We don’t know how to improve medicine adherence, says new Cochrane review


Most people who have been prescribed medications at least at some point during the course of treatment wonder whether continuing really makes sense and whether they should not simply stop altogether.

Other, non-intentional factors, such as simple lapses of memory, also contribute to what is generally termed low “treatment adherence”.

It comes as no surprise, therefore, that people often only take half of the prescribed dose, which reduces the efficacy of the medication and hinders treatment success.

A recent Cochrane Review (Nieuwlaat et al, 2014) has now taken a look at interventions aiming to improve treatment adherence.


The reviewers screened important databases, including EMBASE and PsycINFO, for studies with participants receiving medication for any medical condition except addiction. Specifically, randomised controlled trials (RCTs) that assessed both medication adherence as well as clinical outcome and at least 80% follow-up. For long-term treatments, a follow-up of at least six months was required. In addition, risk of bias was assessed with a view to study design, participant allocation and blinding.

The reviewers found high heterogeneity among relevant studies in terms of medical condition, patient population and adherence measure. They decided to conduct a qualitative analysis of methodologically suitable RCTs rather than a meta-analysis.


A total of 182 RCTs with 46,962 participants were included in the paper.

The most prominent conditions were HIV/AIDS (36 studies), psychiatric disorders (29 studies) and chronic obstructive pulmonary disease (27 studies) and treatment most commonly included more than one drug.

Overall, there was high heterogeneity in terms of settings, clinical disorders, treatment regimens, adherence interventions and measures. Also, risk of bias varied considerably among studies and overall only 17 studies were considered as having a low risk of bias.

These “high-quality” investigations:

  • Generally employed several means of ongoing support from family, peers or health professionals such as pharmacists who provided education, counselling and/or daily treatment support
  • Included five RCTs that found improved adherence as well as clinical outcome, while three RCTs found only improved adherence and one RCT found that the employed intervention only improved clinical outcomes
  • Included eight RCTs that showed no effect of the intervention on either treatment adherence or clinical outcomes
  • More modern approaches such as sending text reminders were not consistently shown to improve adherence
  • “Complex interventions” that relied on health care providers as well as family and peers were the most common interventions

However, the authors caution that criteria of intervention success varied substantially among studies, which means that it remains challenging to draw definite conclusions from these figures.

Complex interventions

Complex interventions that involved health professionals, family members and peers were the most common in the review.


  • As is consistently lamented throughout the manuscript, there was considerable variation in terms of study design, methodology, participants, medical illness and setting. This makes it difficult to derive meaningful conclusions.
  • In addition, owing to substantial risk of bias in some studies, the authors decided to focus on the 17 studies with the lowest risk of bias, which means that relaxed inclusion criteria could have led to a different outcome.
  • Of note, most studies recruited participants based on their willingness to take part in the study, rather than showing low adherence. Potentially, this could have made it more difficult to detect an effect on adherence.
  • In addition, most studies relied on self-report measures of adherence, which is infamous for several biases and overestimation (Haynes et al., 1980), and small numbers of participants.

The reviewers found that the included RCTs were too varied to draw any meaningful conclusions.


The authors conclude that:

Across the body of evidence, effects were inconsistent from study to study, and only a minority of lowest risk of bias RCTs improved both adherence and clinical outcomes. Current methods of improving medication adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realised.


Effective ways to increase adherence to beneficial drug regimens are still broadly missing, which means that patients often fail to capitalise on a medication’s benefits.

As this review points out, more refined research strategies are needed to improve the situation for patients and clinicians. Specifically, Nieuwlaat et al. (2014) highlight three main concerns for future studies:

  1. Long-term interventions with improved design
  2. More objective and accurate measures of adherence
  3. Increased sample size

With these points in mind, there is still a long way to go.

Only five of these RCTs improved both medicine adherence and clinical outcomes, and no common characteristics for their success could be identified

Only 5 of the 17 “low risk” RCTs improved both medicine adherence and clinical outcomes, and no common characteristics for their success could be identified.


Nieuwlaat R, Wilczynski N, Navarro T, Hobson N, Jeffery R, Keepanasseril A, Agoritsas T, Mistry N, Iorio A, Jack S, Sivaramalingam B, Iserman E, Mustafa RA, Jedraszewski D, Cotoi C, Haynes RB. Interventions for enhancing medication adherence. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD000011. DOI: 10.1002/14651858.CD000011.pub4.

Haynes, R. B., Taylor, D. W., Sackett, D. L., Gibson, E. S., Bernholz, C. D., & Mukherjee, J. (1980). Can simple clinical measurements detect patient noncompliance? Hypertension, 2(6), 757–64. [PubMed abstract]

Share on Facebook Tweet this on Twitter Share on LinkedIn Share on Google+