Change in Pill Color Plays Role in Rx Adherence
By Michael Smith, North American Correspondent, MedPage Today. Published: January 02, 2013. Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania
Something as small as the color of a generic medication can confuse patients enough to interrupt their treatment, researchers reported.
In a case-control study, changes in pill color increased the risk that patients would not refill their anti-epileptic drug prescriptions, according to Aaron Kesselheim, MD, JD, of Brigham and Women's Hospital in Boston, and colleagues.
There was no statistically significant effect on refill rates based upon changes in pill shape, Kesselheim and colleagues reported online inArchives of Internal Medicine.
The researchers noted that generic medicines account for over 70% of U.S. prescriptions, and the proportion is expected to increase as some widely used drugs come off patent.
Such generic drugs must be biologically equivalent to the approved brand-name product, but they often vary in size, shape, and color, they noted.
"A patient taking five medicines, each produced by five generic manufacturers, theoretically faces over 3,000 possible arrays of pill appearances for what are, chemically and clinically speaking, the same drugs," Kesselheim and colleagues noted.
Those choices could confuse patients and result in poor adherence to therapy, they noted.
To investigate the issue, they conducted a case-control study among commercially insured patients who were taking an anti-epileptic medication. Cases included 11,472 patients who failed to refill a prescription within 5 days of the time they ran out of pills; the controls, 50,050 patients, had no refill delays and were matched to cases by sex, age, number of refills, and the presence of a seizure disorder diagnosis.
The researchers looked at the two refills preceding the failure to renew and determined whether or not the pill color and/or shape matched.
- The drugs dispensed had 37 colors and four shapes.
- A color mismatch discordance preceded 136 cases (or 1.2%) but only 480 controls (or 0.97%). Those numbers yielded an adjusted odds ratio of 1.27 (95% CI 1.04 to 1.55).
- A shape mismatch preceded 18 cases (or 0.16%) and 54 controls (or 0.11%), for an odds ratio of 1.47 (95% CI 0.85 to 2.54).
- Within the seizure disorder diagnosis subgroup, the risk of failing to renew after a color change was also elevated, with an odds ratio of 1.53 (95% CI 1.07 to 2.18).
The researchers cautioned that the absolute magnitude of the effect was small, so "changing appearance may have a small overall effect on medication adherence."
In addition, they noted, the focus on anti-epileptic drugs limits generalizability of these results, since patients and their physicians "may be particularly attentive to their pills' appearances."
As the use of generic drugs increases, the issues raised by the study "will become ever more urgent," commented Lawrence Yu, PhD and Gregory Geba, MD, both of the FDA's Office of Generic Drugs in Rockville, Md.
In an accompanying commenter articles, they noted that the FDA "is not charged to regulate products with regard for aesthetic factors such as pill color or shape."
But they added, agency reviews have begun to look at visual aspects of products "that could have an impact on patient compliance."
It will be interesting, they wrote, to see if studies of other types of drugs yield similar findings.
Journal associate editor Kenneth Covinsky, MD, commented that editors were initially divided on the significance of the finding. Some thought the effect was small, while others noted it could add up over time, he wrote in an editor's note.
But in the end, Covinsky wrote, the editors agreed that generic medicines should be required to look like their brand-name counterparts.
"Subjecting patients to this risk is absolutely senseless and absurd," he wrote. "With all the hurdles patients face, how on earth can we justify confusing them by needlessly changing the appearance of their medicines?"
The study had support from the Agency for Healthcare Research and Quality and the Robert Wood Johnson Foundation Investigator Award in Health Policy Research.
Kesselheim did not report any financial links with industry. Co-authors reported links with CVS Caremark, Aetna, the Commonwealth Fund, the Robert Wood Johnson Foundation, Teva, Lilly, and the National Association of Chain Drug Stores.
The journal said the comment authors did not report any potential conflicts.
Covinsky is associate editor of the journal.
Primary source: Archives of Internal Medicine
Kesselheim AS, et al "Variations in pill appearance of antiepileptic drugs and the risk of nonadherence" Arch Intern Med 2012; DOI:10.1001/2013.jamainternmed.997.
Additional source: Archives of Internal Medicine
Yu LX, Geba GP "Generic pills from the patient perspective: Dressed for success?" Arch Intern Med 2012; DOI: 10.1001/jamainternmed.2013.2283.
Additional source: Archives of Internal Medicine
Covinsky KE "Debating effect sizes" Arch Intern Med 2012; DOI: 10.1001/jamainternmed.2013.1545.