Why Similar Studies Get Different Results


I my last post, I recounted how I was able, finally, to discover the location of the studies that Robert Staples, head of toxicology for DuPont, had conducted in 1980 and 1982, that we needed to help document our case. They had been cleverly hidden under special luncheon memos where no one else was likely to search.

 

While the results of the Staples studies weren’t quite as bad as those of the University of California study, they certainly weren’t good. It appeared that Staples had tested the product in two different studies and got two different results.

 

DuPont had been trying to get its product licensed since 1977. At the time it conducted the 1980 study DuPont had a Rebuttable Presumption Against Registration (RPAR) that it had to use to warn pregnant women about possible birth defects caused by exposure to Benlate. To lift the this RPAR, DuPont needed to prove that its product was safe. The 1980 Staples study did not accomplish that. So DuPont went back and repeated the study in 1982, but this time the results were much better. Purportedly it was the same study, but all of a sudden the results were much better, because they weren’t finding as many malformations this time around.

 

We were baffled by the differing results.

 

Armed with the 80,000 pages of documentation from DuPont, I was able to take Staples’s deposition. In preparing for that deposition, I smelled a rat—and it wasn’t a lab rat. There had to be something different in those studies. I wracked my brain, reading and rereading the studies and the underlying data until it finally came to me.

 

One study was histological, and the other was clinical.

 

A histological study is better, because it’s carried out with a microscope, and the measurement (in this case, of the eyes) is actually calculated mathematically. If the eyes were undersized, they were called microphthalmic, which means there was a negative effect—the eyes didn’t grow enough and it was considered a malformation.

 

In contrast, clinical studies are based largely on opinion: some guy in a lab says, “Looks good to me.” He is essentially eyeballing the results and then moving on to the next rat. You can easily get better results from a test like that than you can when you are conducting a mathematically based histological study.

 

Finally, when scientists conduct these studies, they compare milligrams of the chemical to kilograms of body weight (mg/kg).

 

In a well-designed study, the rats will be weighed every day. Rats aren’t like humans; they grow really fast, which means their weight can change very quickly. This can radically affect the ratio of milligrams to kilograms.

 

In the more scientific 1980 Staples study, the rats were weighed daily, which provided a true and accurate comparison of dose-to-weight measurement.

 

In 1982, however, the rats were not weighed daily, and therefore the information in this second study produced artificially better results for DuPont and could not be considered anywhere near as accurate as the 1980 study.

 

Staples admitted the methodology was good for the 1980 study but couldn’t explain why the results were so bad. His only attempted explanation for the improved results in 1982 was the availability of better “computer technology.” When we pressed Staples in his deposition, however, he admitted that the two studies had different methodologies and that the preliminary report he prepared in 1980 wasn’t so good for DuPont. The results showed signs of eye malformations at very low testing levels.

 

As it turned out, Staples caught a lot of heat from his superiors—even though he was the head of toxicology—for preparing the report without prior review from the higher-ups in the company.

 

My colleague Marjorie and I felt we had struck gold when we found those rat studies—especially the Staples studies. Now, after the depositions, it was clear that in fact we had.

 

“You’re the best, Jim,” she said.

 

I heard this from her often, which felt good.

 

Really good.

 

In my next post, I divert from the case at hand to speak a little about my colleague Marjorie.

 

You can find a lot more about my background in my book, Blindsided, from which this blog post is adapted.

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