Risk identification in PSUR

What is the point of identifying risks?

To minimize them. And one way to minimize risks is by informing the public about them. Raising awareness is our ultimate goal. The SmPC and PIL have to contain equal information and be truthful to the medicine’s actual safety profile.

If you identify a potential risk that is nowhere to be found in the SmPC, you find yourself in front of a dilemma. However, if a regulatory authority doesn’t identify a risk as important, if they give no recommendation on the matter, follow their judgment.

I.  The process of determining risks

Check risks identified by the relevant authority

Risks identified by an official Regulatory authority make this process far easier. Look up information on the CMDh to see if you have the risks available. However, in some cases they aren’t, which can complicate things.

Detect information in the SmPC

Go through the SmPC and detect information that you will include under Important identified risks, Potential identified risks or Missing information.

Important identified risks

These are easier to identify, as, usually, it’s specifically written that a certain molecule has a certain identified risk. Hypersensitivity is one of the most common identified risks due to the interindividual differences among the patients.

Potential identified risks

Unlike Important identified risks, Potential identified risks fall into an ambiguous grey area. These include risks on the level of a whole group, not just your medicine in particular.

Sometimes, there is a reported risk for one medicine that belongs to a specific drug class, but it’s not reported for the class as a whole. If your substance of interest is a part of such drug class, this makes it a potential risk for your substance as well.

Identifying potential risks is a very complicated area to master, filled with pitfalls and nuances to look out for.

Missing information

The only part of the section that can be filled out without a doubt. The SmPC clearly states “There is no information” or “Information missing” for certain characteristics. Most often, the missing information is related to children, pregnancy, lactation etc. Some drugs are never tested on sensitive groups, thus making their effect unknown.

Always follow the same order. Start with important identified risks, in the order listed in the SmPC. Then, continue to potential risks. Finally, write down the missing information.

II. Writing the Risk section

Don’t summarize or unnecessarily duplicate information you already presented in previous sections. Instead, provide an interpretation and critical appraisal of this information.

Characterize risks

Thoroughly cover each risk. You have to break down and analyze what fundamentally makes it a risk. This is done on the basis of the literature accumulated for the PSUR. See what adverse events have been reported for a given substance, and comb literature findings for their mentions.

Present the risk in light of the bigger picture and what it means to the well-being of patients. Also, write how did you communicate the risk, and in which sections of the respective product information.

Sympto® is quite useful when characterizing risks, as you can utilize it to search through your literature findings and case reports to support the risk claims for the respective medicinal product.

Not only does Sympto’s extensive filters make it easier to grasp the exact magnitude of a certain risk, but you can also use its “Signal Detection” feature to define the statistical meaning of an adverse reaction (as found in your database) linked to a given risk.

Writing about risks

• Write how you communicated this risk, and in which sections of the respective product information.
• Thoroughly cover each risk with appropriate literature findings (base your argumentation on literature, cases and studies included).
• Elaborate why a specific risk is identified as a risk.
• Rely on your SmPC. Here more than ever.

Weigh medicines in the balance

It all comes down to the risk-benefit balance. We strive to decrease the risk, and increase the benefit. When we assess the benefits and risks, we assess what a drug can do for a patient’s well-being. And this is always very individual for each medicine, and each patient.

Find out as much as you can

Investigate on the Internet to find out more about the topic at hand. Look up what has been previously discovered about it. When you search for information on a risk, don’t limit yourself by a time period. Trace back everything written about a risk linked to the medicine you’re working on.

When the lines are blurred

Sometimes the lines between potential and identified risks are blurred. It can become complicated to sort a risk. It’s a collaborative task, with combined input. Every time, you have to start again. Analyze and compare. Has somebody already identified this risk and does it show discrepancies with your SmPC?

In these cases, you have your SmPC and your medical judgement. If your SmPC relates to the generic drug, it has to be faithful to that of the originator. It relies on your own critical judgment and that’s what makes this segment the hardest in PSUR writing.

When an important risk is identified as potential

Sometimes, a risk you believe is identified was sorted as potential according to the CMDh, maybe because the wording of another SmPC’s 4.8 section is slightly different from yours.

The GVP advises you to use risks prescribed by the CMDh. However, they may not be noted as risks in the originator’s information. In these cases, use your medical judgement and the SmPC to determine where to sort these risks. Make the decision and stand behind your assessment.

The voice of authority

In some situations, a regulatory committee such as PRAC issues recommendations to classify an adverse effect as “rare”, then it automatically becomes an identified risk.

And here we have a problem – what if we find a risk in the period when it’s not yet included in the medicine’s respective SmPC? Still, you have to sort it under Potential risks, as it has not been included in your SmPC as of yet. This is specific to PSURs and the Addendum to the Clinical Overview. Sometimes newly discovered risks are not yet mentioned in the product information at the time you write them.

Maybe the regulatory authorities will issue information after your data lock point. Then it could happen that you are not obliged to change the information in your PSUR. It all depends from one specific case to another.

Learn from feedback

Look through previous verdicts. What was omitted? What wasn’t included last time? What should you include?

Screening PSUSA verdicts and already assessed PSURs is a good way to hone your judgment. Before your first PSUSA verdict, however, you have only your critical judgment and logic.

Always go section by section to check if everything you wrote about your risks is in order. With good preparation and organization, your risk identification becomes a foolproof process.

Want to read more about the specifics of PSUR writing? We’ve got you covered. Take a look at our article on the Literature section, or check out how good preparation can make your PSUR composition more efficient.