When a drug is developed, the expectation is that a person with cystic fibrosis (CF) will adhere fully to the prescribed regimen. Unfortunately, in the real world this expectation is unrealistic given the complexity and time burden of the typical CF regimen. Adherence to chronic pulmonary medication ranges between 35-75% depending on the drug and person’s age.^1,2 People with CF, their families, and even their care teams often wonder how much adherence is enough and if what they are doing is making a difference. The study by Eakin and colleagues¹ reviewed in this issue demonstrated that higher adherence is associated with better health outcomes — specifically less need for IV antibiotics for pulmonary exacerbations. This first-of-its-kind paper will have to be replicated with larger samples to better understand the impact of adherence to each drug and among subgroups. For example: does the strength of the association between adherence and health outcomes vary by disease severity, age, gender, and other factors? Regardless of its limitations, this study has confirmed that medication adherence matters.

Logically, then, it seems imperative that adherence be assessed at each clinic visit to both inform treatment decisions and to provide adherence-promoting interventions. In other illnesses, it is known that patient-reported adherence is consistently higher compared to objectively measured adherence (eg, pharmacy records or electronic monitoring) and that physician judgments of adherence may be biased.^3,4 The work by Daniels and colleagues,⁴ discussed in this issue, showed that when reporting on nebulized medication use, these biases are found among people with CF and the various members of the care team. Therefore, having an objective measure of adherence available would be ideal.

Pharmacy refill records offer an objective estimate using existing data that is increasingly becoming available without charge to physicians through e-prescribing and electronic health records. The limitation, however, is that refill records require at least a year of data to get a stable estimate; and a substantial and sustained behavior change to produce changes in refill-based adherence scores. In contrast, electronic monitoring of adherence, such as the I-Neb used by Daniels et al, provides a date/time stamp that reveals patterns of use and short-term increases or decreases in adherence, which is helpful in identifying barriers and facilitators of adherence. Unfortunately, electronic monitors can be costly, require additional staffing to manage, and are not yet widely approved for use as a drug delivery device. Regardless, electronic devices should continue to be developed and tested, as they provide the most comprehensive adherence information possible.

After identifying that a patient is not optimally adhering to therapy, the next essential step is to understand the specific barriers the patient encountered so that effective counseling and support may be provided. George et al⁵ and Bregnballe et al⁶ both evaluated potential adherence barriers and facilitators of adherence among adolescents and young adults with CF using qualitative interviews and a web-based survey (respectively). What is clear from their results is that people face a wide variety of challenges and more often than not several barriers at a time. These barriers range from easy fixes that require a one-time intervention to more complicated psychosocial challenges that will require ongoing support and possible referral to behavioral health counseling.

The most challenging aspect of adherence is finding the right intervention for each specific individual. Systematic reviews have concluded that across the spectrum of illnesses and behaviors (medication, diet, etc), education-only interventions are less effective than multicomponent interventions in improving adherence and illness self-management.^7,8 Multicomponent interventions almost always include education, but also provide one or more additional components: behavior modification, parent training, problem-solving, motivational enhancement, behavioral and health feedback, and social support.

A recent Cochrane review of self-management education interventions for CF by Savage et al,⁹ reviewed in this issue, concluded that despite methodological limitations of the studies, there was evidence that the interventions increased patient knowledge immediately after intervention delivery. Unfortunately, changes in knowledge did not effectively translate into sustained behavior change or improve health outcomes. Thus, much like other illnesses, interventions to support adherence in CF will probably have to reduce their focus on education and become increasingly multicomponent.

Exciting opportunities for new interventions lie in the use of technology, particularly cell phones and smartphones. There is great interest in developing mobile health (mHealth) applications such as social networking and gaming, and evaluating whether these high-use technologies can be used to support adherence. As discussed in this issue, the report by Marciel and colleagues¹⁰ provides preliminary evidence that their CFFONE^™ program is of high interest to people with CF and is perceived by patients, families, care teams, and technology experts as potentially likely to improve adherence. A randomized trial is currently under way.

In just the past few years, the field of CF adherence research has progressed dramatically. There is greater understanding about the importance of adherence, how to measure it, and which interventions might be effective. With several adherence trials in progress, our knowledge and our ability to help people with CF balance the need to follow their complex regimens while continuing to have a “normal” life is likely to increase in the coming years.

Commentary References

1.	Eakin MN, Bilderback A, Boyle MP, Mogayzel PJ, Riekert KA. Longitudinal association between medication adherence and lung function among people with cystic fibrosis. J Cyst Fibros. 2011;10: 258–264.
2.	Daniels T, Goodacre L, Sutton C, Pollard K, Conway S, Peckham D. Accurate assessment of adherence: self-report and clinician report vs electronic monitoring of nebulizers. CHEST. 2011;425-432.
3.	Stone AA, Turkkan JS, Bachrach CA, Jobe JB, Kurtzman HS, Cain VS (Eds). The Science of Self-Report: Implications for Research and Practice. Mahwah NJ:Lawrence Erlbaum Associates Inc. 2000.
4.	Miller LG, Liu H, Hays RD, et al. How well do clinicians estimate patients' adherence to combination antiretroviral therapy? J Gen Intern Med. 2002;Jan;17(1):1-11.
5.	George M, Rand-Giovannetti D, Eakin MN, et al. Perceptions of barriers and facilitators: self-management decisions by older adolescents and adults with CF. J Cyst Fibros. 2010;9:425-432.
6.	Bregnballe V, Schiotz PO, Boisen KA, et al. Barriers to adherence in adolescents and young adults with cystic fibrosis: a questionnaire study in young patients and their parents. Patient Prefer Adherence. 2011;507-515.
7.	Haynes RB, Ackloo E, Sahota N, et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008;Apr 16;(2).
8.	Kahana SY, Drotar D, Frazier T. Meta-analysis of psychological interventions to promote adherence to treatment in pediatric chronic health conditions. J Pediatr Psychol. 2008;Jul;33(6):590-611.
9.	Savage E, Beirne PV, Ni Chroinin M, et al. Self-management education for cystic fibrosis. Cochrane Database of Syst Rev. 2011, Issue 7. Art. No.: CD007641. DOI: 10.1002/14651858.CD007641.pub2
10.	Marciel KK, Saiman L, Quittell LM, Dawkins K, Quittner AQ. Cell phone intervention to improve adherence: cystic fibrosis care team, patient, and parent perspectives. Pediatr Pulmonol. 2010;157-164.