Health care expenditure in the Netherlands increases each year, as it does in other European countries. Drug prescribing is an important contributor to this increase in costs, and these costs are expected to continue to increase relevantly in the coming years [1–3]. Medication is not always prescribed effectively: drugs may be prescribed unnecessarily and lower-cost alternatives are not always taken into consideration. The problem can be attributed to demographic factors (growth and ageing of the population), the trend towards new but usually more expensive drugs, patients' increased awareness, pressure from the industry, and last but not least the differences in prescribing practices between primary and secondary care oriented physicians [4, 5]. Physicians are also known to prescribe more easily as a result of today's high level of work-related stress and routines [6].

Clinical guidelines may induce small improvements, both in processes and in the outcomes of care [7]. Simple top-down dissemination of mono-disciplinary guidelines alone is not effective [8–12]. To bring about change, a more powerful strategy could be multidisciplinary guidelines and probably even more so if key regional representatives from primary and secondary care are involved in the development. Implementation experts indicate that multistage involvement in the development of a guideline can be a positive contributor to effective implementation of guidelines [13, 14]. If national guidelines are involved, adjusting them to the local situation and to specified needs experienced in the target group increases commitment [15, 16]. We have therefore adopted an intensive guideline development procedure, involving local representatives of the relevant medical disciplines [17, 18].

The intensity is related to the time and energy that was put into the strategy of guideline development to create support among GPs. We set up a study in which we assessed the effects of our intensive multistage guideline development. We hypothesised that this strategy could lead to a modest but relevant change of volumes of prescriptions in the desired direction. As we used two comparisons, we were able to study the effects of dissemination separately from the effects of involving the target group in the preparation and development of the guidelines.

As far as we can ascertain, the GPs in the two groups did not differ on the main characteristics. The mean age of male GPs in the intervention group was 50.0 years and 53.3 in the control group. The mean age of the female GPs in the intervention group was 48.8 years and 45.5 in the control group. Overall, the percentage of male GPs was only slightly different in both groups: in the intervention group, 85%(45) of the GPs were male, as compared with 76%(41) in the control group. Table 1 presents the mean total number of drug prescriptions per GP per year, standardised per 1000 enlisted patients over a baseline measurement (2001 or 2002), the short-term effects (one year) and long-term effects (two years). Table 1 also presents the absolute changes in the short term and long term per 1000 enlisted patients per GP. Table 2 presents the same data for the random sample of GPs who were invited for a more intense role in the development procedure.

Less than 10% of the GPs that were invited to play a greater role actually commented on the conceptual guidelines. The exact number varied according to the specific guideline. Most of the comments did not relate to content, but rather concerned questions about the development procedure.

For the guideline dissemination (quasi experiment), results show that a significant change in the desired direction was found for one specific antibiotic (mupirocin): a reduction of one prescription per 1000 patients compared to an increase of one (p = 0.0014) in the short term. No significant effect was seen for other antibiotics, either in the short term or the long term. For cholesterol, significant long-term effects were found; an increase of 112 prescriptions per 1000 patients in the intervention group compared to an increase of 54 in the control group (p < 0.0001). No significant effect was seen in the short term or long term for any asthma and COPD drugs.

For antibiotics and cholesterol, no additional effects were found in the randomised study of GPs with a greater involvement (table 2). For asthma and COPD drugs, significant changes were found in the control group instead of the intervention group. Instead of the desired increase, we found a decrease of 9 prescriptions per 1000 patients in the intervention group compared with a decrease of one prescription in the control group for inhaled corticosteroids for asthma (p = 0.0099).

We found no clear impact of disseminating the rigorously developed multidisciplinary guidelines on the prescribing performance of GPs. A significant effect was found for two drugs: mupirocin and cholesterol lowering drugs. The change in mupirocin however does not seem very relevant, because it is rarely prescribed and by and large prescribed for minor ailments. The long-term effect for cholesterol lowering drugs is interesting. The standard deviation of prescribing drugs per GP turned out to be unexpectedly large. Although no significant effects were seen for the other drugs, only small changes can be seen on other indicators. The invitation for GPs to be involved in the development procedure caused no desirable effects in the subgroup.

There are some issues for consideration. First, although unlikely the quasi-experimental design cannot guarantee that the observed changes are the result of the strategy. It is possible that the effects found were caused by coincidence or by an unknown non-specific factor. Although the intervention group in both designs seems to be higher in volumes of prescription at baseline, both groups seem comparable in the exposure to quality improvement strategies that have been performed otherwise in the region. A second issue for consideration is the pragmatic base of the trial in which two regions were compared. This has caused a restriction in the number of GPs in the trial. We were not in the position to improve this. Together with the relatively high variation among the primary variable (volumes of prescription per GP per 1000 patients per year) the power of the study was negatively influenced. Another power calculation executed after ending the study, based on the large standard deviations and the number of GPs, showed that this resulted in a power of 40%. In this study only large differences could be detected. We found a few significant results, although the significant effect of mupirocin is not so interesting because mupirocin is rarely prescribed and the disease is a minor ailment. Given the fact that this study was no selected sample and the participating GPs were a fine representation for the Dutch GPs other results are not expected in larger trials. Besides, when evaluating this intervention in an economic study we wonder if the changes in prescribing behaviour are in balance to such huge efforts made in investment and implementation costs.

Only volume data of prescriptions were used in this initial stage of the study. These figures are therefore not linked to any diagnosis. However, some drugs are prescribed for several different medical problems, while the guideline may contain opposing prescription recommendations. For example, amoxicillin is recommended for the treatment of bronchitis and otitis media acuta, whereas amoxicillin is discouraged in cases of acute cystitis. On the one hand, for statin use, there is a situation of overuse for patients with low risk on cardiovascular disease; on the other hand, there is a situation of underuse for high-risk patients like diabetes patients [21]. It is therefore possible that the results are somewhat underestimated in the sense that possible results were kept hidden. Additional information about diagnosis and cholesterol rates would be needed to make a more precise analysis.

A strong aspect of our study is that long-term effects were measured. For statin-prescription, the initial non-significant effect appeared to be significant at the long run. A positive factor that may have contributed to an increased willingness to follow the cholesterol medication guideline is that our strategy concerns guidelines that have been formulated by representatives from all disciplines and was intended to improve prescription behaviour in both primary care physicians ánd medical specialists.

Overall, the implementation strategy only generated limited results. Implementation experts indicate that if guidelines are developed by the clinicians who are to use them this will be a positive contributor to the effect of guidelines. Achieving consensus on draft guidelines and creating a sense of 'ownership' through a process of development on several levels (central, local and individual) is essential for successful implementation of guidelines [22, 23]. We have paid specific attention to this aspect, firstly by involving representatives from all disciplines in the development of the guidelines. The term intensity is therefore related to the time and energy that was put into the guideline development strategy to create support among GPs. Secondly, we also focused specifically on the doctors' acceptance of the guidelines by including them in the validation procedure. It is not clear why the GPs did not respond to the invitation for comment. Possibly, we were successful in choosing opinion leaders to such extent that GPs did not see the need to comment on guidelines that were prepared by GPs they trusted. A second explanation lies in the assumption that the invitation by mail did not work: only a few GPs responded to the invitation to comment on the guideline. GPs might have had comments but did not think this would have any impact in the final guideline. In short, we did not succeed in getting GPs involved locally in the validation procedure. Apparently this way of getting GPs involved is not appropriate and possibly explains why the effect was only limited.

To create involvement in the validation procedure we searched for a successful method to achieve this. During the validation of the antibiotics guideline we started with visiting PTAMs in the region to get comments on the conceptual guidelines and create involvement. This turned out to be very time consuming and caused much delay in the dissemination of the final guideline. Therefore, during the validation of the asthma and the COPD guideline we chose for a less labour-intensive method by asking GPs to comment by mail. After finishing the analyses for this study, we subsequently started (not included in the data of the manuscript) with inviting GPs to feedback meetings. The results of this method were more convincing. We highly recommend the feedback meetings to be an effective method to create involvement among GPs during the validation procedure.

To obtain a more solid or extensive effect, an additional implementation strategy is desired. Feedback and reminders could be an necessary strategy to change GPs behaviour [24–26]. For example, a computerised decision support system could give feedback to a doctor as soon as the prescription behaviour differs from the behaviour recommended in the guideline. As long as the doctor does not deviate from the guideline, the system will not interfere with the primary care physicians' information system, and the doctor giving the prescription will not be interrupted by the feedback system.

We did not perform an economic evaluation by relating the (change in) costs of prescription to the costs of the interventions (guideline development and dissemination) [27, 28]. If we were to choose to compare the total expenses of the intensive development procedure of all guidelines with the cost savings, we would expect all the findings to be negative, because the strategy was time and energy consuming and its impact was only moderate. Before aiming to intensify the development procedure of guidelines, the costs and savings of such a strategy need to be investigated thoroughly and executed when the proceeds of the intervention outweighs the costs of it [29, 30].

Disseminating multidisciplinary guidelines that were developed within a region, has no clear effect on prescribing behaviour even though GPs and specialists were involved more intensively in their development. Apparently, more effort is needed to bring about change.