Possible explanations for inter-country variation
We received answers from researchers in all the ten countries and drug regulatory agencies in Finland, Norway and Sweden and from a Department of Health official in the UK.
There was nearly full consensus among our respondents that marketing by pharmaceutical companies is the main explanatory variable for prescribing choices, and particularly the driving force behind the prescribing of newer drugs, such as calcium channel blockers and angiotensin II receptor blockers.
There was some variation among the respondents regarding the policies, rules and regulations related to prescribing of antihypertensive drugs in the various countries, but few believed that this had a major impact on prescribing. The exceptions were the Finnish respondents, who believed that their national clinical guidelines program could have had an impact, and the UK Department of Health official who considered central guidance ("especially NICE guidance") a major factor.
The answers given to our question on why doctors prescribe older drugs was mixed. Some researchers pointed to price considerations (Denmark, Finland, Canada, US), and some made statements like "Some physicians prescribe according to evidence-based principles, but they are probably a minority" (Canada, France). There were several possible explanations for the differences in prescribing patterns between their own and the other countries:
...."it is MOST unusual for UK GPs to use combination preparations. It is regarded as poor practice." (British researcher)
"The very low usage of thiazides probably reflects the views of the prominent specialists and researchers in this field in Norway" ...... "Many of the experts are deeply involved in industry sponsored research and tend to favour new products and their own research." (Norwegian drug regulator)
"Denmark's relatively large share of thiazides may to some extent be explained by factors like domestic production"...."but may also reflect their better system for continuing drug education among their GPs (e.g. academic detailing). In Norway this education is almost entirely left to the pharmaceutical companies." (Norwegian researcher)
"Beta-blockers have a long tradition in Sweden." (Swedish researcher)
"I once asked an older cardiologist about the reason for this difference and the answer was that there was no major tradition for beta-blockers in Denmark" (Danish researcher)
"The most striking difference for Canada is the lack of combination use of thiazides with ACEI and ARBs. This is probably due to the fact that these combination drugs are not funded in many of the provinces. This leads to a seemingly greater use of thiazides and ACEIs alone." (Canadian researcher)
Seven of the eight drug company medical directors (including two alternates) agreed to be interviewed: four from Norway and three from the UK.
Differences in physicians' attitudes were thought by all the directors to partly explain the differences in prescribing between the UK and Norway; e.g. that British doctors generally are conservative and slow implementers of new interventions while Norwegian physicians are "early adopters":
"My perception is that we Norwegians are, in general, "early adopters" – we are attracted to the new and "hot", be it kitchen equipment or other things." (N2)
"UK is in general a conservative country when it comes to prescribing new drugs. New therapies are slowly taken up" (UK1)
"I think this [low use of combination drugs] reflects the general conservatism that is typical of the British." (N2)
"Could be that the British doctors are more conservative – it wouldn't be surprising knowing how conservative the British are, in general!" (N4)
"It is, perhaps, true that British doctors comply more with guidelines than their Norwegian colleagues. The British are perhaps more respectful towards authorities while the Norwegians are more individualistic in their attitudes." (N4)
"It may be true that Norwegian tend to disregard clinical guidelines and rather adhere to their own convictions. ......It is typically Norwegian that each individual has his own personal opinion." (N2)
"There is usually a slow uptake of newer drugs in the UK. New data typically doesn't impact immediately – unless they're very strong." (UK2)
"One new trial result is not enough for a UK-doctor – again a consequence of the conservatism we have." (UK3)
The Norwegian directors also believed that conducting trials in general practice has an impact on prescribing and that a substantially higher number of physicians involved in such trials in Norway could explain differences in prescribing patterns:
"Many trials are being run in Norway."..... "I believe that the hand-on experience doctors get from participating in the trials increases their awareness and influences practice." (N1)
"I do believe that running a study like this is, by itself, of value from the marketing perspective." (N2)
"Of course we conduct clinical trials with the aim of developing newer and better drugs, but a marketing effect is unavoidable, and is an added benefit for the company." (N2)
"Yes, involvement by doctors in the running of clinical trials probably has an impact. In Norway a much higher proportion of GPs participate in trials compared to, for instance, the UK." (N2)
"I don't think that is true [that the differences can be explained by the higher number of trials that are conducted in Norway]. I can only speak for our company, but we have run several trials in UK general practice – often in collaboration with sites in Norway and the other Scandinavian countries. So this does not fit with my understanding." (UK1)
"Norwegian physicians are in general rapid implementers of new therapies. A major explanation for this is probably the high number of large clinical trials that are run in Norway. Relative to our population the number of patients participating in clinical trials is about the double of what can be expected compared to other countries." (N3)
"Norway is a key area for clinical drug trials, e.g. studies of organoprotective effects of antihypertensive drugs. This has been driving prescribing to the right in the graph [i.e. towards the more expensive alternatives]. Recently we have seen a slight increase in the use of ARBs, for the treatment of migraine. Again, an example of high quality trial results being rapidly taken up in clinical practice." (N3)
"I don't think participating in trials will lead to a change in prescribing habit for a UK-doctor." ...... "We do [run clinical trials where GPs participate] ... but maybe we do it less than in Norway." (UK3)
British doctors were also believed to be more cost-aware, mainly due to local budgets which include drug expenditures, thus driving prescribing towards less costly alternatives:
"In the UK they have given budget-responsibility to the local GPs, which could limit spending on drugs, for instance." (N1)
"It's probably true that UK physicians are more cost-aware. One reason may be their tradition of local budgets. Actually, I think Norwegian doctors have become less cost-aware now than they were before. At least that's the impression I have from speaking to our representatives – they tell me that the doctors put very little emphasis on price." (N2)
"Cost considerations are also part of the picture. It is my impression that UK doctors are more cost sensitive. This has to do with the limited drug budgets for each practice, but I think UK doctors also are happy to prescribe thiazides and beta-blockers." (UK1)
"Maybe the British physicians are more cost-aware. I think Norwegian doctors have regarded the drug-reimbursement system as a bottomless pit. They may be concerned about the costs for their patients, but not the societal costs." (N4)
"I have mentioned drug formularies... Also, primary care trusts have budgets they are responsible for, which includes spending on drugs." (UK2)
"I don't think that UK GPs are particularly acquisition-cost aware, but the drugs that are included in their formularies have gone through a process of appraisal where cost-effectiveness is an important element." (UK2)
"It could be that in Norway you focus more on the patient in front of you. The UK-system is very cost-conscious." (UK3)
Local influence from pharmaceutical advisors was also mentioned as an important force that "pushes the use of thiazides – for pure cost reasons" (UK3). This "local guidance" was also seen as a reason why "UK-doctors are hard work for industry to influence" (UK3).
Views on the role of evidence among Norwegian and British physicians were contradictory. On the one hand the directors seemed to agree that there is a "bias for evidence-based medicine" (UK1) in the UK, but on the other hand the Norwegian directors claimed that physicians in Norway are very much focused on trial results and particularly hard endpoints, e.g. effects on mortality rates:
"Our impression is that the doctors in Norway put great emphasis on documentation – they look at the evidence. They want trials with hard end-points." (N1)
"I think there is a particular focus on large studies with survival endpoints among Norwegian doctors." (N2)
"I think Norwegian physicians are particularly interested in research and the results of clinical trials." (N2)
"I do have the impression that Norwegian physicians are focused on hard endpoints, but if there is any difference compared to British doctors I don't know." (N4)
"I think guidelines are important in explaining the UK prescribing pattern and there is a strong bias for evidence-based medicine. Thiazides and beta-blockers have been recommended as first line, and doctors have followed this recommendation." (UK1)
"UK doctors may be more difficult to persuade, perhaps, with their strong focus on evidence. They demand trials that have shown the effectiveness of drugs on hard end points – their clinical usefulness." (UK1)
"Also in the UK some physicians want hard end-points – especially the physicians in secondary care. Many GPs are more focused on controlling the blood pressure." (UK2)
"Maybe Norway is less evidence-based and more patient-focused? ..... There is a fundamental belief in endpoints and outcomes – there is a hang-up on this in the UK." (UK3)
The British directors agreed that the low use of combination drugs in the UK was due to therapeutic traditions largely seeded at medical school. One of them also believed that "the general push for generic prescribing plays a role, since the combinations usually are branded drugs" (UK3).
The high use of alpha-blockers in Norway was considered to be an artefact by some since current regulation only allows for the reimbursement of such drugs if they are used for hypertension, and not for benign prostate enlargement. However, one of the directors refuted this, citing a study conducted among general practitioners where only 5–10% of reimbursed prescriptions for alpha-blockers were made for individuals without hypertension.
Two Norwegian directors confirmed that the relationship between specialists and industry might be a factor:
"Conflicts of interest of opinion leaders may be an issue" ...... "Norway has a rather high number of opinion leaders in the cardiovascular area that have been active in collaboration with industry." (N2)
"Their engagement with industry is important for the services they provide to their patients, e.g. the chance of accessing new therapies, more intense follow-up of patients etc. This is less so in the UK. For this reason industry may find it more difficult to convince physicians in the UK with their arguments." (N3)
"To get opinion leader endorsement is important. They rarely go against established guidelines, so they generally support the use of thiazides. Also the opinion leaders put great importance on cost-effectiveness, while tolerability for instance is less emphasised. Regarding their links to industry I think they are cautious – they have their integrity to maintain." (UK3)
"One difference might by that Norwegian opinion leaders seem to be somewhat less keen on promoting a specific drug – they worry about their credibility." (N2)
"In fact, my guess is that marketing in general – also the use of opinion leaders – is more aggressive in the UK, if there is any difference at all." (N1)
One Norwegian director mentioned the role of patients: "In the UK I think the doctor-patient relationship is more traditional, with the physician deciding for the patient, while here the patients are more involved in decision-making; and when given the choice they prefer the 'latest model"' (N1).
Financial incentives were mentioned by one UK director: "In the UK there are local prescribing incentive schemes that reward generic prescribing, reward high use of drugs in accordance with guidelines, etc. The reward can be money, which goes to the clinic. The GPs are independent contractors – running their own business." (UK3)
One director suggested that a higher threshold for initiating treatment among Norwegian physicians means that a higher proportion of those who are treated need more than one drug, and that this influences the overall prescribing pattern.