Originally Published PMPN September 2001
The Blistering Issue of Patient Compliance
The future of compliance packaging holds many exciting possibilities.
Erik Swain, Senior Editor
In recent years, both the healthcare industry and the general public have become more aware of the fact that poor patient compliance leads to failed medication regimens. There also seems to be an increased awareness of how labeling and packaging, especially unit-of-use packaging such as blister cards, can help patients with compliance.
"As a practicing pharmacist, I witness better compliance with blisters, such as those used for hormonal-replacement therapy, than with medication in vials for the same therapy," says Joseph Urban, RPh, MBA, senior director of ProClinical Inc. (Phoenixville, PA). "Blisters promote compliance more so than bottles. They present a means by which a patient or subject will know what dose was taken last or what dose was missed."
But these lessons are not always being applied by the drug companies during the package development process, some blister manufacturers say. While in some cases the drug manufacturer places a high priority on designing packaging to enhance compliance, attention given to compliance issues varies greatly from firm to firm and from product to product.
"Not all companies understand the urgency of having a package that promotes compliance of their product," says Howard Thau, president of Sonic Packaging Industries Inc. (Westwood, NJ). "The customer, the product, and how the product is being distributed all come into play. For example, in cases where the product needs to be taken at a specified time to get the full benefit of the medication, the manufacturer is more likely to be attentive to compliance issues."
There is some evidence that unit-of-use packaging with compliance-enhancing features does cause patients to follow their regimens better. And more of such evidence is being gathered. The next question is whether the knowledge gathered will be applied on a more widespread scale.
THE EVIDENCE
Securing funding for a unit-of-use packaging compliance study is not easy, industry observers say, because the matter seems intuitive, and it may not seem worth the time, effort, and money to study something that seems so obvious. However, if more industry professionals familiarize themselves with existing and planned compliance studies, the industry will reap the benefits of improved package development, better patient compliance, better health outcomes, and lower costs from fewer medication failures.
The Agency for Healthcare Research and Quality, which is part of the U.S. Department of Health and Human Services, issued a report in July 2001 called Making Health Care Safer: A Critical Analysis of Patient Safety Practices. Chapter 10 of that report, "Unit-Dose Drug Distribution Systems," analyzes studies of unit-dose dispensing systems in hospitals and concludes that "overall, unit-dose [dispensing systems] appear to have little potential for harm. The results of most...observational studies seem to indicate that it is safer than other forms of institutional dispensing. However, the definitive study to determine the extent of harm has not yet been conducted."
The studies surveyed, conducted between 1970 and 1998, are "overall relatively consistent in showing a positive impact on error reduction" despite "important methodologic problems," the agency stated in the chapter, which can be viewed at http://www.ahcpr.gov/clinic/ptsafety/chap10.htm.
An important facet of this document, says Robert Case, president of Reed-Lane Inc. (Wayne, NJ), is that it reports that 92% of acute-care hospitals are now using unit-dose dispensing, and 80% of hospital pharmacy directors surveyed reported that they use unit-dose dispensing for at least 75% of oral doses.
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| Blister packaging with calendar-like features can enhance compliance. |
A study by Gail Ware et al. published by the New Zealand Medical Journal in 1991 found that elderly patients using unit-dose calendar packaging were more likely to comply with their regimens than those using bottles or other noncalendar packs. The calendar-pack users led in compliance rates by 86.7 to 66.7% at the start, 68.8 to 41.0% after 10 days, 64.4 to 38.5% after one month, and 48.9 to 23.1% after three months.
Another study, conducted by Walter Leonard, MD, and Dawn Leonard, RN, BSN, published in the September 1984 issue of Maturitas, the international journal for the study of the climacteric, found that a "calendar-oriented, structured dosage package" increased patient compliance with estrogen-replacement therapy as compared with a two-drug regimen administered from bottles. Over the life of the study, 82% of patients complied with the calendar pack as opposed to 30% who complied with the bottle regimen.
Soon there may be more studies added to the body of evidence. Ohio State University is applying to the Healthcare Financing Administration for funding of a study to compare compliance rates of an anti-hypertensive drug administered to some elderly patients in a bottle and others in a blister. A funding decision had not been made at press time.
"We are interested in studying the impact of packaging on elderly patients with chronic diseases, particularly considering that there could be a prescription drug benefit added to Medicare," says Philip Schneider, a clinical professor at Ohio State who would lead the study. "We want to look at whether a packaging system could promote not only pharmacotherapy, but safety."
Also in the near future, the results of a study at the University of Florida's College of Pharmacy could emerge. While not focusing directly on compliance, it is examining some related areas, including how much time unit-of-use packaging saves in the pharmacy, to what extent unit-of-use packaging prevents errors, and how well consumers accept the idea of unit-of-use packaging, says David Brushwood, the professor in charge of the project.
There is significant anecdotal evidence as well for the blister's superiority in promoting compliance. For example, says Thomas Intini, president of Intini Marketing Inc. (Brossard, QC, Canada), the people in every focus group he has conducted have come to the conclusion that "compliance packaging in a blister format is far superior than bottles."
The Healthcare Compliance Packaging Council (HCPC; Falls Church, VA) has a bibliography of materials on unit-dose packaging and compliance on its Web site at http://www.unitdose.org/bibliography.htm.
COMPLIANCE AND BLISTER DEVELOPMENT
The information on HCPC's Web site is making its presence felt in the package development process, but there is still a long way to go. "If the cost of the package is not critical, the newer formats of a blister within a die-cut board are compliant, child resistant, and senior friendly," says Bill Schmitt, market development engineer for Pharma Center Shelbyville (Shelbyville, KY), an Alcan Packaging company. "Products that are not highly toxic to children are able to be packaged in a child-resistant, senior-friendly blister. But drugs requiring a very low-access blister are difficult to make senior friendly."
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| Manufacturers are using blisters to encourage compliance, but approaches vary. |
Judi Crowe, director of marketing communications for PCI Services (Philadelphia) says that manufacturers "should think of compliance features as value-added services that they are giving to the patient. If patients are compliant, they will use more product, which makes it more cost-effective for the manufacturer."
Suppliers say they have noticed more of an interest in the issue on the part of their pharmaceutical clients, but sometimes issues such as cost and regulatory requirements take precedence. "More and more, we work closely as early as the stability test to help them take advantage of our knowledge" on how to develop a compliance package, says Luc Vaugeois, MBA, director of sales and marketing for Ropack Inc. (Montreal). "Compliance issues are usually very important to them, but there is a difference between pharma, big pharma, generics, nutritionals, and biotech companies, and all together there are differences in each corporation."
"Sometimes companies will state exactly what they want, and we will build a package around that. Other companies will present their product and ask us to design the whole concept," notes Intini, whose firm's products include a device enabling seniors to push pills out of blisters and a unitized heat-seal compact that purports to organize pills like a blister but provide better shelf life. "In that case we will come up with compliance packages for over-the-counter, prescription, physician samples, even variations for focus-group study. But it is important to get as much input from the pharmaceutical firm as possible, although some of them don't think of packaging until the end, when it should be thought of at the beginning."
In some cases, perceived deficiencies with bottles have led drug companies to question their suppliers on other forms of packaging that could produce better patient compliance. "On bottles with outserts, some of our clients were not sure that their customers were actually reading the instructions," says Marjanne Troost Meyer, director of contract packaging for Margo (Montreal, QC, Canada), an Alcan Packaging company. "But if they use a fold-over card with a blister, it is easier for them to get their message across to the end-user. In that format, they can insert booklets, leaflets, coupons, or other components that provide more information. They do need, however, to understand that the blister-packaging process may take longer when a card is involved."
Clinical-trial packing tends to be at the forefront of compliance packaging design because the results of a clinical trial are highly dependent on subject compliance. "Certain types of blinded clinical trials, such as those using a double-dummy format or overencapsulated products, may have additional compliance issues such as the number of doses to be taken at a given time or the size of the dosage unit," notes Urban. "These issues may have a negative impact on compliance."
Another reason for the increased interest in designing compliance packages is the transition of some drugs from multidoses per day to one dose per day or even one dose per week, says Ed Hancock, president of American Health Packaging (Columbus, OH), the packaging unit of AmeriSource. "With those drugs, if you miss a dose, there is a greater effect," he says. "Therefore, compliance becomes more critical."
COMPLIANCE FEATURES
Perhaps the most significant advantage that blisters, especially carded blisters, have in promoting compliance is that they have a lot of easy-to-see space for instructions on how and when to take medication. "What really makes a difference is the ability to print clear instructions for the dosage regimen, whether you're printing the days and the weeks on the package or providing a day label," Crowe says. "Graphics that reinforce those instructions are very important as well."
"One of the best compliance features would be a chart or device that indicates the dosage used and when the dosage was taken," adds Michael Castaldo, director of package development at Reed-Lane. "This feature usually has good results and is merely a printing and formatting solution as opposed to a design issue. The use of heat-seal cards enhances the ability to provide this feature and allows a larger billboard for displaying time and sequence instructions. The card also allows the patients to make notes."
In addition, he says, "bar codes are becoming essential in packaging operations that require multiple strengths of a product to be packaged into a single unit. The bar codes provide a means to detect and verify that the correct strengths are placed in the proper locations."
CHILD RESISTANCE AND COMPLIANCE
Suppliers note, however, that at times child-resistant (CR) features are a stumbling block to the use of compliance features. Not only can it be complicated and expensive to make a blister child resistant, senior friendly (SF), and compliance enhancing all at once, but sometimes a firm perceives that CR–SF requirements and compliance requirements are contradictory and chooses to concentrate only on meeting CR–SF mandates.
"In the United States, developing compliance packaging is tricky because of the CR–SF regulations," says Angela Roggenhofer, healthcare marketing manager for the Americas at Hueck Foils LLC (Wall, NJ). "I wonder why there are not more products in calendar packaging, on which the printing can help a lot."
Thau agrees. "Ideally, you can have child resistance and compliance, though having these and making it senior friendly is a challenge," he says. "It can be done if you add secondary packaging such as cards."
But more solutions are emerging every day. When the Dosepak, a carded blister from Mebane Packaging Group, a Westvaco Packaging Resource (Mebane, NC), won HCPC's Compliance Package of the Year award recently, judges cited its combination of CR–SF and compliance-enhancing features as a major reason for the honor and noted the similar potential of many of the other entries.
CONCLUSION
As the case for compliance packaging, often in the form of blisters, becomes more and more evident, drug companies will demand it more. Some may even follow the lead of generic-drug manufacturer Able Laboratories Inc. (South Plainfield, NJ) and focus on compliance packaging when marketing a new drug treatment.
Able's product combines an antibiotic to treat a urinary tract infection and a urinary analgesic to relieve the symptoms of the infection into a single blister package. Not only does the company expect the package to enhance compliance, it expects it to reduce total costs because the patient only needs to fill one prescription instead of two. The patient is also less likely to be admitted to the hospital if he or she takes the medication properly, and ultimately, the pharmacist spends less time dispensing the medication.
No matter what path it may take, "There is an exciting future ahead for compliance packaging," says Castaldo. "I see many more applications for this type of packaging surface every year. Multidosage forms inside the same packaging are becoming more popular. There is a large need for this in hospital pharmacies and nursing homes, where dispensing of multiple medications is commonplace. Compliance packaging would enhance methods for applications requiring patients to take multiple medications at various intervals."
Copyright ©2001 Pharmaceutical & Medical Packaging News
Photo courtesy of Margo, an Alcan Packaging Co. Photo by Claud-Simon Langlois.
