Mullins Leads $1.5 Million Study to ‘Nudge’ Better Drug Approval Trials

School of Pharmacy grant is among only six selected by NIH to improve comparative effectiveness research methods.

By Steve Berberich
December 16, 2010

A national surge in patient advocacy for more informed medical decision-making is compelling pharmacy and medical researchers to scrutinize conventional methods used in clinical trials for medications, says C. Daniel Mullins, PhD, a professor of pharmaceutical health services research (PHSR) at the University of Maryland School of Pharmacy.

“Patient advocacy groups have become much more sophisticated. In order for research to be effective we need to design clinical trials to answer questions that are important to patients and their physicians,” says Mullins.

Mullins was awarded one of only six grants recently funded by the National Institutes of Health (NIH] to investigate the best ways to conduct comparative effectiveness research [CER]. The NIH awarded Mullins and his colleagues a $1.5 million RC4 methods grant under the agency’s “Recovery Act Limited Competition: Methodology Development in Comparative Effectiveness Research.” Elijah Saunders, MD, professor and head of the division of hypertension at the University of Maryland School of Medicine, is also a key investigator on the new grant.

According to the NIH website, CER is “the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat, and monitor health conditions in ‘real-world’ settings.”

Mullins says there should be more trials that also compare effectiveness of drug candidates with on-the-market drugs for treating the same medical condition, as opposed to trials that only test the new drug compared to a placebo. He wants to improve the efficiency of conducting clinical trials, including adapting the trials based upon pre-specified adaptation rules.

Mullins also advocates the collection of more data on diverse patients, and systematically collecting and analyzing potential differences in treatment effects across ethnic, cultural, gender, racial, and geographic subgroups.

The NIH says that “the purpose of [CER] research is to improve health outcomes by developing and disseminating evidence-based information to patients, clinicians, and other decision-makers, responding to their expressed needs, about which interventions are most effective for which patients under specific circumstances.”

Comparative effectiveness should produce outcomes that are more meaningful to patients, says Mullins. “If you say this new drug lowers your bad cholesterol and maybe it doesn’t heighten your good cholesterol that is not as informative as if you can say that this new drug will lower your risk for stroke more than an alternative treatment. So part of comparative effectiveness research involves talking with patients so that we can learn what is important to the patient. We are interested in finding out what is most important to patients and then collecting those outcomes efficiently,” he says.

To conduct its research, Mullins’ team will use CER to revisit a classic clinical trial called the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT], which was a large study that began in 1994 and lasted eight years. ALLHAT compared four antihypertensive drug classes including diuretics. With the new grant, Mullins and the research team will work with the United BioSource Corporation and Berry consultants to find out if novel statistical methods could have allowed the trial to be completed with less time and expense.

“We are using the data from that trial and asking if you had designed this trial in a way that we think is more efficient, could we have learned the results faster,” Mullins explains. “We are particularly grateful to the principal investigator of ALLHAT for agreeing to work with us on this study.”

Overall, the popularizing of CER is intended to help patients, prescribers, and other medical decision-makers select the most appropriate treatments. Traditional clinical trials have strong internal validity, but may not be ideal for decision-makers considering alternative treatments that were not “standard of care” when the clinical trial was designed.

“We propose an innovative approach to designing and conducting randomized clinical trials,” says Mullins.