Is this product safe? A numbers game

Tomorrow is my day 1 of my adventure – a 10 hour drive to DC. I am looking forward to seeing friends and going on some of my favorite bike rides. I ordered up a week of beautiful spring days without rain and thus far the 10 day forecast looks excellent. Fingers crossed.

Drug safety is a challenging topic that I have been thinking about since my years in Pharma and after yesterday’s blog I decided I wanted to try to tackle it. Prior to my years in Pharma I had the misconception that FDA approval meant that a drug was safe in most people in most circumstances and while that is a simple, reasonable way of thinking about it, the reality is complex. Yet most practicing clinicians do not understand their important role in ultimately determining the safety profile of a drug.

In fact no-one can ever say a drug is safe – this implies that a drug can be used in any person under any circumstance without any chance of anything bad happening. Until a drug has been given every individual who has their own special set of conditions, it cannot be determined to be safe. This is NOT possible. Therefore that best than can be said is that any drug, biologic or device tested has a favorable safety profile.

As I mentioned yesterday, when a company has a new product they want to seek FDA approval for, the company and the FDA meet early in the process to determine how many people the product needs to be tested in and how long the people need to be followed to allow for determination that the product in fact does what it is intended to do (efficacy – it works) and has a satisfactory safety profile to allow it to be sold in the United States. Every country has its own rules and process for this.

The bigger the number of people in the clinical trials and the longer they are followed, the better it is for determining risk/benefit from the FDA perspective. But if these numbers are too high, the expense to the company developing the product may be too high to take the risk. This would mean fewer new products being developed. So there is an inherent tension between companies, the FDA and the public which wants better treatments. Every case is slightly different and for some conditions, particularly rare conditions, the clinical trials may require far fewer participants than common conditions such as diabetes or high blood pressure.

When a product receives FDA approval, a group of government and external scientists have reviewed the data submitted by the company. The external scientists (advisory panel) provide recommendations to the FDA and the FDA makes the decision if the benefit of using this product outweighs the risks. If during the clinical studies, a safety signal emerges in a subset of participants, the product might be approved with warnings that it should not be used in certain individuals or under certain circumstances. This information is communicated to prescribing clinicians through the product label, educational seminars before and after the product is launched, through various persons employed by the company, and a variety of other means.

What I didn’t understand is that in the first several months after release of a new product on the market that new safety signals can start to emerge. The product will be prescribed to a wider variety of persons than were in the clinical trials and uncommon or rare events can only show up after the product is given to large numbers of persons. Active reporting of adverse reactions to new products by the prescribers, pharmacists and patients is crucial to this process. Rare adverse reactions cannot show up until the product has been used in very large numbers of people. In some circumstances it can take years for enough persons with the same reaction to be reported to become a safety signal. Thus some products are on the market for many years and been a great benefit to many persons when there FDA approval is withdrawn and the product is removed from the market. These are tough calls. Sometimes a product may be removed from the market in some countries and not in others. There are no hard and fast rules.

The new safety signal for the J&J vaccine, cerebral venous sinus thrombosis, was discovered in a few months because the was given to millions of persons in a very short period of time. This rare event was identified and FDA and CDC called for a pause for a careful assessment of risk-benefit of continuing to use the vaccine. A difficult decision.

No one can tell any individual that any of the vaccines authorized for emergency use in the US is safe for them or any family member. No one can say that any of the over the counter products we buy and take every day is safe. The best that can be said is that they have excellent safety profiles after being used in millions of persons. For the vaccines, they were used in millions of persons in a few short months. Because of the large numbers of persons vaccinated AND the efforts to encourage those vaccinated to proactively report their experience with the vaccine, I have NO hesitation with being injected with any of the vaccinations currently authorized for emergency use in the US.

If I could do it all over again, I would do better at reporting adverse reactions – even if they were not severe and I didn’t think they were a big deal.