Elsevier

Cancer Treatment Reviews

Volume 40, Issue 1, February 2014, Pages 102-108
Cancer Treatment Reviews

Anti-Tumour Treatment
Adherence enhancing interventions for oral anticancer agents: A systematic review

https://doi.org/10.1016/j.ctrv.2013.07.004Get rights and content

Abstract

Background

The use of oral anticancer agents has increased in the last decades. Adherence is a crucial factor for the success of oral anticancer agent therapy. However, many patients are non-adherent.

Objective

The objective was to evaluate the effectiveness of adherence interventions in patients taking oral anticancer agents.

Methods

A systematic literature search was performed in Medline and Embase. Titles and abstracts and in case of potential relevance, full-texts were assessed for eligibility according to the predefined inclusion criteria. The study quality was evaluated. Both process steps were carried out independently by two reviewers. Relevant data on study design, patients, interventions and results were extracted in standardized tables by one reviewer and checked by a second reviewer.

Results

Six controlled studies were included. Only one study was randomized. The study quality was moderate to low. One study showed statistically significant results in favor of the adherence intervention, two studies showed a tendency in favor of the intervention, one study showed an inconsistent result depending on the adherence definition and one study showed almost identical adherence rates in both groups. One study showed a tendency in favor of the control group.

Conclusions

Although most of the interventions are not very effective, it appears that certain adherence enhancing interventions could have a promising effect. One crucial point is the consideration of the baseline adherence when choosing patients to avoid ceiling effects. The evidence is limited due to lack of sufficient studies and partly inconsistent results. Further high quality studies are needed.

Introduction

The use of oral anticancer agents (OACA) has increased in the last decades. It is assumed that one quarter of newly developed anticancer agents could be taken orally [1] and the amount of oral therapy in cancer treatment will probably increase further. Adherence, defined as “the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen [2],” is lower in patients taking OACA compared to patients taking intravenous chemotherapy [3]. Adherence rates in cancer patients range from less than 20–100%, depending on patient characteristics, therapy and adherence measurement/definition [4], [5]. Most patients prefer to take their medication orally [6]. Adherence is one predisposing factor for the success of OACA [7], [8], in particular when considering the long period in which OACA have to be taken correctly. Thus, adherence has become an important issue in modern oncology treatment.

However, several factors (patient characteristics, treatment characteristics, disease characteristics, setting) exist, for which an influence on patient adherence in patients taking OACA has been shown [9]. The factors can be roughly divided in the following five dimensions: Social and economic, health care system, health condition, therapy and patient [10].

Social and economic factors are all factors concerning the social an economic status of a person. For example, poverty and income can result in conflicting priority-setting regarding the use of limited resources. The consequence can be that adherence is reduced because the priority for other demands than medications (e.g., food) is perceived higher.

Health care system factors are all factors that relate to the organizational structures of the health care system/services and characteristics of the health care professionals. This includes e.g., the coverage of health insurance, patient-provider relationship or medication distribution.

Health condition related factors are all factors that affect the patient regarding certain disease. These include the severity of disease, severity of symptoms, prognosis or availability of effective treatments.

Therapy related factors are factors that relate to a certain therapy like the regime complexity or adverse events.

Patient factors are related to the patient attitudes, knowledge, beliefs, perceptions and expectations. For example the health literacy or beliefs about cure [10].

Different types of interventions to enhance patient adherence can be applied that target one or multiple of the five described adherence influencing dimensions. The potential of interventions to enhance adherence is probably raised by simultaneously targeting several of the influencing dimensions. But the effectiveness of an adherence enhancing intervention depends not only on the intervention itself but also on the applicability for a specific patient group.

On the one hand, many adherence interventions exist for chronic conditions for which a statistically significant influence on patient adherence as well as on clinical outcomes was proven. On the other hand, there are many ineffective interventions [11].

To the best of our knowledge only one review investigating interventions to enhance patient adherence for OACA exists [12]. This review was not prepared systematically. Furthermore as adherence is meanwhile an often discussed issue in OACA therapy, it could be expected that the review don’t cover all relevant studies on this topic that have been probably published in the last five years.

The objective of this systematic review was to identify and summarize all controlled studies examining the effectiveness of adherence enhancing interventions for adult patients taking OACA.

Section snippets

Search strategy

A systematic literature search was performed in the databases Medline (via Pubmed) and Embase (via Embase excluding Medline records). The search strategy combined various synonyms, antonyms, acronyms and medical subject headings related to adherence, oncology as well as OACA and was adapted for each database (the full search strategies are available in Appendix I). The search was performed in December 2012. We did not limit the publication date and language in the search strategy.

Study selection

To be eligible

Results

The literature search resulted in 2309 hits after electronic removal of duplicates. Ninety-five titles and abstracts were rated as potentially relevant for and the full-texts were screened. In this process step 88 publications were rated as irrelevant. Seven publications satisfied all inclusion criteria. Two studies seemed to be based in great part on the same participants [15], [16]. The authors were contacted and confirmed the assumption. Thus, six studies (seven publications) were included.

Discussion

This is the first review that systematically analyzes the effectiveness of adherence enhancing interventions in cancer care. Six studies were included. One study showed statistically significant results in favor of the adherence intervention [21]. Three studies showed the tendency in favor of the intervention groups [13], [14], [18], [19]. Whereas in two studies results were inconsistent regarding statistical significance depending on the adherence definition [15], [16], [18]. But is should be

Conclusion

Drawing a clear conclusion is difficult because of the low level of evidence/study design and low methodological study quality. However, it seems that adherence enhancing interventions could have an effect, if the baseline adherence is considered when choosing eligible patients to avoid ceiling effects. Especially educational and counseling interventions seem promising. A reason could probably be that educational and counseling interventions mostly target several of the adherence influencing

Conflict of interest

This work was funded by Janssen-Cilag Germany. There is no other conflict of interest.

Funding

This work was funded by Janssen-Cilag Germany. The sponsor has no influence on the study design, and in the collection, analysis and interpretation of data. Janssen-Cilag Germany has reviewed the manuscript and provided comments. The final decision to include the comments and the decision to submit the manuscript for publication was made only by the authors.

Authorship

All authors have made substantial contributions and approved the conceptions, drafting, and final version of the manuscript.

References (26)

  • World Health Organization. Adherence to long-term therapies: evidence for action;...
  • R.B. Haynes et al.

    Interventions for enhancing medication adherence

    Cochrane Database Syst Rev

    (2008)
  • K. Ruddy et al.

    Patient adherence and persistence with oral anticancer treatment

    Cancer J Clin

    (2009)
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