Abstract
Scientific background
Poor compliance or adherence in drug therapy can cause increased morbidity, mortality and enormous costs in the healthcare system (in Germany annually approximately 10 billion euros). Different methods are used for enhancing the compliance or adherence.
Research questions
The evaluation addresses the questions about existence, efficacy, cost-benefit relation as well as ethical-social and juridical implications of strategies for enhancing compliance or adherence in drug therapy with concomitant improvements in treatment outcomes.
Methods
A systematic literature search was conducted in the medical, also health economic relevant, literature databases in January 2007, beginning from 2002. Systematic reviews on the basis of (randomised controlled trials (RCT) concerning interventions to enhance compliance or adherence with regard to treatment outcomes as well as systematic reviews of health economic analyses were included in the evaluation. Additionally, it was also searched for publications which primarily considered ethical-social and juridical aspects of these interventions for the German context.
Results
One systematic review with data for 57 RCT was included in the medical evaluation and one systematic review with data for six studies into the health economic evaluation. No publication primary concerning ethical-social or juridical implications could be identified.
A significant positive effect on the treatment outcome was reported for 22 evaluated interventions. For many interventions the results can be classified as reliable: counseling with providing an information leaflet and compliance diary chart followed by phone consultation for helicobacter pylori positive patients, repeated counseling for patients with acute asthma symptoms, telephone calls to establish the level of compliance and to make recommendations based on that for the therapy of cardiovascular diseases, calls of an automated telephone system with phone counseling in problem cases for diabetics, different family based interventions including repeated family counseling, education and "culturally modified family therapy" in patients with schizophrenia, repeated "compliance therapy" sessions for patients with acute psychosis. For other interventions the results should be viewed with more concern (because of the poor methodical quality of the underlying studies). The effect size of the interventions can not be estimated from the available data.
From the available data, no reliable results can be provided concerning the cost-benefit relation of these strategies.
Discussion
Many of the reported studies had a poor reporting and methodological quality. The reliability of the conclusions of the studies is restricted because of methodical shortcomings. Efficacy and cost estimates determined in the health economic studies are not transferable to the current situation in Germany. It has been discussed recently that the compliance or adherence enhancing interventions can restrict the autonomy and the privacy of the patients.
Conclusions
In drug therapy some compliance or adherence enhancing interventions with concomitant positive effect on the treatment outcome may be used. The cost-benefit relation of these interventions is to be estimated. Using these interventions the patient’s autonomy and privacy are to be restricted as few as possible.
Abstract
Wissenschaftlicher Hintergrund
Mangelnde Compliance bzw. Adherence in der Arzneimitteltherapie kann erhöhte Morbidität, Mortalität und gewaltige Kosten im Gesundheitssystem verursachen (in Deutschland jährlich ca. 10 Milliarden Euro). Es werden verschiedene Methoden zur Verbesserung der Compliance bzw. Adherence eingesetzt.
Fragestellungen
Es stellt sich die Frage nach Vorhandensein, Wirksamkeit, Kosten-Nutzen-Relation sowie nach ethisch-sozialen und juristischen Implikationen von Strategien zur Beeinflussung der Compliance bzw. Adherence mit Verbesserung des Therapieerfolgs bei der medikamentösen Therapie.
Methodik
Eine systematische Literaturrecherche wurde im Januar 2007 in den medizinischen, darunter auch gesundheitsökonomisch relevanten, elektronischen Datenbanken ab 2002 durchgeführt. Es wurden systematische Übersichten auf der Basis von randomisierten kontrollierten Studien (RCT) über Interventionen zur Beeinflussung der Compliance bzw. Adherence mit Hinblick auf den Therapieerfolg sowie systematische Übersichtsarbeiten von Studien mit gesundheitsökonomischen Analysen in die Bewertung einbezogen.
Es wurde außerdem nach Publikationen mit expliziter Betrachtung von ethisch-sozialen und juristischen Aspekten dieser Maßnahmen für den deutschen Kontext gesucht.
Ergebnisse
Es wurde eine systematische Übersichtsarbeit mit Angaben für 57 RCT in die medizinische und eine mit Angaben für sechs Studien in die gesundheitsökonomische Bewertung einbezogen; es konnte keine Publikation zu ethisch-sozialen und juristischen Implikationen identifiziert werden.
Bei 22 untersuchten Maßnahmen wurde über einen signifikanten positiven Effekt auf den Therapieerfolg berichtet. Bei mehreren Interventionen sind diese Ergebnisse als verlässlich einzustufen: Beratung mit Aushändigung eines Tagebuchs zur Compliance mit anschließendem Telefonanruf bei Helicobacter pylori positiven Patienten, wiederholte Beratungen von Patienten mit akuter Asthmasymptomatik, Telefonanrufe zur Erfassung der Compliance und Abgabe daran orientierter Empfehlungen bei der Therapie kardiovaskulärer Erkrankungen. Dies galt ebenfalls für Anrufe von einem automatischen telefonischen System sowie telefonische Beratung von Diabetikern bei Problemfällen, verschiedene Maßnahmen der Familientherapie einschließlich Beratung und Schulung der Familienangehörigen sowie „kulturell modifizierte Familientherapie“ bei Patienten mit Schizophrenie, ebenso für wiederholte „Compliance Therapie“-Sitzungen bei Patienten mit akuter Psychose.
Bei anderen Interventionen sind die Ergebnisse mit etwas größeren Bedenken (wegen schlechterer methodischer Qualität der zugrunde liegenden Studien) zu betrachten. Die Stärke des Effekts der Maßnahmen ist aus den vorliegenden Informationsquellen nicht abzuschätzen.
Aus den vorliegenden Daten konnten keine zuverlässigen Ergebnisse zur Kosten-Nutzen-Relation dieser Strategien ermittelt werden.
Diskussion
Viele der berücksichtigten Studien litten an mangelnder Berichts- und Studiendurchführungsqualität. Die Verlässlichkeit der Studienaussagen ist durch die methodischen Mängel eingeschränkt. Die in den gesundheitsökonomischen Studien ermittelten Wirksamkeits- und Kostenschätzer sind nicht auf die aktuelle Situation in Deutschland übertragbar. Es wird diskutiert, dass die Compliance bzw. Adherence fördernden Maßnahmen die Unabhängigkeit und Privatsphäre der Patienten einschränken können.
Schlussfolgerungen
In der Arzneimitteltherapie können Compliance bzw. Adherence fördernde Maßnahmen mit positivem Effekt auf den Therapieerfolg angewendet werden. Die Kosten-Nutzen-Relation dieser Maßnahmen sollte noch untersucht werden. Aus ethischer und sozialer Sicht sind die Patientenunabhängigkeit und -privatsphäre beim Einsatz dieser Interventionen so wenig wie möglich einzuschränken.
Executive Summary
1. Scientific background
Compliance is defined as the extent to which patients follow medical instructions. In contrast adherence is determined as the extent of the conformance between the actual and with the health care provider agreed patient’s behavior.
Measurements of the compliance or adherence in drug therapy can be divided in various ways, for example into objective, biochemical, subjective and clinical methods. In general, direct and indirect methods are to be distinguished.
Several factors affect the compliance or adherence. In June 2003, the World Health Organization (WHO) stated five dimensions of adherence affecting factors: condition, therapy, patient, social/economic and health system.
The WHO estimates the degree of compliance or adherence in developed countries to be about 50%. Good compliance or adherence is considered to be associated with improved effectiveness of medical interventions, poor compliance or adherence with increased morbidity and mortality.
Poor compliance or adherence can cause enormous costs in the healthcare system. In Germany, medical costs due to poor compliance in drug therapy are estimated to be up to 10 billion euros annually. They are supposed to be in the range of the expenditures for major diseases such as coronary heart disease. Due to demographic change, the burden of chronic diseases in Germany is expected to increase until 2020, therefore the Non-Compliance or Non-Adherence problem is also supposed to become more crucial.
Different methods are used for enhancing the compliance or adherence. These interventions can address each of the five dimensions:
Condition affecting interventions: for example identification and treatment of compliance or adherence influencing co-morbidities (depression, gastritis).
Therapy affecting interventions: for example selection of the appropriate pharmaceutical dosage form, drug packaging, simplifying of the dosage, and development of drugs with an improved side-effect profile.
Patient affecting interventions: Interventions to improve the patient knowledge, motivation and skills to influence its illness positively (patient education, training, counseling etc.) as well as reminders (alarms, calendars, letters, prospects, phone calls, e-mails etc.).
Social/economic aspects affecting interventions: for example social support (relatives, self-help groups), reducing the price or the co-payments for medicines, improvement of the health education, simplification of the access to medical care.
Health system affecting interventions: for example improvement of the physician-patient-relationship, continuing education of the physicians, creation of financial incentives for healthcare providers to carry out compliance or adherence enhancing interventions as well as reduction of overwork.
2. Research questions
Medical evaluation
Which compliance or adherence enhancing strategies in drug therapy exist, that concomitantly improve treatment outcomes? How effective are these strategies with regard to the treatment outcomes?
Health economic evaluation
What are the cost-utility-relations of the compliance or adherence enhancing strategies which concomitantly improve treatment outcomes in drug therapy?
Ethical-social and juridical aspects
Which ethical-social and juridical implications are to be considered in the implementation of the compliance or adherence enhancing interventions with concomitant improvement of the treatment outcomes in drug therapy?
3. Medical evaluation
3.1 Methods
The systematic literature search was conducted in the medical electronic databases and was restricted to publications beginning from 2002 as well as to the languages German and English. Only published data were included in the medical evaluation.
The selection of the literature was performed in three steps: evaluation of the titles, abstracts and of the full text. Two independent reviewers were involved in the selection of the relevant publications.
Systematic reviews on the basis of randomised controlled trials (RCT), which compared compliance or adherence enhancing interventions to no intervention or different of these interventions among each other were included in the evaluation. Moreover these reviews should consider the effects of the compliance or adherence enhancing interventions on the treatment outcomes.
3.2 Results
The literature search was conducted in January 2007 and resulted in 1569 hits. 74 publications were selected to be examined in full text and one systematic review with data for 57 RCT was included in the evaluation.
A significant positive effect on the treatment outcome has been reported for 22 evaluated interventions.
The results for the following interventions were classified as reliable:
counseling with providing of an information leaflet and compliance diary chart followed by phone consultation for helicobacter pylori positive patients,
repeated counseling for over 18 years old patients with acute asthma symptoms,
telephone calls to establish the level of compliance and to make recommendations based on that for the therapy of cardiovascular diseases,
calls of an automated telephone system with phone counseling in problem cases for under 75 years old diabetics,
different family based interventions in patients with schizophrenia including repeated family counseling, education programs and "culturally modified family therapy",
repeated "compliance therapy" sessions for stationary patients with acute psychosis.
The results for effectiveness of the following interventions should be considered with more concern (because of the poor methodical quality of the underlying studies):
specific counseling and providing of written instructions for parents of under 15 years old children with streptococcal pharyngitis,
a brief training and providing of written instructions on how to use the spray (with or without additional slide presentation) for patients with pollen allergy,
twice a day intake of controlled-released niacin (vs. four times a day intake of regular niacin) in men under 65 years with high risk for coronary heart disease,
a program composed on providing of information pamphlets, personal counseling, visits of a support group and phone call for over 18 years old patients with expiratory wheezing,
a pharmaceutical care program for patients with asthma or chronic obstructive pulmonary disease,
a program composed of individualized counseling, adaptation of treatment to the patient’s lifestyle, phone support (for questions) and monthly visits of the day clinic for HIV-patients (HIV=Human Immunodeficiency Virus),
a program consisted of education, providing of video and written information, home visits, telephone monitoring, personalized mails according to personal relapse prevention plan for patients with depression or anxiety disease.
The most common thread of the most interventions was more frequent interaction of health care providers with patients in the course of therapy and attention paid to compliance or adherence.
The effect size of the compliance or adherence enhancing interventions on the treatment outcomes can not be estimated from the available data.
3.3 Discussion
Although the interventions carried out in the primary studies were briefly presented in the underlying systematic review the exact contents and the quality of the interventions can only be judged in a limited way. Moreover, it is not always clear from the studies description, which publications comprise compliance and which adherence enhancing interventions.
Many of the reported studies had a poor report quality concerning the considered interventions. Especially in studies published until 1998 the data concerning the patient allocation concealment into the study groups are missing.
Many studies use patient’s self-reporting of the drug consumption for the estimation of the compliance or adherence. Sometimes also very inexact parameters are used for the measurement of the treatment outcomes. In many studies there is also a lack of information on patient’s blinding. The reliability of the conclusions of the studies is restricted due to the mentioned methodical shortcomings.
4. Economic evaluation
4.1 Methods
A systematic literature search was conducted in the medical also health economic relevant databases (described in the medical evaluation). Similar to the medical evaluation, the analysis of the literature search was carried out in three steps.
Systematic reviews of health economic analyses which compared compliance or adherence enhancing interventions to no intervention or different of these interventions among each other were included in the evaluation.
4.2 Results
The literature search was conducted in January 2007 and resulted in 1448 hits. 51 publications were selected to be examined in full text and one systematic review with data for six studies into the health economic evaluation.
From the available data, no reliable results could be provided concerning cost-benefit relation of strategies for enhancing compliance or adherence in drug therapy with concomitant improvement in treatment outcomes.
4.3 Discussion
The literature search which was conducted in the evaluated systematic review in 2000 is not complete and not up-to date. The description of the studies included in this review is extremely bad. The design, methodical quality of the evaluated studies as well as details of the provided interventions can only be appraised approximately from the presented description.
The evaluated studies showed many shortcomings. Clinical estimates were derived from obsolete information sources of low evidence and no study met the requirements of RCT. No study used cost estimates for the compliance or adherence enhancing interventions in euros or referred to interventions in the German health care system. Cost estimates were generally derived in the time before 2000. Therefore, the transferability of the efficacy and cost estimates determined in these studies to the current situation in Germany is limited.
5. Ethic, social and juridical aspects
5.1 Methods
In the course of the conducted systematic review it was also searched for publications which primarily considered ethical-social and juridical aspects of these interventions for the German context (data on information sources and search strategy are presented in medical evaluation).
5.2 Results
The literature search was performed in January 2007 and resulted in eleven hits. Two publications were selected to be examined in full text. No publication concerning ethical-social or juridical implications could be included in the evaluation. The hand search in the internet yielded no relevant hits.
5.3 Discussion
Although no relevant publication to ethical-social aspects could be identified from the conducted literature search, it has been discussed recently, that the compliance or adherence enhancing interventions can restrict the autonomy and the privacy of the patients. The access to effective compliance or adherence enhancing interventions for some social groups may be limited.
6. Summary discussion of all results
Previously published studies were predominantly focused on patient- or therapy-related factors of the compliance or adherence. The health care system has also an essential impact on compliance or adherence. Health care system directed interventions were not appropriately evaluated yet.
7. Conclusions
Some compliance or adherence enhancing interventions in drug therapy with improvement in treatment outcomes may be used. To implement any intervention by healthcare providers its description in the primary study should be considered.
No conclusions about the cost-utility-relation of the compliance or adherence enhancing interventions in drug therapy can be drawn from the existing data. The cost-utility relations should be estimated in high-value health economic evaluations (studies or models).
Using compliance or adherence enhancing interventions the patient’s autonomy and privacy are to be restricted as few as possible. The access to these interventions should be guaranteed for all social groups.