Overcoming Global Drug Safety Operations And Safety Reporting Challenges

Does safety reporting get the attention it deserves?

In our hearts, keeping patients safe is the number one priority of investigators, sponsors, and regulators in clinical trials. In practice, because drug safety is seen as a cost center and not a revenue generator, it doesn’t always get the same attention as efficacy – typically less than 0.5% of pre- and post-market budgets. This budget pressure will only continue to increase as we move into increasingly sophisticated oncology and immunology trials, which experience high volume of SAEs and potential safety signals. Complicating matters, adverse reactions in these therapeutic areas are frequently caused by the underlying disease and require more expert statistical analysis to identify valid drug-related signals.

Do sponsors have adequate resources to manage safety?

Only a handful of the largest sponsors have the resources to assemble a global safety organization. They have the in-house scientific expertise and large pharmacovigilance departments, but still struggle with compliant safety reporting. For small and emerging biopharma organizations, building safety functions entirely in-house can be prohibitively expensive.

As a result, these smaller sponsors typically turn to niche service providers to provide that expertise. Niche companies tend to respond in a narrow sense, handling just safety documentation or intake of SAEs from sites. Other models, meanwhile, provides end-to-end service, but do so by pooling offshore resources. That makes it affordable, but it doesn’t ensure proper expertise.

If you’re working on a generic that's well understood, that may be adequate. But if you have a new potential cancer treatment, it’s not.

Too often, these smaller companies feel that the only options are cost-prohibitive or of dubious quality. We recently took on a small biopharma client after it had its drug kicked back by the FDA for safety concerns; their safety information didn’t meet FDA standards and requirements. It had outsourced its safety function to a large organization where it was a small fish in a very large pond. That rarely works out well.

Why do sponsors overreport?

There are several reasons. Fear of noncompliance is one. Another is the fact that safety reporting is difficult. Complexity and ambiguity demand interpretation. It’s not easy.

A third major reason is the lack of global harmonization, which our research has identified as the single biggest headache for pharma execs. For example, the EMA’s philosophy is to send everything that the investigator has identified as a serious adverse reaction, whereas the FDA asks the sponsor to make the final determination on whether the serious adverse event was caused by the drug. This variation in local country rules provides an incentive for sponsors to overreport. It’s understandable: We’ve seen at least 40 different approaches to handling SUSAR distribution, and it changes regularly

Many sponsors lack the regulatory intelligence required to adhere to each country’s rules. So being overly cautious, they overdistribute. It goes back to that fear of noncompliance: “Better to send than not send,” is the default position. And that leads to massive overreporting.

What are the consequences of overreporting?

There are several. I’ll touch on the three primary ones:

1.Increasing the risk of missed signals: Ironically, overreporting leads to underreporting of the real safety issues. By overwhelming sites with alerts, we increase the likelihood that they will miss information that’s critical to patient safety. The FDA’s third-most-common inspection finding pertaining to clinical investigators is underreporting of adverse events.

2. Overburdened sites balk: Rather than being actionable documents, the reports end up being a time-consuming nuisance. As a result, sites are pushing back and are refusing to process events that are not identified and labeled as SUSARs. Some sites now refuse to work with certain sponsors because of the onerous safety-reporting burden. Other sites are increasing the cost to sponsors.

3. Noncompliance: Overreporting fails to give the FDA what it wants. The FDA wants a thorough analysis of the events that matter. If there isn’t a serious analysis, you’re not really protecting the trial participants or future user of the therapeutic.

What can these smaller organizations do?

They need to be proactive rather than reactive. With so many other issues to worry about, small and emerging biopharma aren’t always proactive about implementing a reliable safety solution. Then, first time they want to do a global trial, all these gaps become clear, causing them to scramble and often end up with the wrong partners.

Small and emerging biopharma companies need, from the outset, to find a flexible, scalable partner that helps them handle case processing in a regulatorily compliant manner. As we’ve discussed, case processing is often outsourced overseas. Having a dedicated US-based team you can trust is critical for quality work.

They also need access to regulatory intelligence and the ability to automate safety reporting. The regulatory intelligence tells you actionable, proven best practice interpretation of local requirements. The ability to automate allows for a streamlined approach to ensuring the right reports go to investigators and ethics committees, eliminating any over- or under- reporting of safety letters.

Any final thoughts?

Small and emerging biopharma companies should view safety as an end-to-end process that starts with protocol development and identification of potential patient populations and continues long after approval. The current piecemeal approach is onerous for sites, risky for patients and costly for sponsors.

To serve these organizations, WCG offers the industry’s only Total Safety Solution — flexible, scalable solution that provide sponsors with dedicated teams to look at each new drug safety signal, deliver high-quality case processing, and offer well-rounded expertise in all facets of PV and drug safety operations.