Explaining Drug Safety & PV to Senior Management… and Your Mom!

Jan 27, 2015
Bart Cobert

Pharmacovigilance, Drug Safety and Regulatory Affairs Author & Expert

Explaining Drug Safety & PV

In the course of many years in pharma heading drug safety groups and now consulting, training and doing outreach to the public, I continue to be amazed and humbled by the lack of knowledge by the public about drug safety and what those little pills you pop in your mouth can do.

Except for our small group of drug safety people, very few in the pharmaceutical companies, and even fewer in the medical world (MDs, nurses, dentists and to some degree pharmacists), have any idea about the safety of medicines. The public has no idea whatsoever about the safety of medicines.

I preface this because I was once again shocked this month when I delivered a talk at a Science Café session sponsored by our local university entitled: Medications, Drug Safety and Side Effects: Great Expectations or Bleak House. (See ScienceCafes.org for information about the wonderful Science Cafés around the country. These are talks by scientists for the lay public often sponsored by local universities or science societies on current and interesting science topics. Often held in a restaurant or bar – the concept of hearing a science lecture with a beer in your hand munching on hot wings is wonderful).

The audience was non-medical but bright, educated and interested. I reviewed briefly the concepts of ADME (absorption, distribution, metabolism and elimination/excretion), how a drug is approved by FDA (pre-clinical, phase I-IV studies, post-marketing PV), what “side effects” are, how causality is done (or not done), drug interactions and how we cannot predict them too well, etc. The talk was very well received but was somewhat shocking and even upsetting to people who now realized that “safe and effective” means the benefits outweigh the risks in the appropriate patient population at the appropriate dose, etc. and not a blanket guarantee of great efficacy no side effects.

So that made me think again about how to convey the ideas and concepts about DS/PV to different audiences: The first is the group of people who don’t know about the pharma world or industry at all: the public. The second is those in the pharma world who don’t do DS/PV and have only a vague idea at best of our functions and duties.

First, to the public:

It may be the best policy to assume that this audience (whether you are speaking to them at a meeting or writing or using social media, etc.) does not have any idea about where their pills and medicines come from. They have no idea what the FDA is, who works there, how drugs get to the market, what “safe and effective” really means and how “side effects” are collected.

Some points to make include:

  • The FDA is a group of scientists who tightly oversee drugs and devices. Oversight is less stringent for cosmetics, health foods, supplements and even some OTCs. The companies must/should monitor their products themselves.
  • Many people don’t even know what we mean by “labeling” and how the Package Insert is created and how “solid” it is.
  • Generic drugs are handled somewhat differently from branded drugs at least in terms of the labeling.
  • Most drugs or drug product come from India or China.
  • All drugs can produce side effects. Don’t use the words “adverse events” or “adverse reactions” and don’t get into the distinction between these two. People’s eyes will glaze over. Use the words “side effects” which everyone understands.
  • More is not always better in terms of dosing and may increase the risk of side effects.
  • Even if you’ve taken a drug for years, it can still produce side effects.
  • When a drug first comes on the market very few patients have been exposed to it. Perhaps several thousand but often only several hundred. It takes years for a more complete side effect profile to become known.
  • In fact, a drug’s side effect profile is never fully known. New side effects, interactions, etc. can be discovered years or decades after the drug is first launched.
  • Some drug side effects can be predicted: Take too much of a drug for hypertension and your blood pressure may go so low you pass out. Not a surprise. Many side effects cannot be predicted and can occur “out of the blue”. They are unpredictable.
  • Some truly weird side effects can occur and are usually unpredictable. The classic story of DES (diethylstilbesterol) in which vaginal cancer occurred in the daughters of the women who took the drug years before is a fine example. This was something no one could have predicted or even imagined.
  • After marketing, most drugs have side effects collected using the voluntary reporting system. There is no obligatory side effect reporting except by the pharma companies. This system works but can take a long time. It is changing as we move to electronic health records, the Sentinel Initiative and “big data”. Many people find this hard to believe.
  • Genomics as a predictor of side effects has been disappointing so far but it is still in its infancy.
  • Drug-drug interactions (you have to briefly explain this) are often unpredictable and are almost always unpredictable if one takes more than two drugs.
  • The labeling/package insert gives the best known data (usually) but usually indicates that many side effects have been reported but it is unclear if they’re really due to the drug.
  • The ability to determine causality is very limited for individual side effect reports. I often give the hypothetical (maybe not so hypothetical) example of a 65 year old hypertensive, diabetic, obese person who never exercises, has an elevated cholesterol and whose parents died of heart disease in their forties. This person starts a new drug and a week later has a heart attack. It may be impossible to establish whether the drug caused the myocardial infarct. The patient had almost all of the risk factors for an MI.
  • Each person can react differently to a drug.

Second, to our pharma colleagues not in DS/PV:

Avoid excess jargon, abbreviations and acronyms, particularly with non-medical folks (lawyers, marketing, sales, etc.). Depending upon the audience and time available, you may want to do a brief review of why DS/PV must be done, drug risks, how we do PV and possible consequences of safety issues (even when PV is done totally correctly).

Things you can point out:

  • The company, including marketing and sales, must report to PV all AEs and SAEs received worldwide. It’s the law in the US and pretty much everywhere else where drugs are sold or studied in trials. Written SOPs are also required. If you don’t have SOPs, put them in place immediately.
  • There are penalties for non-compliance of PV including drug withdrawal, strong changes in labeling, loss of the NDA/MA, monetary fines and even prison for egregious violations. In the US, point out the “Park Doctrine” which has been used to imprison some pharma people and others for covering up safety problems. If you are unfamiliar with this, google it.
  • The job of DS/PV includes protecting the company and the products. However, you may want to define “protecting” to mean that the medical and scientific safety profile of the products must be continually tracked to ensure that the products get a fair and correct safety review at the FDA and other health agencies. It certainly is NOT to hide, cover up, minimize or ignore safety issues. The job of DS/PV (as well as that of the company) is to protect the public health in addition to selling products.
  • For large companies and/or companies that sell or study in more than one country, safety handling is now extremely complex. Regulations and requirements are increasing as more and more countries are getting more deeply involved in DS/PV.
  • Failing to do good safety reporting can jeopardize new drug approvals if the health agency doesn’t fully trust your company.
  • We in DS/PV are well aware that the job of the company is to sell product, which pays everyone’s salaries!  We are not the “sales prevention group” but are here to help the company do the right thing and obey the rules.
  • DS/PV also realizes that AEs, especially SAEs, can be “hot potatoes” and that anyone in the company who receives an AE/SAE should send them immediately to DS/PV where they will be appropriately handled. DS/PV will work with everyone in the company to make sure that this occurs smoothly and with minimal interference to the rest of the company. That is, get us the data and we will handle it from there.
  • DS/PV is also ready, willing and able to help in safety crises. Although they hopefully won’t occur, one never knows.
  • The company should expect audits and inspections from FDA, EMA/EU member states and others and we will be ready for that.
  • The flip side of the coin here is that DS/PV must be adequately resourced to do its duties. DS/PV, like every other department in the company, will be fighting for resources, personnel and funding.
  • It is useful for DS/PV to keep and track data not only to justify budget requests but also to track quality and compliance. This can include, AEs and SAEs received and processed, expedited reports, periodic reports, safety queries form agencies, cases handled per DS/PV processor etc.

Bottom Line:

DS/PV needs continual outreach both to the public and within companies for multiple reasons. You should be prepared for this.

 

 

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