Adherence is a primary determinant of the effectiveness of treatment (4,5) because poor adherence attenuates optimum clinical benefit (6,7). Good adherence improves the effectiveness of interventions aimed at promoting healthy lifestyles, such as diet modification, increased physical activity, non-smoking and safe sexual behaviour (8-10), and of the pharmacological-based risk-reduction interventions (4,11-13). It also affects secondary prevention and disease treatment interventions.
For example, low adherence has been identified as the primary cause of unsatisfactory control of blood pressure (14). Good adherence has been shown to improve blood pressure control (15) and reduce the complications of hypertension (16-18). In Sudan, only 18% of nonadherent patients achieved good control of blood pressure compared to 96% of those who adhered to their prescribed treatment (19,20).
In studies on the prevention of diabetes type 2, adherence to a reduced-fat diet (21) and to regular physical exercise (22) has been effective in reducing the onset of the disease. For those already suffering the disease, good adherence to treatment, including suggested dietary modifications, physical activity, foot care and ophthalmological check-ups, has been shown to be effective in reducing complications and disability, while improving patients' quality of life and life expectancy (23).
Level of adherence has been positively correlated with treatment outcomes in depressed patients, independently of the anti-depressive drugs used (24). In communicable chronic conditions such as infection with HIV, good adherence to therapies has been correlated with slower clinical progression of the disease as well as lower virological markers (25-32).
In addition to their positive impact on the health status of patients with chronic illnesses, higher rates of adherence confer economic benefits. Examples of these mechanisms include direct savings generated by reduced use of the sophisticated and expensive health services needed in cases of disease exacerbation, crisis or relapse. Indirect savings may be attributable to enhancement of, or preservation of, quality of life and the social and vocational roles of the patients.
There is strong evidence to suggest that self-management programmes offered to patients with chronic diseases improve health status and reduce utilization and costs. When self-management and adherence programmes are combined with regular treatment and disease-specific education, significant improvements in health-promoting behaviours, cognitive symptom management, communication and disability management have been observed. In addition, such programmes appear to result in a reduction in the numbers of patients being hospitalized, days in hospital and outpatient visits. The data suggest a cost to savings ratio of approximately 1: 10 in some cases, and these results persisted over 3 years (33). Other studies have found similarly positive results when evaluating the same or alternative interventions (28,34-47).
It has been suggested that good adherence to treatment with antiretroviral agents might have an important impact on public health by breaking the transmission of the virus because of the lower viral load found in highly adherent patients (12).
The development of resistance to therapies is another serious public health issue related to poor adherence, among other factors. In addition to years of life lost due to premature mortality and health care costs attributable to preventable morbidity, the economic consequences of poor adherence include stimulating the need for ongoing investment in research and development of new compounds to fight new resistant variants of the causative organisms.
In patients with HIV/AIDS, the resistance of the virus to antiretroviral agents has been linked to lower levels of adherence (29) by some researchers, while others have suggested that resistant virus is more likely to emerge at higher levels of adherence (48,49). Although they appear to be contradictory, both describe the same phenomenon from a different starting point. At the lower end of the spectrum of adherence, there is insufficient antiretroviral agent to produce selective pressure, so the more adherence rates increase the higher the likelihood that resistance will appear. At the higher levels of adherence, there is not enough virus to become resistant, thus the less adherent the patient, the greater the viral load and the likelihood of resistance. Some of the published research has suggested that when adherence rates are between 50% and 85%, drug resistance is more likely to develop (50,51). Unfortunately, a significant proportion of treated patients fall within this range (52). The "chronic" investment in research and development could be avoided if adherence rates were higher, and the resources could be better used in the development of more effective and safer drugs, or by being directed to the treatment of neglected conditions.
There is growing evidence to suggest that because of the alarmingly low rates of adherence, increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments (53).
We strongly support the recommendations of the Commission on Macroeconomics and Health on investing in operational research "at least 5% of each country proposal for evaluating health interventions in practice, including adherence as an important factor influencing the effectiveness of interventions" (12).