Designing a trial for the treatment of cancer is hard. Designing a trial to prevent cancer is even harder. In a typical population, such a small percentage of people will naturally contract a particular type of cancer that to test the ability of an intervention to reduce that number may require tens of thousands of subjects to be followed for decades. That’s not a cheap, or easy, study to run.
But in a population where the risk for a particular cancer is elevated, a prevention study might be both possible and immediately helpful. One such situation is found in the unfortunate case of Bangladesh, where charity efforts in the 1970’s to provide pathogen-free sources of drinking water accidentally exposed 40-70 million people to water tainted with arsenic. The disease epidemiology of that long-term exposure was recently characterized by Habibul Ahsan, director of the Center for Cancer Epidemiology and Prevention at the University of Chicago Medical Center, whose HEALS study found increased mortality and cancer in a study of more than 20,000 people.
In addition to characterizing what has been called “the largest mass poisoning of a population in history,” Ahsan has also been leading a study to try and offset some of its damage. The Bangladesh Vitamin E and Selenium Trial, or BEST, is testing two inexpensive nutritional supplements for their ability to prevent the non-melanoma skin cancer (NMSC) that commonly develops in people exposed to high levels of arsenic. The study, which recently received a $10 million renewal from the National Institutes of Health, has a twofold purpose, Ahsan explained.
“In the short term as well as unfortunately the long term, these people will be at an increased risk for arsenic-related cancers,” Ahsan said. “What we can do on the biomedical side, beyond solving the arsenic-contaminated water problem, is to identify low-cost, pharmacological or dietary/nutritional interventions. Something we can provide to these people that is feasible for millions of people at risk to take and reduce their future risk of these cancers.”
Like Ahsan’s HEALS project, the BEST study is massive in scope. In the first five years of the trial, roughly 7,000 Bangladeshi subjects were recruited and sorted into one of four groups, each required to take one pill a day for 6 years. Depending on the group, each subject will take a daily dose of vitamin E, selenium, vitamin E and selenium, or a control pill, with researchers tracking the amount of skin cancer, mortality, and other adverse events that develop by the end of the study.
Even at that size, the trial is smaller than it would be in a less vulnerable population. Because of the increased risk for NMSC among Bangladeshis exposed for decades to arsenic, a chemoprevention trial can operate with fewer subjects, Ahsan said. The infrastructure built by Ahsan’s team in Bangladesh (with collaborators at Columbia, Dartmouth, and the University of North Carolina) also saves money and ensures high compliance rates. More than 300 staff members have been hired to visit each subject on a daily basis to make sure they take their pill and to observe any side effects or illnesses.
“That’s something that’s impossible to do here,” Ahsan said. “It’s an expensive trial, but it’s a fraction of the cost had we conducted this trial here in the United States.”
With the recruitment and infrastructure settled in the first five years, Ahsan and his team were able to add some new features for the study’s next phase. After two recent trials found effects of selenium supplements on diabetes, the disease was added to the study as an outcome alongside skin cancer. Blood, urine, and tumor samples are also being analyzed in Bangladesh and at the University of Chicago for biomarkers that can help physicians determine who might need preventive treatment the most, and who might respond best to the supplements.
At a cost of just pennies per pill, any dent vitamin E and/or selenium can put in the cancer risk of the Bangladesh population could have a massive long-term health impact. Learning about skin cancer prevention in such an unusual population could also be applied in the United States, where an estimated 15 million people are exposed to unsafe levels of arsenic in their water supply and where rates of non-melanoma skin cancer are on the rise. With such far-reaching applications, the prevention trial in Bangladesh may be a fine example of making the best of a bad situation.
“The idea is we will immediately try to find a solution here, and then come up with a good answer to a scientific question that is applicable to people who are at risk of this and other cancers everywhere else in the world,” Ahsan said.