Three seemingly unrelated issues in the news that touch marginally or not at all on drug safety nevertheless carry important lessons for those of us who do pharmacovigilance for a living.
1- Meningitis from injectable steroid preparations made by a compounding pharmacy. As of this writing, over 20 people have died apparently from fungal meningitis attributed to vials of drug produced by a Boston area compounding pharmacy. The FDA has released a list of some 2900 medical centers and individual health care providers who may have received and used the products. The compounding pharmacy has done a voluntary recall of all of its hundreds of products. Lawsuits have already been filed. A google search using the three key words: “meningitis steroids lawyer” produced 729,000 hits and at least two firms had paid aids seeking patients for a free consultation on this issue. Patients are showing up at ERs concerned with and without symptoms. Anyone who received a steroid injection during the critical time period is concerned or scared. Diagnosis will be hard and may take a long time.
The finger pointing has begun with disputes over jurisdiction (FDA vs state governments), good manufacturing practice (GMP) oversight, whether some group or groups obstructed the FDA investigations and more.
2- The NY Times reported on October 22, 2012 that “Five people may have died over the past three years after drinking Monster Energy, a popular energy drink that is high in caffeine, according to incident reports recently released by the Food and Drug Administration.” The Times correctly notes that “these reports do not prove a link between Monster Energy and the deaths or other health problems.” Nonetheless, lawsuits have been filed; the company is ““unaware of any fatality anywhere that has been caused by its drinks” and the stock price has dropped.
This will now wend its way for years through the courts, the media, interest groups and the internet. Where the truth lies and when it will come out remains to be seen.
3- In Italy, six prominent engineers and scientists and an ex-government official on a scientific committee were convicted of multiple manslaughter for having provided “inaccurate, incomplete and contradictory” information about the danger of the tremors felt ahead of a 2009 earthquake in L’Aquila Italy that killed 309 people according to the BBC (https://www.bbc.co.uk/news/world-europe-20039769). The committee had said that a major quake was not impossible but not likely. They were sentenced to six years in prison. The scientific community and media are aghast and appalled. One prominent physicist said he would not now take such a job.
They clearly got it wrong, tragically wrong. Evidently predicting earthquakes is about as easy as predicting….well…. adverse events.
So how does this tie into drug safety and what lessons can we learn?
Well, item number one, the contaminated steroids really is a drug safety issue though it is somewhat more than that. Some as of yet unanswered questions:
- Were the products manufactured under GMP?
- Did they even have to be manufactured under GMP and if not why? If yes, what happened?
- Did the companies/pharmacies have to report AEs and/or manufacturing issues to the FDA or local agencies? If yes, what happened?
- How did the companies handle drug safety and product quality issues? Did they have (good) SOPs?
- How did three (as of now) different fungi contaminate the products? Or did they? Was it an issue of manufacture? Transport? Storage at the sites?
- How did management handle the situation (see the Park Doctrine)?
- Did the companies have prescriptions for a patient for each product shipped as, apparently, they had to have? Or did they not have to have a prescription in each case?
- The NY Times on October 22, 2012 reported that complaints of product problems date back to 1999. What was done?
- Who will pay the monetary costs for all of this?
So now the fingers are pointing; everyone is lawyering up; there are embarrassed government officials in Washington and the state capitals running for cover; there will probably be Congressional investigations and surely a new law putting these companies under FDA oversight equal to that of drug companies.
This is tragic for those who died and a catastrophe for those who may go months now wondering if they will have fungal meningitis or some other injection related problem. Many will undergo tests that, hopefully, will not hurt them too much to see if they have meningitis. For those in the industry, there will be job losses, bankruptcy, suffering, lawsuits, perhaps prison, more bad publicity and more.
This is, in fact, a rather standard drug safety story that we have seen happen after many other products. All of these stories are messy and ugly and will get messier and uglier.
Item number 2 is not a drug (apparently) but rather a supplement. The labeling for supplements generally lists the contents and amounts (which here include caffeine). The company and the American Beverage Association note that “the ingredients and labeling comply with all US FDA requirements.” (https://www.fox23.com/webmd/story/FDA-5-Death-Reports-for-Monster-Energy-Drink/Z6p2tWDfSkai6jW0IcNf5Q.cspx).
So here we have beverage that evidently complies will all FDA requirements but which has been associated with deaths. Causality has not been established and it looks like it will be the courts (and perhaps health agencies) that will decide. One would not be surprised if lots more cases now pop up as the publicity will increase awareness. How the company and FDA will handle these remains to be seen also.
Item 3 is clearly the “one that doesn’t belong in this group”. Italian earthquakes and drug safety? The issue here is that predicting earthquakes is evidently as easy (read: very hard) as is predicting drug side effects. Evidently even tremors before the quake are not necessarily predictive. Sound familiar? Do all elevations of liver function tests predict subsequent severe liver toxicity? (No). Yet well-intentioned, senior scientists got it wrong and are now being sent to jail.
What conclusions do we draw about drug safety?:
- Bad things can occur at any time in a seemingly random way for a drug, a beverage, an OTC, a device etc. People can be hurt and die from what look like innocuous or even products that seemingly are good for your health.
- Bad outcomes make everybody unhappy and fuel anger, grief, lawsuits, punishment, revenge, bankruptcy, personal agony and even death.
- Blame must be placed; somewhere, somehow, some way.
- Being a senior professor, a respected medical professional doesn’t matter and may even make it worse.
- The folks lower down on the food chain will suffer too.
- Even if it didn’t look like the law applied to you, in retrospect someone (everyone maybe) will say it did.
- When the material hits the fan, you will be all alone.
So what should you do (in my opinion):
- Companies that must do drug safety should obviously do drug safety and do it well.
- Even if you don’t have to do rigorous safety and toxicity trending and reporting, maybe you should do it anyway as a good corporate citizen.
- All manufacturing of products that go in, on or even near the body should be manufactured in a meticulous way all the time. Product quality must be job one (and two and three…). Companies should do (and document) GMP even if they seemingly don’t have to. Constant vigilance is necessary.
- Senior executives should be aware of the Park Doctrine (we’ll talk about this in a later post).
- Those lower on the food chain in companies and organizations should always do the right thing even if the management says (or rather implies) that you don’t have to 100%.
- If you don’t know how to do the right thing or even what the right thing is, find someone or some organization that does!
- If you are pushed or forced to do the wrong thing, well, you have a moral and ethical dilemma. Obviously one should always do the right thing but mortgage payments and other mundane daily life issues often cloud up this judgment.
- Don’t interfere with a governmental investigation. If FDA or a government agency wants something, give it to them unless there is some extraordinary reason not to (not sure I can actually think of any right now).
- When the bad things occur, don’t dribble out the bad news in the hope that it will go away (ever hear of newspapers, the media, the internet, Facebook, going viral?). Get an expert on crisis management and damage control but do the right thing.
- Remember that nothing stays local that the FDA talks to the Canadian, EU and other agencies (who go on the internet too) and that when it rains it pours.
- Individuals in the organization who are not involved may be hurt as collateral damage even though they had nothing to do with the issue at hand. Have a Plan B ready if you can. Keep your CV up to date at the very least.
- Keep up on what’s going on in your industry and job area.
- Understand you are in a high risk profession. Be skeptical. Trust but verify.
- Even if you do the right thing, bad consequences and outcomes may occur. Life is not fair.
- Sometimes the glass is not only half empty but cracked and leaking.
And finally, to repeat, always do the right thing (After you figure out what the right thing is – it may not be so easy).
