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What Is Per-Protocol Analysis?

By Motley Fool Staff – Jul 18, 2016 at 9:02PM

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A per-protocol analysis of a clinical trial includes only patients who followed the rules to the letter, but there's a lot more investors should understand.

A per-protocol analysis is an interpretation of randomized clinical trial results that removes data from patients who didn't comply with the protocol. Imagine a trial designed to test experimental drug A against standard treatment B. If some patients drop out of the trial before investigators can measure the primary outcome, a per-protocol analysis wouldn't include their results with patients who completed treatment.

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For investors, it's important to know that the U.S. Food and Drug Administration has a long-standing concern with any removal of data, especially if its removal isn't random. In the preceding example, removing patients who dropped out of the trial is anything but random.

What to expect

If you're investing in biotech stocks that hinge on trial data, you don't want to make decisions based on per-protocol analyses alone. The FDA allows their inclusion in a new drug's application, but expect the regulator to look at all available data following patients' randomization into groups, or an intention-to-treat analysis.

As an example, Clovis Oncology investors learned this lesson the hard way in 2015. The company had presented interim data from a phase 2 trial that suggested its lung-cancer candidate, rociletinib, produced an overall response rate of 60% in patients receiving a 500 mg dose. Savvy biotech investors would have noticed that the data set included just 243 of 456 patients receiving the drug.

You want all the data?

Months later, after the FDA began its review of rociletinib's application, the agency requested additional data. Whether Clovis tried to submit a per-protocol analysis that jived with previously presented results is unclear, as well as confidential. We learned that in the intention-to-treat analysis, which includes all patients following their randomization, the 500 mg dose produced a less exciting 28% confirmed response rate.

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The market subsequently hammered the stock, which continued to slide after an independent advisory panel recommended that the FDA wait for additional data before making a decision about rociletinib. Clovis has since scuttled the rociletinib program to focus on another candidate. 

If there's one important takeaway from the rociletinib meltdown, it's this: Per-protocol analyses are useful, but don't put your money down until you've seen all the available data.

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