Whether people with Alzheimer's disease benefit in the long term from non-drug treatment interventions remains an unanswered question.
This unsatisfactory finding is mainly due to the fact that convincing studies are lacking so far. For individual approaches, the studies provide indications of a benefit, but also of harm. This is the conclusion of a report by the German Institute for Quality and Efficiency in Health Care, Cologne, which was published in March 2009 and for which an English-language summary is now available.
According to IQWiG, a general problem of the benefit assessment of non-drug treatment interventions is particularly shown in the therapy of Alzheimer's disease: small research budgets and an underdeveloped study methodology lead to the situation that even for procedures with potential, no reliable conclusions can be drawn and thus no proof of a benefit can be provided.
Alleviate accompanying symptoms, strengthen competence in daily activities
The needs of patients with Alzheimer's disease are complex and change with disease progression. The treatments developed so far are just as varied; in addition to drugs, non-drug interventions are also used. The latter are often designed to alleviate accompanying symptoms, such as depression, restlessness, sleep disorders, and aggressive behaviour, or to improve cognitive function and retentiveness. Other non-drug approaches attempt to strengthen patients' competence in their daily activities and support caregiving relatives (hereinafter referred to as "caregivers"); for example, together with their caregivers or professional carers, people with Alzheimer's disease can learn to develop a daily routine.
No studies available for various treatment concepts
In order to determine the long-term benefit of non-drug interventions, IQWiG and its external experts searched for studies lasting at least 4 months: 33 studies including a total of 3800 patients with Alzheimer's disease were identified. The studies can be classified into 4 main treatment approaches: caregiver training, emotion-orientated interventions (validation and reminiscence therapy), cognitive training procedures, and activity-based interventions (physical and psychosocial activation). A number of further treatment concepts exist, but no studies on them are available.
None of the 33 studies compared a non-drug intervention with a drug intervention assessed by IQWiG (cholinesterase inhibitors, ginkgo compounds, memantine).
IQWiG categorized the reporting quality of 29 of the 33 studies as "poor". They are prone to bias and the data cannot be interpreted reliably. Overall, the long-term benefit of the treatment approaches investigated is thus not proven.
Caregiver training has been relatively well investigated
The evidence base on caregiver training is relatively good. As many as 17 of the 33 studies identified investigated this procedure. These studies also provided indications of a benefit, both with regard to accompanying symptoms, such as depression or agitated behaviour, and to the quality of life of caregivers. However, it remains unclear whether the statistically significant differences are large enough to be clinically relevant, i.e., relevant to affected persons in their daily life.
Caregiver training also seems to clearly delay nursing home placement of patients with dementia. However, this type of treatment may also cause harm: patients whose caregivers participated in a training programme were admitted to hospital or an emergency room more often than those whose caregivers did not.
Patients with Alzheimer's disease may also benefit from cognitive training procedures. IQWiG found indications that these procedures improve retentiveness in patients at an early stage of the disease.
IQWiG thinks that studies in the German health care setting are necessary
In view of these disappointingly unclear results, the Institute thinks that additional randomized controlled trials (RCTs) are absolutely necessary. These studies should contain multiple arms, i.e., should compare not only two, but several treatment alternatives. In IQWiG's opinion, only such a design would enable a direct and fair comparison of drug and non-drug treatment strategies. In addition, the studies should be conducted in Germany, as for some non-drug interventions, such as caregiver training, the national health care setting, i.e., the specific organization of health care, presumably plays an essential role.
The Institute Director Professor Peter T. Sawicki comments, "We have a growing medical and social problem; it is not to be expected that this problem will be solved with the help of drugs in the near future. Non-drug interventions are available that at least seem to have potential, but there are no studies that could prove this. It is not justifiable to make an exception for these interventions and use them widely without available proof of their effects, thus also accepting risks."
Methodological requirements for studies investigating non-drug interventions are high
According to IQWiG, the general problem of the benefit assessment of non-drug interventions is shown particularly clearly in Alzheimer's disease. These interventions are complex, and, for example, interaction between treating staff and patients may play a larger role than in drug interventions. The requirements for the planning and conduct of such studies are all the higher.
However, regarding study methodology, non-drug interventions lag far behind drug interventions. One important reason for this deficit is that, in contrast to the pharmaceutical sector, there are no authorities to press for the development of methods by means of the required approval studies. Unfortunately the IQWiG report on Alzheimer's disease once more confirms this well-known deficit. It was therefore hardly surprising to IQWiG that the methodological quality of studies in which the pharmaceutical industry was involved was relatively good.
Current promotion of research could help close gaps in knowledge
This addresses the next main problem: the funding possibilities for clinical research are in general clearly worse in the non-drug sector than in the pharmaceutical sector. Although there are, for example, manufacturers of medical technologies who could conduct studies, there is a lack of incentives and constraints in the form of patents and approval requirements.
Peter Sawicki states, "What is lacking in Germany is public research funding, independent of industry, for research questions relevant to the treatment of patients. This applies very specifically to non-drug treatment approaches. We must finally be allowed access to public financial sources for this type of research."
A step is being taken to solve this problem, at least in the case of Alzheimer's disease. At the end of 2007, the Federal Ministry of Health initiated a corresponding research promotion programme. In the area "Ensuring evidence-based health care", the Lighthouse Project Dementia also grants funding for the systematic evaluation of the latest scientific evidence. In particular, RCTs on non-drug interventions are being funded, which is the type of study design IQWiG considered in its benefit assessment.
Procedure of report production
The preliminary results (preliminary report) were published by IQWiG at the beginning of July 2008 and interested parties were invited to submit comments. Following the commenting procedure the preliminary report was revised and the final report sent to the contracting agency, the Federal Joint Committee, in mid-January 2009. The documentation of the written comments, as well as meeting minutes of the oral scientific debate, will be published in a separate document simultaneously with the final report.