Hetero sapiens: The Crack in the Crystal Ball

What happens when you compare clinical trial results in different populations?

Anthony Almada, B.Sc., M. Sc.

Inset: Would a nutraceutical product subjected to a clinical trial among a cohort of one geographic population show similar effects in a cohort from a remote, different population?
Setting: The Metabodome (a biological laboratory in an enclosed stadium), San Diego, CA
Date: March 2012

“Good afternoon ladies and gentlemen and welcome to the World Series of Biology—the WSB. I’m Rich Powell and I’m joined by Dr. Sheila Jacks, 4-time All-Pro metabolism and pharmacology scientist, and our clean room commentator, Dr. Erika Erickson, the 2010 winner of the Nobel Prize in Physiology or Medicine for her contributions to human metabonomics, which studies the comprehensive, dynamic metabolic response to biological stimuli or genetic manipulation.

“For those of you who are first time viewers, the WSB pits the top 12 executives from food, beverage, drug and dietary supplement companies a­gainst each other. Their aim: to determine which ethnic group will re­spond favorably—‘Responders’—to each of nine different interventions—new agents or combinations of currently used agents, synthetic or natural. Sealed off in five different mini biodomes are 36 individuals—and 6 alternates—each from the same ethnic group and the same small, geographically defined region, with similar ages. The countries represented in the 2012 WSB include: Australia, China, India, Germany and the U.S. In today’s round here at the impressive Metabodome the test agent is a beverage. It’s biotime, so down to you, Erika!”

“Thank you Sheila and Rich. You can feel the excitement here in the air, as clean and particulate-free as it is. The test beverage—CP219—is in­tended to reduce inflammation and joint pain. Each of the subjects in the mini biodomes—their home for the past three months—has been dosing with CP219 for eight weeks. Urine and blood metabotyping, along with bio­scans of all of the joints, have been performed in the subjects—before dosing began, at four weeks after dosing, and this morning. The metabonomic and bioscan results have been tallied, with the Responder results sealed by the CEO of a top two accounting firm. Each of the execs has access to video and audio feeds from each of the mini bio­domes—the same those of you at home with octaplex Peak Definition monitors are enjoying. The execs have five minutes to discern if one group, as a whole, seems to be more of a ‘Responder’ than the other group. The twist: bluffing and acting by any of the subjects in any of the domes. Within each biodome cohort are five skilled actors, unbeknownst to each other, any of their dome mates or the execs. The Thespian Placebo effect! Back to you upstairs.”

“Thank you Erika! Sheila, one has to wonder if the past two years of WSB have left their mark on the execs…”

“Rich, you are so right to ask that. Two years ago we saw the drug execs break from the pack and start selecting Responder countries through pharmacogenomic and statistical analyses of data from other agents. This approach proved to be spot on, with back-to-back co-victories for two pharma execs, who have since hung up their lab coats and retired from WSB competition. This really shook up the food/beverage/dietary supplement execs—the FBDs—who had made the costly assumption that what works in India works in Indiana and Iberia. This had a ripple effect upon these three industries, which had made the unfounded, myopic assumption that cheaper clinical trials in India and China—with positive outcomes—would translate to populations of Europeans and North Americans. And then the flurry of consumer class action suits against…oh…Erika, back to you!”

“Thank you Sheila! It is crazy down here in the domes. All of the execs have submitted their votes. And the teams from India and Germany are ecstatic—as if they know something we don’t. Here are the Responder results: Australia—NO; China—NO, with adverse events; India—YES, and with weight gain; Germany—NO, and with increased upper respiratory tract infections; and the U.S.—NO, and with elevated LDL cholesterol. What a shock!! We have NEVER seen weight gain manifest in any past WSBs with any agents not intended to modify body weight or body composition. Sheila and Rich—what’s it like up there in the execs booth?”

“Well Erika, it’s a three-peat for the pharma execs this year. The three pharma players correctly predicted the Responders in India, with the FBDs left aghast and agape. Wait—one of the execs, yes, a dietary supplement exec, is protesting, claiming that weight gain in the India biodome cohort nullifies the Responder outcome. But this exec voted that all five of the biodome cohorts would respond. It’s up to the head referee. No—he waves the black DNA double helix flag. Protest denied. The pharma execs win an unprecedented three times. What will it take for the FBDs to change their strategy? We’ll have to wait for the next round of the World Series of Biology.”NW