Nonadherence in Outpatient Thromboprophylaxis after Major Orthopedic Surgery: A Systematic Review

After Major Orthopedic Surgery: A Systematic Review

Thomas Wilke; Sabrina Müller


Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(6):691-700. 

In This Article


Medication-based NA (alternatively referred to as 'noncompliance'), in general, can be defined as the extent to which a person's drug-taking behavior does not correspond with recommendations from a healthcare provider.[20] For this reason, studies that concern themselves with the adherence to evidence-based guidelines provided for medical doctors are not part of NA research according to the definition followed here. By contrast, a prescription recommended by a medical doctor concerning a specific medication and including the dosage and length of the medication period is the starting point of our NA research.

There is a lack of complete agreement among academics regarding how NA should best be measured. The measurement of medication-based NA can be acheived in different ways (Figure 2). The most frequently used techniques are to employ administrative data and self-report measures. Each of the listed indicators has advantages and disadvantages, so that the ideal choice can only be made on the basis of the goals of a particular study and the availability of data. As all the measures have weaknesses, reliable measurement requires that a multi-indicator method be used.[20,21]

Figure 2.

Methods for nonadherence measurement.
Examples: Morisky-4-item [39]; Morisky-8-item [40]; Medication Adherence Report Scale (MARS) [41]; Hill-Bone [42]; Adherence to Refills and Medications Scale (ARMS) [43]; ASK-20 [44].
Examples: Brief Adherence Rating Scale (BARS; schizophrenia) [45]; 28-item Iron Chelation Therapy Questionnaire [46]; ITAS [47]. CMG: Continuous measure of medication gaps; ITAS: Immunosuppressant therapy adherence instrument; MEMS: Medication event monitoring system; MPR: Medication possession ratio; NA: Nonadherence; NP: Nonpersistence; PDC: Percentage of days covered. Data taken from: Institut für Pharmakoökonomie und Arzneimittellogistik (IPAM); most of the shown instruments are described in [48,49].

Studies dealing with possible NA during the medication-based treatment of ambulant thrombosis prophylaxis can be classified by means of six central features. The first is the medication on which the study is based. This is of particular importance because different medications require different application techniques and these, at least potentially, influence the adherence of the patients. The second important criterion is the issue of whether the collection of the patients' adherence data takes place in a routine context or not. By routine context, we mean the normal daily patient care routine followed by medical staff. Unusual features in a study, such as newly introduced patient education programs, particular data collection instruments capable of affecting the patients' perceptions of NA and, in general, the detailed description of the study goals to the patients involved, cause a bias towards an analysis of adherence that is probably too positive. The third classification feature is how possible NA is measured and whether – as required by the adherence literature – multi-indicator concepts are used. Fourth, studies differ with respect to the length of the thromboprophylaxis period that is analyzed, and this fact can be utilized for classification purposes. Fifth, whether or not the extent of the NA (measured by noninjection days as a percentage of all injection days) is measured is an important feature when distinguishing between studies. Sixth, studies differ in whether they record possible NA reasons.

In most of the adherence literature that is related to chronic indications, a patient is still considered to be adherent if that patient takes the medication 80% of the time. There is also a certain amount of empirical evidence to support the existence of this threshold.[22] However, in thromboprophylaxis studies, there appears to be no clear evidence regarding how many daily prophylaxis doses have to be missed by patients before a significantly increased risk of thrombosis/pulmonary embolism results.[23,24] Therefore, in this case, there is no clinically based NA threshold on which to divide patients into adherent and nonadherent groups. That is why, in most of the publications dealing with NA in outpatient thrombosis prophylaxis, a nonadherent patient is conservatively defined as a patient who has not taken the medicine on at least 1 day even though the treating clinic/doctor has recommended daily thrombosis prophylaxis.

We conducted a systematic literature review using Medical Literature Analysis and Retrieval System Online (MEDLINE) and the Excerpta Medica Database (EMBASE), covering publications from 1 January 1990 until 30 April 2010. The key terms used included: [adherence, compliance, concordance, persistence] AND [heparins, low molecular weight heparin, unfractionated heparin, thrombosis prophylaxis, thromboprophylaxis]. We also manually searched the reference lists of the articles that were identified in the initial search, and also included those references that were relevant to our research terms.

Studies that reported research regarding NA in outpatient thrombosis prophylaxis after major orthopedic surgery were included. No further criteria concerning the quality of the studies or the type of prophylaxis that preceded the operation were included. Abstracts and full publications were reviewed by the two authors and disagreements were resolved by consensus. The extracted information included the study design, the specific care context of the analysis, sample size, the main study objective, the duration of analyzed thrombosis prophylaxis in days, medication and NA measures used, and results regarding NA rates and NA reasons.


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