How much safety data should be collected in clinical trials of approved drugs?

1. How much safety data should be collected in clinical trials of approved drugs? Group 3: Jeremiah Aakre, Christopher Chow, Ryan Frank, Tanya Halvorsen, Jonathan Inselman, Heather Jerry, Jessica Kornaus, Janice Lee

2. Always Collect • Data in special populations - i.e. pediatric patients, nursing women. • Certain adverse events - SAE, death and events that lead to dose modification/discontinuation • Data for study subjects who withdraw - need to probe for reasons why, validity at stake • Targeted adverse event data - designated based on safety profile, pharmacology, or patient population...even if not serious • Long-term exposure to chronic usage treatments - characterize time course of risk

3. Why/ How Selective Safety Data Collection • Improve utility of the safety database without compromising the validity of the trial • Ease burden on investigators and participants • Lower costs • Improve use of clinical trial resources How? • identify up front what you will or will not collect • Collect certain safety data in only a random subset of the study population (omit non serious) • Less frequent collection of safety data • Mostly appropriate for trial with lengthy follow-up

4. Where to Draw the Line • Guidance for Industry article mentions briefly that collection of data that is 'no longer useful' and can even have negative consequences if it leads to: • disincentive to investigator participation in trials • increasing difficulty, time, and cost

5. Don’t Collect • Non-serious adverse events - if events are mostly understood and the drug is far along in development, additional data collection may add little or nothing at all • Routine lab monitoring – don’t draw labs simply to report data if no suspected issues. It will increase your cost exponentially. • concomitant medications with known interactions – tracking this will not help you much. • H&Ps – little use on routine basis.

6. Example: HEAAL Study • Compare the clinical outcome from two doses of losartan • Primary endpoint • Composite of death or admission for heart failure • Tracked adverse events with ARB • Hyperkalemia/Hypotension/Angioedema • Prioritize serious conditions • Most clinically relevant outcome • Mild, tolerable adverse reactions not be clinically relevant

7. Bottom Line • Certain safety data you will be mandated to collect and report • The question is what should you plan ahead of time to track – it’s a judgment call: • As an investigator, you certainly have some moral imperative to track safety data to the extent that your funding can pay for it • Easier in an investigator initiated trial rather than an industry initiated/sponsored trial • Ultimately you really should have a method to look at all ADRs and unexpected ADRs