are drug regulators for hire asks Dr C

 

....,,,,............']

  Bmj article here

.

]From FDA to MHRA: are drug regulators for hire? BMJ 2022; 377

 

 

(Published 29 June 2022)

 

Patients and doctors expect drug regulators to provide an unbiased, rigorous assessment of investigational medicines before they hit the market. But do they have sufficient independence from the companies they

are meant to regulate? Maryanne Demasi investigates Over the past decades, regulatory agencies have seen large proportions of their budgets funded by the industry they are sworn to regulate. In 1992, the US Congress passed the Prescription Drug User Fee Act (PDUFA), allowing industry to fund the US Food and Drug Administration (FDA) directly through “user fees” intended to support the cost of swiftly reviewing drug applications. With the act, the FDA moved from a fully taxpayer funded entity to one supplemented by industry money. Net PDUFA fees collected have increased 30 fold—from around $29m in 1993 to $884m in 2016.1 In Europe, industry fees funded 20% of the new EU-wide regulator, the European Medicines Agency (EMA), in 1995. By 2010 that had risen to 75%; today it is 89%.2 In 2005 in the UK, the House of Commons’ health committee evaluated the influence of the drug industry on health policy, including the Medicines and Healthcare Products Regulatory Agency (MHRA).3 The committee was concerned that industry funding could lead the agency to “lose sight of the need to protect and promote public health above all else as it seeks to win fee income from the companies.” But nearly two decades on, little has changed, and industry funding of drug regulators has become the international norm.

note this article is one year old. 

 

the language of pain

Are generics safe? Zantac the latest problem

BBC reports on Zantac/Ranitidine recall.

article is lousy: Gives no reason and points no fingers, nor does it say if it is only generics or the brand name.

Bloomberg says it is made in China and India.

In the meantime, the Italian Drug Agency said last week it was ordering a recall of all versions of Zantac made with active ingredient from Saraca, the Indian manufacturer. Italian regulators also banned the use of some types of Zantac produced by other pharmaceutical companies pending analysis of the drugs.

Bloomberg has an article on the problem of generics.

this photo pretty well says it all:

the article discusses the contamination of Valsartan and other ACE2 inhibitor type BP meds.

Companies conduct clinical trials in humans over several years to prove a drug is safe and effective. But 90% of all medications prescribed to Americans are generics. They’re cheaper, they’re supposed to work the same way, and they receive less scrutiny right from the start. Companies manufacturing generic drugs have to show only that patients will absorb them at the same rate as the name-brand medications they mimic.At least 80% of the active pharmaceutical ingredients, or APIs, for all drugs are made in Chinese and Indian factories that U.S. pharmaceutical companies never have to identify to patients, using raw materials whose sources the pharmaceutical companies don’t know much about.The FDA checks less than 1% of drugs for impurities or potency before letting them into the country. Surveillance inspections of overseas factories have declined since 2016, even as the agency is under pressure to get more generics to market more quickly.

the article goes into a lot more detail about the Valsartan contamination and about China's growing pharmacy manufacturing business, but the clue is that the company switched to a different solvent, which was cheaper. Then other companies read the patent application and figured they too could make the drug cheaper and voila, many sources of the BP medicine also produced contaminated medicine.

Corruption in the Chinese pharmacutical industry

from StrategyPage. the article is about China's economic and military status but contains this:

The increased censorship and restrictions on what the media can report go beyond the economy. Corruption and fear of embarrassment also play a role. Current examples are how the secret police are handling Chinese victims of yet another “dangerous food and drugs” scandal.

Many of the victims of Changsheng Biotechnology, the second largest supplier of vaccines in China, are seeking compensation from the government for injuries suffered from bad vaccines.

In July Changsheng was accused of selling unsafe medicines and getting away with it by bribing government inspectors to ignore evidence of poor quality control that resulted in ineffective vaccines.

This is the latest of many such scandals involving dangerous food products or medicines. It is why the government has been so energetic in its anti-corruption campaign but also evidence that the “war on corruption” was not going as well as the government was reporting.

This latest incident was so scary that even North Korea refused to buy low cost medicines from China because of the growing popular belief (in China and North Korea) that too many Chinese made drugs were probably ineffective.

Homones and trans

I had to take hormones for endometriosis.

the pill made me depressed.

The stronger medicine with androgenic properties made me "fat hairy and horny"... luckily I couldn't afford the full dosage or I would have gone manic and started to attack men.

The final medicine I took turned off my hormones and made me severely depressed. I cried all the time.

(So when I had men with prostate cancer who were put on this hormone, I warned them. I wonder how many of them ended up committing suicide? Or drinking for depression etc)

The emotional side effects of birth control pills are rarely discussed, but then as a woman with ovarian problems, I can tell you my own hormones did the same thing. PMS anyone?

I could tell my period was due when I would cry over nothing.

In the good old days, men with prostate cancer often were placed on estrogen: Cheap and efficient. Why did we stop using this? Because a double blind study showed the death rate on estrogen was higher for men: Not from cancer, where the death rate was lower, but from cardiovascular disease.

So this article (Via Virtueonline, an Episcopal webpage) notes the dirty little secret that no one wants to discuss, lest they enrage the twittermob or lose their job:

Hormones for transsexuals have side effects.

The US study compared medical records of over 5,000 transgender people against more than 97,000 others. It also suggested that men who took hormones for more than six years were ten times more likely to have a stroke caused by a blood clot than the general population. 'Risks' The study concluded: "These results may indicate the need for increasing vigilance in identifying long-term vascular side effects of oestrogen therapy". Senior author Michael Goodman of Emory University's Rollins School of Public Health said the findings could be "taken into consideration when planning follow-up and evaluation of patients". "The confirmation of this risk is good to have so patients can be warned", added fellow author Dr Joshua Safer.

this, presumably, was in adults.

The problem of giving various hormones and puberty blocking hormones to young teens with "gender dysphoria" is a bigger problem, because not only do many if not most of these kids have merely a transient wish to change sexes, and change their mind later, but the long term health problems are not clear.

and not in the article:

the lowering sperm count is back in the news.

NYTimes article.

it discusses the drop in sperm count over the last 40 years, but actually it has been decreasing since the 1930's.

Estrogen in the water supply? Including phyto estrogens from plastics and herbicides and plants?

Chinese generic medicines and fake/counterfeit drug dangers

this is a big problem here: generics are cheaper but you don't know if they work.

Usually, if it is a major infection or something important, I buy brand names or brand name generics at Mercury drug store, which checks on their generics.

The cheaper generics? I use when not so important.

Once Lolo had an infection that didn't get better with generic cephalexin, and our niece said to get the brand name, and the infection promptly resolved. Since he had CLL and a poor immune system, this could have mean a life threatening infection: but the generic was not completely fake, so it merely kept the infection under control with a suboptimal dosage.

Generic drugs and the Clinton foundation

Like a lot of "charitable Trusts" (or like the Vatican for that matter), the Clinton foundation is probably doing good while supporting a lot of hucksters.

Charles Ortel writes about that here. I don't understand much of it, being an economic/financial illiterate, but this part I do know something about:

How did Deputy Attorney General Rod Rosenstein, while U.S. attorney in Maryland, miss the fact that the Clinton Foundation was promoting use of potentially adulterated HIV/AIDS drugs from October 2003 forward, even as he took until May 2013 to help win a $500 million set of penalties against the Indian manufacturer of the generic drugs?

there has been a big push to let people use "generics", but the dirty little secret is that a lot of Chinese and Indian companies don't have the quality control standards of western companies, and what is worse, a lot of them adulterate the medicine or even push counterfeit medicine that doesn't work as the real thing.

To make things worse, they underprice western companies, meaning that now even brand name drugs might be made overseas: The heparin scandal, where a cheaper chemical was added to the heparin so that it could pass the testing phase but didn't work and killed a few people is the tip of the iceburg.

Fake antibiotics and anti malarials are the cause of many deaths in poor countries, as the linked article goes into the many ways and problems with generics. And since people often die despite the best treatment, one can see how deaths can be overlooked or hidden, especially in rural areas or the slums of poor countries.



and then you have the "cough medicine" deaths because they added antifreeze as a cheap sweetener to cough medicine, and killed at least 100 people in Central America. 

after "activists" condemned "big pharma" for opposing the use of generic medicines for HIV, Bill Clinton's push to get the generics was hailed... but not really examined closely.

Generics from Canada

I am old enough to remember when importing cheap generic drugs from Canada into the US was a big political controversy.

I am posting the stories below just for my own information, in case there is a conspiracy behind these deaths:



Read this story in the UK telegraph: Canadian pharmaceutical founder and wife dead in suspicious circumstances.

This old 2010 story at the NYTimes notes that their generic medicines have problems with quality control. One of their products is a fentanyl patch without gel: presumably not as easy to abuse.

and a 2014 story says they were suing Canada for not letting them import their drugs that were made in India.

and this older article notes they were helping supply cheap HIV medicines to Africa but found the red tape was so expensive they didn't plan to continue. More here about the problem of intellectual property and trade rights in the Canadian generic drug companies trying to supply medicines to third world charities.

or is it because they are in trouble for stealing trade secrets from another drug company? Philly.com has the story of the big lawsuit over this.

WtF: Information on smoking a non-gel Fentanyl patches?... I was aware of the abuse but not that the powers that be allowed addicts place these discussions on the internet.

medical article on the problem.

so for conspiracy folks, we have sex, drugs and, well maybe not rock and roll but business shennanigans.

And of course, mentioning HIV drugs to Africa being in the conspiracy of Arkancide.

Yes, I am being sarcastic.

substandard, contaminated, and even counterfeit drugs are a big problem here, so I will keep an eye on it.

Beethoven and Ancient Rome and lead

There is actually a Wikipedia site on Beethoven's death, that includes his autopsy findings..

The autopsy revealed a severely cirrhotic and shrunken liver, of which ascites is a common consequence. Scholars disagree over whether Beethoven's liver damage was the result of heavy alcohol consumption, hepatic infection, or both.

Yup. I've treated lots of these folks. Mainly in heavy drinkers. He also had evidence of a shrunken pancreas, suggesting pancreatitis.

but at the end of the article they insist he died of lead poisoning.

In 2010, Dr. Andrew C. Todd, of the Mount Sinai School of Medicine in New York City tested two pieces of Beethoven's skull for lead, and determined that the concentration of lead was no greater than would be expected for a normal man of 56 at that time.^[16]

The leading cause of death still remains lead poisoning however. M. H. Stevens and his team have concluded that high levels of lead deep in the bone sampled from Beethoven's skull suggest repeated exposure over a long period of time rather than limited exposure prior to the time of death. Among other evidence, the finding of shrunken cochlear nerves at his autopsy is consistent with axonal degeneration due to heavy metals such as lead. Chronic low-level lead exposure causes a slowly progressive hearing loss with sensory and autonomic findings, rather than the classic wrist drop due to motor neuropathy from sub-acute poisoning. Beethoven's physicians thought that he had alcohol dependence

So where did he get lead? Yes, it was used as a medicine, but one overlooked reason for lead is that it was used as a sweetener in cheap wine.
Wikipedia article here on how this was done.

They were made by boiling down grape juice or must (freshly squeezed grapes) in large kettles until it had been reduced to two-thirds the original volume, carenum; half the original volume, defrutum; and one-third, sapa. The main culinary use of defrutum was to help preserve and sweeten wine, but it was also added to fruit and meat dishes as a sweetening and souring agent and even given to food animals such as suckling pig and duck to improve the taste of their flesh

Smithsonian article discusses.

Lead acetate, also known as sugar of lead, is a salt that (ironically) has a sweet flavor—a fairly unusual quality in poisons, which are more likely to taste bitter, signaling to the taster that they are unsafe for consumption. The ancient Romans used the compound—which they called sapa—to sweeten wine, and the aristocratic segments of the population could toss back as much as two liters a day (about three bottles’ worth, although wine was usually diluted with water). There is debate as to whether the wine alone could have produced the traditional physiological effects of lead poisoning, such as organ failure, infertility and dementia—the little things that help facilitate the fall of an empire. 

this article discusses lead in Roman times. It was recognized as a poison, since those working with lead tended to get sick.

The irony of lead pipes is not that they could cause lead poisoning, but that hard water deposited calcium on top of the lead. This means all those stories of lead poison from their pipes might be exaggerated: The lead was covered... except when they cleaned them out..

deposits of calcium carbonate in pipes and aqueducts protected against corrosion and insulated against the introduction of lead. With no taps to shut off, water flowed continuously and so would not have been in prolonged contact with the metal. Most water brought to Rome by its aqueducts was used, in any event, to supply its public baths.

but wine was sweetened by boiling it down... in lead vessels. And some used lead pots.

Like modern folks who have gotten acute lead poisoning from drinking acidic wine in pewter or ceramics with high lead content, the lead could cause problem.  The article gets into discussing lead vs copper vessels, and then calculates the dosage... or not. Long technical discussion there.

Science magazine discussion of lead poisoning and Rome. Yes, there was lead, but not enough to cause problems.

The researchers compared the lead isotopes in their sediment samples with those found in preserved Roman piping to create a historical record of lead pollution flowing from the Roman capital. Tap water from ancient Rome likely contained up to 100 times more lead than local spring water, the team reports online today in the Proceedings of the National Academy of Sciences. While the lead contamination was measureable, the team says the levels were unlikely high enough to be harmful, ruling out tap water as a major culprit in Rome's demise.

so what about the skeletal evidence? 

As far as I know, the first and only study to actually measure levels of lead in skeletons from Rome is the one that involved my samples from the two cemeteries of Casal Bertone and Castellaccio Europarco (1st-3rd c AD).... 

 What you can see is that there are fairly low levels of lead in the pre-Roman periods in Britain (Neolithic, Bronze Age, Iron Age) and the levels are lower in the post-fall of the Roman Empire (after 5th c AD).

... no one in the pre-Roman period is getting poisoned. The Imperial period is pretty special - we've got a person with lead levels over 20 mg/kg, which is 20 times higher than modern recommendations! In fact, this level is two times higher than the level the WHO considers "very severe lead poisoning."

the problem? Sample bias. It is not known if the sample was evidence of lead poisoning in the entire population.

water supply contamination continues to be a problem: in 2004, high lead levels were found in some neighborhoods of WashingtonDC.

find your state here if you want to know if there is a problem.

we still see kids with lead poisoning from old paint: The peeling paint chips are sweet and eaten by toddlers who place everything in their mouths. Since these paints now are forbidden, such cases are much less common, except in older buildings.

of course, nowadays one doubts anyone is using lead acetate to sweeten anything.

But back in 2008, there were a couple dozen acute cases in Germany from smoking marijuana: Some dealers added lead powder to their stash to make it seem heavier than it actually was to make a bigger profit.

Lead acetate has to make meth:

Acute lead poisoning is another potential risk for methamphetamine abusers. A common method of illegal methamphetamine production uses lead acetate as a reagent. Production errors may therefore result in methamphetamine contaminated with lead. There have been documented cases of acute lead poisoning in intravenous methamphetamine abusers.

But lead as a sweetener is not something used nowadays, because there are a lot of other cheap artificial sweeteners that can be used instead.

we get reports of fake sweeteners all the time here, but it is usually cyclamate, which is not very toxic.

However, the real worry is if old fashioned anti freeze is used.

Luckily for folks, the Austrian wine scandal using this chemical was detected by the Germans quickly.

Not all such contamination has been found easily, nowever.

here have been quite a few deaths from Chinese medicines that used Antifreeze to sweeten them.

NYTimes 2007 article about that scandal

Agatha Christie, call your office.

Opiod epidemic: is it from doctors giving pain pills?

CDC report. of a survey

A total of 1,294,247 patients met the inclusion criteria, including 33,548 (2.6%) who continued opioid therapy for ≥1 year. Patients who continued opioid therapy for ≥1 year were more likely to be older, female, have a pain diagnosis before opioid initiation, initiated on higher doses of opioids, and publically or self-insured, compared with patients who discontinued opioid use in <365 days 

so the numbers are high: But the percentage is actually quite low.

and they don't include the question WHY the medicines were used:

. Third, information on pain intensity or duration were not available, and the etiology of pain, which might influence the duration of opioid use, was not considered in the analysis. 

and after a long analysis they note the elephant in the room:

Finally, prescriptions that were either paid for out-of-pocket or obtained illicitly were not included in the analysis. 

a lot of "prescription drug abuse" is from stealing medicine, or buying it on the street, but never mind.

momjones article here 

Conventional wisdom holds that overprescribing is fueling the epidemic: Someone injures himself, is prescribed painkillers, and quietly develops an addiction. But that's not the whole story: According to federal data, most people start out by taking the painkillers of a friend or family member. The best predictor of prescription opioid abuse is a history of other drug abuse, according to a recent study in Addictive Behaviors. Experimentation typically starts during adolescence or young adulthood.

and only a small percentage get them from doctors (36%). One wonders if a lot get them from "pill doctors" who give out thousands of them for any reason, but again that is not the question.



more data here.

92 percent of people do not abuse drugs of any sort.

and one wonders about the definition of "misuse". Probably they mean not prescribed by a doctor for that episode:

Among people aged 12 or older in 2015 who misused prescription pain relievers in the past year, the most commonly reported reason for their last misuse of a pain reliever was to relieve physical pain (62.6 percent), which is the reason pain relievers are prescribed (Table B.11). Even if the reason for misuse was to relieve physical pain, use without a prescription of one's own or use at a higher dosage or more often than prescribed still constituted misuse.

ditto for other drugs: it might not be "abuses" but "self medication".

As for the hype that the drug companies pushed narcotics for pain: Why, yes.

Most of the "assisted suicides" by Dr Kavorkian were in patients with uncontrolled pain. Hospice doca and those in pain clinics started using narcotics in contolled amounts because they had fewer side effects than other medicines. (NSAID mainly, which cause GI bleeds, heart and kidney problems).

If you get rid of the pain, most people can simply be withdrawn from their narcotics slowly. Some like the mild buzz from them and continue, so that is abuse. And others aren't in pain but steal/borrow or take them to get high.

The 1960's idea of getting high (along with normalizing marijuana to get high) is the precursor for the idea that if you feel unhappy that drugs will make you happy.

This is a social problem, and the cure is religion.

But that is another story for another time.