Monday, December 23, 2013

A Critique On The Lack Of Effective Antibiotic Adherence Interventions: How We Can Do So Much Better – Katelin Blackburn

     A world where antibiotics are no longer effective is looming a bit closer than many of us would like to admit. According to the CDC’s report titled Antibiotic Resistance Threats in the United States, 2013, at least 2 million people each year in the United States alone develop a serious antibiotic-resistant infection, and of those 2 million, 23,000 die “as a direct result of these antibiotic-resistant infections” (1). Antibiotic-resistant bacteria is a world-wide Public Health problem, and one that has been caused by many factors, including unnecessary antibiotic prescribing by physicians, the use of antibiotics in animal feed, and inappropriate antibiotic usage by patients (1). The CDC calls for “Four Core Actions to Prevent Antibiotic Resistance,” two of which directly address the need for antibiotics to be used only as directed (1). The recommendations that follow focus mainly on tracking antibiotic prescription by physicians and improving physician prescribing patterns to be more conscientious of their duty to only prescribe antibiotics when they are actually needed. Unfortunately the recommendations largely neglect how to improve the next step following physician prescription of antibiotics: the need for improved antibiotic regimen adherence for those that are legitimately prescribed the drugs. Through the implementation of an effective initiative to aid patients in fully adhering to their prescribed short-term antibiotic regimens, health practitioners can take an important step in managing the emergence of antibiotic-resistant bacteria, as well as aid their patients in decreasing their morbidities.
     Non-adherence to short-term antibiotic therapy is surprisingly common among patients. Studies have shown a variety of disturbingly low adherence rates, from one study showing 56% adherence for nine days of treatment, to another study showing overall compliance rates, measured via a biomarker added to the antibiotics, to be as low as 16% (11,17, 2). Non-adherence refers to patients taking their antibiotics in any other way than the prescribed regimen, including both unintentional missed doses as well as intentional straying from the prescribed dosage regimen. It has been shown that physicians cannot accurately predict compliance among their patients, and that compliance is not related to income, social class, occupation, or educational background (3-4).
     Non-adherence to the physician prescribed antibiotic regimen has many indirect costs (5-6). It is estimated by the National Pharmaceutical Council that as of 2005, “$8.5 billion is unnecessarily spent annually on hospitalizations and physicians visits caused by noncompliance to prescription regimens,” with 2013 estimates of non-adherence costs burdening the healthcare system with a whopping $290 billion annual cost, of which antibiotic non-adherence adverse events played an important role (18, 23). Patients’ health may deteriorate as their illness fails to cease, they may need to be admitted to the hospital, and they are contributing to the emergence of antibiotic-resistant bacteria (6). Patient’s non-adherence to their antibiotic regimens and the resulting contribution to the emergence of antibiotic-resistant bacteria, or superbugs, as well as high direct and indirect costs to the patient and the healthcare system, pose a significant threat to individual and public safety. In light of this threat and armed with the knowledge that it stems from the widespread inadequacies of interventions at the level of patient adherence, healthcare professionals must increase efforts to improve widespread patient adherence initiatives.
     Currently, the most widespread initiative to promote adherence to antibiotic prescription regimens are the Medication Guides/ Consumer Medication information packets mandated by the FDA for most antibiotics that are attached to the packaging of the antibiotic picked up from the pharmacy, or provided in hospital discharge papers. These guides are frequently a single sheet of paper or a small packet. The FDA requires that these guides accompany any drug if it has been determined that “patient adherence to directions for the use of a product are essential to its effectiveness,” and provide information for how to “appropriately use [the] medicine” (7). This intervention falls short of achieving the goal of medication adherence for many reasons, a sampling of which will be examined below.

Medication Guides Fail: Ineffective Use of the Health Belief Model
     The most obvious reason for the ineffectiveness of Medication Guides that stress the importance of antibiotic dosage adherence is that patients simply do not read them. It has even been shown that written information regarding antibiotic regimens does not change compliance among individuals prescribed one or two-dose-a-day antibiotic schedules (4). An examination of the model of health behavior change that Medication Guides are based upon may give us insight into why these are so ineffective. The success of Medication Guides is dependent on the Health Belief Model. According to this theory, patients rationally contemplate an intention to adopt a health behavior by weighing its benefits (affected by perceived susceptibility and severity), costs, and any barriers as perceived by the patient (8). In summary, the Health Belief Model rests upon the idea that if you tell someone that something is bad for their health (high cost), they will act rationally and stop doing it, as well as the converse, that if after weighing the perceived benefits and costs, and the benefits of engaging in an action outweigh the costs, then the individual will adopt the health behavior.
     The paradox that arises with including Medication Guides with antibiotic prescription packaging is that the vast majority of people do not read them so they never get the information that according to the Health Belief Model will supposedly help them make the decision to adhere to their antibiotic dosage regimen. The Health Belief Model assumes that people who are sick will want to do what is best for their health, including reading the medication guide. According to this model, intention leads to behavior, so the intent to get healthy among sick individuals prescribed antibiotics swayed by the knowledge regarding potential consequences of non-adherence, should translate directly into individuals consuming their prescriptions as detailed in the packet. But it is not so simple. People may not be reading the medication guide for many reasons. One such reason is that they may assume they already know the information in the packet. Consequently, they discard it with the other disposable packaging it is attached to.
     The Health Belief Model is also used inappropriately by assuming that individuals who read the Medication Guide will comply, as the Guide does not address the critical part of this theory involving balancing perceived costs and benefits. For example, the Medication Guide for Ciprofloxacin, an antibiotic, lists the most common potential costs, or side effects, including a variety of gastrointestinal distresses and yeast infections (12). Both of these side effects are common in antibiotic use, and the risk for both can be mitigated through widely accepted complementary therapies such as diets including yogurt with active cultures. Medication Guides do not provide an outlet in which patients can actively express their concerns about perceived costs and be engaged in conversation about lessening that burden. Patients also cannot ask questions when simply presented with a Medication Guide regarding the need to take antibiotics past the point of them feeling better, which may be viewed as a nuisance and thus perceived as a cost.

Medication Guides May Invoke Psychological Reactance
     Medication Guides tell people what they have to do which may invoke psychological reactance. Psychological Reactance is a theory based on the immense value that humans attribute to personal freedom. People believe themselves to have “free behaviors” in which to engage (10). When people perceive their free behaviors as threatened, they are motivated into a reactance phase to re-establish their freedom, frequently by doing the opposite of the suggested behavior (10). According to a literature review conducted by Jeanne Fogarty and George Youngs Jr. of North Dakota State University, it has been shown that increased complexity, length, and frequency of medication regimens, all of which correspond to a likelihood of increased threats to freedom, correlate with less adherence to medication dosing (11). The language used in Medication Guides is commanding; for example, the Guide for the antibiotic Ciprofloxacin tells patients to “Take CIPRO exactly as prescribed by your healthcare provider” (12). Simply sharing guides that tell you what to do is not enough to motivate action, and may in fact deter action, as people perceive the unwavering dosage schedule as imposing on their personal freedom.

Medication Guides Fail to Address the Law of Small Numbers and the Law of Optimistic Bias  
     Despite being a legitimate looming public health problem, many individuals do not have any personal experience falling prey to, or knowing someone who has been infected by an antibiotic-resistant superbug. Less than 0.3% of the American population has been infected with an antibiotic resistant bacterium, and less than 0.000000000315% of the population has died from an antibiotic-resistant infection. This makes the odds of patients knowing an individual who had an experience with an antibiotic-resistant infection after not finishing their antibiotics incredibly unlikely (13).
     The Law of Small Numbers describes man’s innate lack of intuition regarding the laws of chance (14-15). People tend to consider a sampling from the population as representative of the whole population, or “local representativeness,” when that is often not the case (14). Because it is far more likely that patients will have had personal experience or know someone who prematurely ended their antibiotic regimen, or decided their own dosing schedule and still recovered fully from their illness than someone who fell prey to a superbug, the vast majority of the US population have the mistaken intuition that their local sampling is representative of the population as a whole. This in turn makes patients less likely to adhere to their prescribed regimen, as they do not intuitively understand the risk that superbugs confer. Medication Guides fail to address the Law of Small Numbers in its entirety, a downfall that needs to be rectified.
     Optimistic Bias, or the theory that when considering personal risk people tend to think they are less likely to be affected than others, is also incredibly prevalent among the population (16). Optimistic bias is problematic because “[it] may seriously hinder efforts to promote risk-reducing behaviors” (16). Even if people do read the Medication Guides, the information provided is often not enough to surmount the optimistic bias many people may experience regarding adhering to their antibiotic dosing regimen. According to this theory, patients will tend to think that they will not be the ones who will have antibiotic resistant drugs breed in them if they prematurely stop taking their drugs or alter their dosing schedules, as individuals tend to underestimate their personal risk even if they understand the legitimacy of the risk at the population level. Medication Guides do not address the consequences of the Law of Optimistic Bias.

An Alternate Approach to an Antibiotic Adherence Initiative: Physician Partnership and the SickBeGone App Intervention
     Paper Medication Guidelines, though serving as an important reminder for proper medication usage, are not sufficient in encouraging adherence to short term antibiotic dosage regimens because they often do not get read and do not provide adequate information to encourage further compliance. In order to correct for the limitations of paper Guidelines I recommend a two-pronged approach. The first part of my approach would involve encouraging physicians to take the time to engage their patients in conversations about their antibiotic treatment regimen options. Many different antibiotics are offered, some of which overlap in their ability to effectively treat the same infections, though present different side effects and require different dosing schedules. When appropriate, physicians should engage their patients in conversation about what their dosing schedule preference is if an option exists. According to the Choice Hypothesis that falls under the umbrella of the Theory of Psychological Reactance, “Patients who are given little or no say in the specification of a regimen will be less likely to comply with medication taking than will patients given the opportunity to exercise some choice over the regimen’s nature, operationalization, or both” (11). It is important for physicians to engage their patients about their preferences with the mindset of partnership, as it has been shown that patients are more compliant with drug prescriptions if physicians present them with a “partnership oriented, advice giving tone” as opposed to an “authoritative tone” (11). Physicians should also actively engage their patients in conversations regarding any barriers that they think would prevent them from being able to take all of their pills, and discuss options for dosage timing to best ensure adherence to the dosage regimen (3). In order to empower patients to take control of their treatment regimen and beat their illness, Physicians should also encourage them to engage in the second part of the proposed intervention, the SickBeGone App.
     I propose the creation of the SickBeGone App, which would be designed and marketed to aid patients in taking control of their illness by creating a supportive social network on the App’s platform and engaging the patient in taking charge of their drug therapy schedule. According to research conducted in partnership with the Hope Lab, technologies such as video games can and have been used successfully in certain patient groups to promote adherence to self-administered medications, suggesting that there is potential for other similar behaviorally targeted technology interventions to be used successfully to enhance adherence (19).
     The patient would download the SickBeGone App by scanning a code that would be printed on their antibiotic pill bottle. Embedded in the code would be a direct link to communicate with the patient’s medical doctor that prescribed the medication, as well as the dosing schedule (for example 3-times-per day for 10 days). Upon scanning the medication bottle with their smart phone, patients would be prompted to choose a start time for their first medication dosage and an alarm of their choosing to remind them to take their pills at the appropriate time of the day. The App would also have a “Help Me Doc” button that patients could press to send a short message directly to their physician’s account about any adverse events they are having or barriers to adherence, with the understanding between both parties that the messages sent via the App will be responded to by the next business day by 10 am to ensure the patient’s needs are met. Additionally, the app would have an “invite” function so that the ill individual could invite their caretakers onto the App’s platform to broaden their support network. The App would let the patients send out messages to their caretakers asking for feel good items such as chicken soup or ginger ale to aid the patient in the healing process. Caretakers could also help manage the patients’ pharmacotherapy adherence via the App. For individuals without smartphones, the SickBeGone platform could also be accessed via a login code printed on the medication container that would allow for the same features, sending email alerts in lieu of alarm reminders. Finally, check-in calls would be offered to patients who have limited access to technology in order to promote antibiotic dosage adherence.
     The App would be advertised via a video message delivered by a woman who is gravely ill. The individual would explain that she has an antibiotic resistant bacterial infection that presented following non-adherence to her antibiotic regimen. The women will tell people how she wishes she took control over her illness when she had the chance, that now the superbugs have won in her and stolen away her health and independence. The advertisement would end with her wishing you well and saying she is glad you have the opportunity to take control over your disease via use of the SickBeGone App.

New Interventions Make Superior Use of the Health Belief Model 
     Several aspects of this proposed two-prong intervention make it more applicable to the Health Belief Model. Numerous interventions that rely on the Health Belief Model have been criticized for ineffectiveness due to many downfalls of this model including lack of realization of the power of social environment. Despite its downfalls in dictating the design for many other public health interventions, several studies that rely on the Health Belief Model for drug adherence programs have shown support for it in promoting adherence to drug regimens (9,20). For example, when physicians have taken the time to educate patients on their conditions and what their prescribed drugs can do for them, patients are more likely to “appreciate the ‘dangerousness’ of [their disease], personal susceptibility to sequelae, the benefits of drug therapy, and the possible negative outcomes of discontinuing the therapy,” making them “significantly more compliant” (9). Conversation helps to lessen perceived costs, which oppose perceived benefits according to this theory, dictating intention and health behavior (8). Instead of assuming patients will read and adhere to the Medication Guides, physicians can help patients increase their adherence to prescribed drug therapies by taking the time to engage them in conversations about their perceived costs, barriers and benefits to therapy, as well as the risks associated with non-adherence.
     The SickBeGone App would also help remove some of the costs to adherence for patients in other ways. The App would provide an easy way for patients to remember to take their drugs on schedule. It would also confer a simplified means of communication with their medical provider should an adverse event arise. This will aid in removing perceived barriers to action among patients, a critical part of the Health Belief Model.

Partnership Attitude Among Physicians and Empowering App Help Avoid Psychological Reactance and Create a Supportive Social Network
     The proposed two-pronged initiative to increase antibiotic prescription adherence is not likely to invoke psychological reactance. Both conversation with patients about what treatment regimens are best for them and the SickBeGone App that empowers patients to take control of their health by preventing them from becoming victims of superbugs help patients manage their treatment by putting them in control of their health outcome. With the Medication Guides’ orders, it was very possible that patients felt as their freedoms are being threatened, which was likely to invoke psychological reactance (11). Psychological Reactance is likely avoided by adopting the two-pronged intervention approach of conversation and the use of the App because it does not take away a freedom, but instead offer’s the patient a sense of control.
     The SickBeGone App also aids in the creation of a social network for patients that helps put them in even further control of managing their health. One study published in Circulation notes how the use of social media networks has the potential to “move health care into a more collaborative endeavor” (21). Platforms like the SickBeGone App have the potential to “empower patients” via the use of more efficient “electronic communication” (22). Patients will now have more direct access to their physicians should adverse events or perceived barriers to adherence arise. They will also have concerted access to their circle of caretakers through the App to promote the patients return to health. Geoffrey Williams aptly reminds us that “autonomy is not independence,” and that the patients “need to feel related to and supported by their providers is an important element in patients feeling able to act autonomously” (24). Patients will feel supported and in control of their health, and therefore are more likely to properly complete their therapy regimen.

Marketing Theory and Framing Theory Use to Counter the Law of Small Numbers and Optimistic Bias
     The App will be promoted with an advertising campaign that adopts the core value of freedom. By framing the adherence issue using a Freedom frame, urging patients to not let superbugs dictate their life but instead to take control of their own health, the App will gain legitimacy and popularity. A frame is defined as “a way of packaging and positioning an issue so that it conveys a certain meaning,” and its power lie in its ability to “‘steer public and political support in the desired direction’” (25). By packaging antibiotic adherence as an issue of maintaining an individual’s freedom, which is a “compelling core value”, an emotional response is brought about in the individual, promoting support of initiatives to maintain this freedom (in our case antibiotic adherence interventions) (25). As more people see the advertisement with a patient who has fallen prey to an antibiotic resistant bacteria described above, the effect of the law of small numbers and optimistic bias will decrease. More exposure to the true severity of non-adherence will make the threat seem more real and prevalent than it is currently viewed, thus giving individuals a better sense of the probability of dangerous superbugs emerging as well as the actual personal risks that exist as a result of non-adherence.

     The widespread promotion of improved antibiotic adherence interventions is already late in its arrival to the forefront of Public Health issues. The need for new interventions such as the one suggested above is critical to reduce the emergence of antibiotic-resistant bacteria and to reduce both direct and indirect costs incurred by patients and the health care system in managing superbug infections. By realizing the need to improve this largely neglected component of antibiotic treatment, we are already taking a step in the right direction. Antibiotic prescription adherence interventions need to make appropriate use of models such as the Health Belief Model that already have been shown to work in medication adherence initiatives. These interventions will be most effective if they are augmented by the avoidance of psychological reactance, if they address patients’ tendency towards optimistic bias, and finally if they confront patients’ innate lack of understanding of the risk of antibiotic-resistant bacteria emergence. Campaigns such as the one described for the proposed physician endorsed SickBeGone App offer a simple and elegant way to integrate adherence into the technology-based world we are coming to live in. If we are to continue in a world where antibiotics work in defending us from bacterial infections, we need to institute interventions that address antibiotic adherence far more directly and effectively than the archaic method of stapling a Medication Guide to the packaging of the pills.

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