crucial tool. It doesn’t replace other tools but is a powerful measure that can help save lives and help the economy recover.” Allergic reactions can be treated without lasting consequences, but the same is not true for COVID-19. At this time, it is not known what component of the vaccine triggers allergic reactions, but there is not reason for people with food or medication allergies to avoid the vaccine as long as they are monitored in a health-care setting.

All viruses mutate and it may turn out that people will have to receive regular booster shots, like with tetanus or the flu shot. Enough mutations could eventually reduce the potency of existing vaccines. A study of the Moderna vaccine found it was effective for at least 119 days. But some experts believe immunity should last at least a year. “The theoretical necessity of future vaccinations doesn’t override the urgency of getting one now.”

For those worried about political interference in expediting approval, it’s critical to emphasize that no shortcuts were taken in research or the approval process. Vaccine safety was tested in phase 3 trials involving tens of thousands of participants. External committees of scientists vetted the data and produced independent recommendations to support vaccine authorization.

The Allegheny Health Network (AHN) posted a series of frequently asked questions (FAQs) and answers that addressed further questions about the COVID-19 vaccines. The further information there included that no doctor’s order will be necessary to get the vaccine, but you will have to schedule an appointment. AHN said the vaccine is free to all Americans and will be available at retail pharmacies. “Remember, some vaccines require two doses to be effective. It’s extremely important you get both and follow the suggested timeline.”

Who knows where we’ll be with COVID in another twelve months! But there are some things we’ve learned through this pandemic about drug companies and hopefully will continue to insist on. Drug development can be done quickly and safely. Pharmaceutical companies can be open and transparent about their research and allow truly independent, external committees to verify their findings. People can trust the results of drug development when the clinical trial process is not statistically or methodologically manipulated to show what the researchers want to find.

The widespread mistrust of science that became evident during the pandemic seems partly due to the previous manipulation of drug development by the pharmaceutical companies. Like good illusionists, they directed our attention to what they wanted us to see and away from what they wanted to hide. Going forward, open, transparent drug development can restore the trust that is now lacking for the COVID vaccine. During the pandemic drug companies showed they could do COVID Drug Development quickly and safely. We need to remember these things and hold the drug companies accountable to these standards.

01/7/15

Pharma and Its Golden Hoard

© Chrisjeanes | Dreamstime.com - Smaug - The Hobbit Photo
© Chrisjeanes | Dreamstime.com – Smaug – The Hobbit Photo

The debate over the cost of drug development goes all the way back to the late 1950s. The then Chairman of the U.S. Senate’s Anti-Trust and Monopoly Subcommittee said that the pharmaceutical industry had: 1) predatory pricing and excessive margins related to their patents; 2) that extravagant increases in costs and prices were due to large expenditures in marketing; and 3) most of the industry’s new products were no more effective than the ones already on the market. It seems that little has changed over the past fifty-five years.

An often-quoted 2003 study on the cost of drug development by DiMasi et al., “The Price of Innovation,” concluded that it cost an estimated $802 million in 2000 dollars to bring a new drug to market. The 2014 profile released by PhRMA, the advocacy group for the U.S. pharmaceutical industry, estimated that it cost $1.2 billion to develop a new drug. PhRMA noted that: “some more recent studies estimate the cost to be even higher.” In contradiction of the higher R&D estimates of DiMasi and PhRMA, Light and Warburton suggested that: “R&D costs companies a median of $43.4 million per new drug.” This is less than 1/18th of the $802 million estimate by DiMasi et al.

Deciding whose figures to trust can be tricky. For example, Light and Warburton pointed out that the Tufts Center for the Study of Drug Development, where the DiMasi study was conducted, has received “substantial industry funding for years.” Among the concerns they had with the DiMasi study were: inflated costs for drug trials; exaggerated time for R&D; corporate financial risk for R&D was much lower than reported; average costs based on “means” and not “medians,” leading to inflated figures. Using the median trial costs reported by DiMasi (74% of the mean trail costs), they said: “the $802 million figure would have been reduced to $593 million had median costs been used.”

Scott Gavura in “What Does a New Drug Cost” part 1 looked at both the DiMasi study and its critique by Light and Warburton. Gavura said he found the Light and Warburton figure “implausibly small.” In “What Does a New Drug Cost” part 2, he elaborated, saying that he thought their estimates “were based on a sequence of highly implausible assumptions;” the average drug development cost would be higher in the real world. He asked if the low-hanging fruit in drug development is gone. “A growing concern with the pharmaceutical industry is its overall productivity in delivering new drugs.” Gavura concluded his article by stating that he thought criticism of the pharmaceutical industry was justified, if it was done for the right reasons.

Being skeptical of R&D estimates is wise. Data on individual drugs is not transparent, and estimates must incorporate a number of assumptions which have the potential to bias the conclusions.  This lack of transparency fuels suspicion of the process. But we should also be equally skeptical of arguments that dismiss or diminish the growing problems with R&D. There is good evidence to suggest that drug development is a risky, expensive endeavor, and that this work is getting harder.

In a 2008 article published in PLOS Medicine, “The Cost of Pushing Pills,” Gagnon and Lexichin explored the reported expenditures of the pharmaceutical industry and concluded that: “pharmaceutical companies spend almost twice as much on promotion as they do on R&D.”  Their estimate was made from highly reliable sources, one of them being IMS Health, a company relied upon by both the federal government and the pharmaceutical industry for information on the healthcare industry.

Their revised estimates for promotional spending in the US for 2004 was $57.5 billion, twice that of IMS Health. This compares to the $31.5 billion reported by the National Science Foundation for domestic industrial pharmaceutical R&D in 2004. “These numbers clearly show how promotion predominates over R&D in the pharmaceutical industry, contrary to the industry’s claim.”

Allen Frances, the chair of the DSM-IV, has become an outspoken critic of modern psychiatry, the DSM-5, and “Big Pharma.” He reported in Saving Normal that worldwide pharmaceutical sales exceed $700 billion each year. Half of that figure is spent in North America and another one fourth in Europe. Rick Newman reported that Pharma’s profit margin was 16.4 percent, the seventh highest among the industries tracked by Morningside, an independent investment research firm.

The justification of high prices and huge profits by pharmaceutical companies was “mostly fluff,” according to Frances. “Drug pricing has no relation to real cost or value and instead reflects Pharma’s monopoly position in the market and its dominance over politicians.”  At its worst, he said that pharmaceutical research is a “deceptive shell game” meant to seduce and mislead doctors and the public. “The claim that drugs are so expensive because they require so much research is pure smoke screen.”

In The Desolation of Smaug, the final scene shows the dragon Smaug rising up out of molten gold. Goaded by the unsuccessful attempt of the dwarves to destroy him, he flies off to take his revenge on the unsuspecting Lake-town of Esgaroth. Over the past sixty years we have allowed Pharma to gather a golden hoard through its profits from drug development. Like Smaug, Pharma jealously guards its hoard. If we take on a quest to right this injustice, we must be careful not to loose an angry, vengeful dragon upon an unsuspecting humanity by mistake.