After a hectic period, in which the Geneesmiddelenbulletin’s right to exist and even its independence were challenged (not for the first time), the journal has now entered a calmer period, partly thanks to the transition to Domus Medica in Utrecht, the technical collaboration with the Medisch Contact journal and the financial guarantee by the Dutch Ministry of Health, Welfare and Sport (VWS). Now that the journal is starting a new period in its existence, we would once again like to outline how the Geneesmiddelenbulletin works (Gebu 2010; 44: 25-29).
The Geneesmiddelenbulletin Foundation publishes a monthly bulletin intended for anyone involved in prescribing and providing medicines. Its purpose is to promote a more rational approach to pharmacotherapy, its primary focus being its usefulness for day-to-day practice, for the local pharmacotherapy discussion groups of general practitioners and pharmacists and for pharmacotherapy teaching at universities. Its feature articles and discussions of new products in particular strive to provide as comprehensive a picture as possible of all the relevant research so that readers, unimpeded by bias, can draw their own conclusions. The Geneesmiddelenbulletin (Gebu) uses these articles as the basis for an evidence-based approach to medicine, as this adds to the value of the information it presents.
Information on pharmaceutical products comes primarily from the industry. The pharmaceutical industry in the Netherlands has reported spending about 10% of its budget on marketing, including advertising, brochures and mailings.1 A further 12.5% of the budget goes to the provision of scientific information and services, through medical representatives, scientific publications, conferences, teaching materials and continuing education courses.1 It is the aim of independent information sources, such as the Farmacotherapeutisch Kompas (national formulary) and theGeneesmiddelenbulletin, to provide some objective and impartial information, even though it can only spend a fraction of the money laid out by the commercial sector.
It is against this backdrop of openness and verifiability that this article explains the way in which the Geneesmiddelenbulletin works. This is particularly important now that the bulletin is once again going to continue in the form of an independent foundation, and it is these recent developments that induced us to explain once more its approach, which has not changed. After a short survey of the history of the Geneesmiddelenbulletin, its aims and basic principles are dealt with. Subsequently we introduce the people involved in the production of the journal, and finally we explain the procedures an article undergoes before it appears in print.
The Geneesmiddelenbulletin was first published in 1967 under the auspices of the Directorate of Public Health at the former Ministry of Social Affairs and Public Health. At that time the dynamic developments in the field of pharmacotherapy and the lack of objective sources of information suggested there was a need among prescribers for independent information on medicines. The American Medical Letter on Drugs and Therapeutics (1959) and the British Drug and Therapeutics Bulletin (1962) were used as models for the new journal.2 Originally the Geneesmiddelenbulletin contained many articles translated from these English-language sister bulletins, but demand grew for articles more particularly relevant to the situation in the Netherlands. Recommendations for the use of antibiotics in the United States, for example, are not automatically applicable in the Netherlands.
In 1988 the Geneesmiddelenbulletin was for some time under threat of closure. This was not due to any criticism of the quality of the bulletin, but rather a consequence of cost-cutting operations by the government. Consorted action by many of those involved with the bulletin prevented its demise. The bulletin was privatised in 1990, and published by the independent Geneesmiddelenbulletin Foundation, and as Gebu 1999; 33: 1-4 reported: ‘Its continued existence is nowadays fully secured’.
Nevertheless, the existence of the Geneesmiddelenbulletin came once more under threat in 2003, when the then Minister of Health, Welfare and Sport announced the intention to reduce its subsidy by 90%. Massive support from doctors and pharmacists in the form of numerous e-mails, faxes, and letters managed to convince the Minister that this would have highly undesirable consequences. In the end, the journal’s subsidy was cut by only 10%, under the condition that the journal would be accommodated within a larger organisation, the National Health Insurance Council (CVZ). The expected advantages of the cooperation with CVZ have, however, failed to materialise since then. In particular, it turned out to be difficult to combine the journal’s editorial independence with the CVZ’s desire for control over all statements made under its responsibility. This problem was brought to a head when court cases were initiated by pharmaceutical companies. The two parties then amicably decided to end their collaboration, and the Geneesmiddelenbulletin was transferred to Domus Medica in Utrecht, where it started a technical collaboration with the Medisch Contact journal. Since then, a new Geneesmiddelenbulletin Foundation has been founded. During the transitional period, in 2009, the Ministry made an attempt to limit the journal’s objectives to that of a newsletter on treatment guidelines. This suggestion also met with fierce resistance, however, and the Dutch Parliament voted against the plan, so this third threat to the identity and continued existence of the Geneesmiddelenbulletin was also averted. The Minister recently told Parliament that the Ministry would continue to be the journal’s main sponsor.
Aims and Basic Principles
Objectives and structure. The objective of the Geneesmiddelenbulletin Foundation is to promote rational pharmacotherapy, which may be regarded as the practical application of the principles of ‘evidence-based medicine’. Rational pharmacotherapy can be defined as prescribing the right medication to individual patients or populations, at the time when it is needed, using a dosage scheme that corresponds to the most suitable profile in terms of efficacy, side-effects and costs. The Geneesmiddelenbulletin tries to achieve this aim by providing independent and objective information about drugs to all those involved in prescribing and providing them.
The Foundation has a board of governors, an editorial committee, an editorial office and an advisory board, each with their own part to play. The board of governors principally concerns itself with financial, organisational and personnel matters. The chief editor is the chairperson and also a member of the editorialcommittee, and is responsible for the content of the journal. The editorialcommittee consists of a minimum of five members, including general practitioners, pharmacists (both hospital- and community-based) and medical specialists. They are members in a private capacity and do not represent any organisations. They meet on a monthly basis to discuss the ongoing publications, the choice of articles and the editorial policy. The editorialcommittee shares the responsibility for the articles and the assessments of the place of a drug in the pharmacotherapeutic repertory. It is supported by an advisory board, which meets with the editorialcommittee twice a year and consists of a minimum of 10 and a maximum of 20 persons, including prescribing specialists, pharmacists, general practitioners and methodologists. They too are members in a private capacity and do not represent any organisations. The advisory board offers advice on the contents of the journal, the editorial policy and the choice of articles, and also offers critical comments on each article. The preparatory and actual editorial work takes place in the editorial office, staffed by the chief editor, a scientific editor and a copy editor and/or editorial assistant.
Independence. Maintaining the independence of the information involves various aspects. The Geneesmiddelenbulletin wishes to protect its contents from any influence by the pharmaceutical industry or even any semblance of such influence. In order to guarantee its independence, the bulletin is not financed by profit from advertising. This leaves the editors free to comment critically on issues such as new drugs, side-effects and promotional activities. The same holds true, however, for its independence from government-related institutions such as the Medicines Evaluation Board (CBG, the Dutch registration authority), the Health Inspectorate (IGZ), the directorate for the provision of medicines of the Ministry of Health, Welfare and Sport, and the National Health Insurance Council (CVZ), as well as professional and patient groups. There is no question of any of these groups having any influence on its contents.
Sources of income. The subsidy provided by the Ministry of Health, Welfare and Sport is currently the most important source of income. It enables the bulletin to be distributed, free of charge, to all doctors, pharmacists and dentists who are members of their professional organisations. To save on postal charges, the Geneesmiddelenbulletin is distributed along with the three journals of these professional organisations. Those who do not receive these journals can take out a subscription. This group makes up by far the largest share of the 400 paying subscribers, who represent an additional, though limited, source of income. Students of medicine and pharmacy in the final stages of their studies receive the Geneesmiddelenbulletin free of charge. This brings the total circulation to more than 58 000 copies.
ISDB. The Geneesmiddelenbulletin is an active participant in the International Society of Drug Bulletins (ISDB). This organisation unites more than sixty independent drug bulletins world-wide, some major examples of which are listed in the figure below.3 One of ISDB’s activities is to discuss with the European registration authorities measures to promote transparency concerning the registration procedures for new drugs.4 The Society also contacts members of the European Parliament and supplies them with information about matters such as ‘direct-to-consumer advertising’(DTCA). The members of the ISDB also actively exchange articles, discuss editorial procedures and promote their shared interests.
Consumer’s Association. There are regular meetings with the Dutch Consumer’s Association (Consumentenbond) at which the contents of planned articles are discussed, with a view to re-printing brief summaries of articles that are of interest to the Consumer’s Association in their health magazine.
Figure. International Society of Drug Bulletins (ISDB) and some of its major bulletins.
The feature article. Traditionally, the feature article (currently the ‘blue section’ of the journal) is the mainstay of the Geneesmiddelenbulletin. It usually deals with the treatment of a specific clinical condition, such as heart failure or vaginal infection. A review may also be prompted by the arrival of a new group of drugs, at the time when a second representative of such a group comes onto the market. A third category of feature articles is that devoted to specific problems which can arise in the prescribing of drugs, like the development of resistance, side-effects and interactions. The diversity of the readership, and Geneesmiddelenbulletin’s aim to cover all aspects of developments in drugs, result in a huge variety of topics, which may include highly specialised drugs. In addition, the journal may include articles expressing opinions of the editorial committee and advisory board.
Bulletin Board. The Bulletin Board section (the yellow section of the journal), was introduced in 1991, with the specific aim to provide the most up-to-date information. The Nieuwe geneesmiddelen (new drugs) part discusses essentially all recently introduced drugs that contain a new active ingredient, with the exception of extremely specialised drugs aimed at a small patient group. We aim to review a drug as soon as possible after it has become generally available on prescription and is reimbursed by health insurers, and to provide clear information indicating its place in the existing pharmacotherapeutic repertory. The key to this procedure is the comparison between the new drug and an existing standard therapy in terms of the balance between efficacy and side-effects. An important source for this kind of information is formed by the pharmacotherapeutic reports by the CVZ’s committee for pharmaceutical assistance (CFH). The comparison can of course only be a provisional one, as good comparative studies are initially often unavailable. Moreover, as the drug becomes more widely used, more side-effects, contra-indications and interactions may come to light, which were not revealed by clinical trials involving mostly only small groups of selected patients. Some recent examples of drugs taken off the market for this reason are rofecoxib and valdecoxib.
The Bulletin Board also presents other regular items. Variaties (variations) looks at interesting new indications for the use or administration of existing drugs. Under the heading Let op! (watch out!), the Bulletin Board reports on new findings regarding side-effects, contra-indications and interactions. The Bulletin Board also devotes space to book reviews, dissertations and reports. Developments in the local pharmacotherapy discussion groups and news about drug registrations, the reimbursement system, drug costs and promotional activities all regularly make an appearance. A ‘website of the month’ feature was recently added.
Preparations. The editorial committee formulates its editorial policy in consultation with the advisory board, and decides which subjects are to be dealt with and when. The feature articles are usually written by external authors at the request of the editorialcommittee. In the interest of impartiality we endeavour to opt for authors who have no ties with any particular pharmaceutical company. The potential author may ask to be sent articles on the randomised, double-blind controlled trials published on the subject in question. Reports on these trials are obtained by the editorial office by systematic search operations using the Medline and Embase search engines and the Cochrane library. Information is also obtained from ISDB sister bulletins, review articles and text books.
How the feature article is developed. The first draft received from the author(s) is checked on its content and adapted to the house-style by the staff at the editorial office. In practice, this may mean that the structure is adjusted if necessary. Some parts of the text may be condensed (e.g. pathophysiology) and others may need to be added (e.g. interactions). The editors also look for uniform usage of medical terminology and literature listings, using the Vancouver rules.
The draft version of the article thus created is then sent to the editorial committee, to the advisory board and to a minimum of five experts in the field (external reviewers) for peer review. A number of permanent reviewers are also asked for their views. These include representatives of the Farmacotherapeutisch Kompas, the Dutch scientific associations of general practitioners and pharmacists, as well as professional specialist associations. This system ensures that every article is reviewed by an average of 30 to 40 experts. The companies that manufacture the products are also given an opportunity to comment on the article. The name of the author is not printed on the draft article, in order to ensure an objective judgement by the experts.
Staff at the editorial office collect and consider the comments made by the reviewers and then perform a further literature search. A proposal for processing the comments made by the reviewers is formulated and laid before the editorialcommittee. At its monthly meetings, thecommittee decides which suggestions to submit to the author. The summarised and blinded comments and text suggestions are then discussed with the author, usually in person.
The resulting second draft of the article is returned to all of the above reviewers and drug companies, accompanied by an explanation of the revisions. They have another chance to review and comment, should they wish to do so. After being evaluated by the editorial office, such comments are also sent to the author, while at the same time the final textual corrections are made. It is only then, usually about six months after the delivery of the first draft, that the article is considered ready for publication. Sometimes, even more time is necessary. This is an inherently laborious process, as it involves the opinions and arguments of many experts who all have the right to hear and be heard. The feature articles are meant to offer guidance for a number of years.
Bulletin Board. Unlike the editorial process for the feature article, the Bulletin Board (Prikbord) is written by a number of regular authors, including staff at the editorial office, in close cooperation with the Farmacotherapeutisch Kompas, the Netherlands Pharmacovigilance Centre (Lareb), the CBG and the scientific institute of pharmacists (WINap). Another difference is that the texts concerning new drugs, variations of usage and side-effects are sent to the external reviewers and drug companies for review only once. This results in shorter production times and enables the Bulletin Board section to provide more recent information. The Bulletin Board articles are also initially sent without the name of the author.
Sources of Literature. The Geneesmiddelenbulletin uses guidelines published by the Dutch College of General Practitioners (NGH- standaards) and consensus texts as its literature sources, provided of course that these are available for the subject in question. Such a consensus of opinion is, however, not always arrived at independently of the pharmaceutical companies, and NHG guidelines may sometimes be in need of revision. Hence, the Geneesmiddelenbulletin always tries to draw independent conclusions. To this end the bulletin uses only information derived from well-designed and competently performed and reported trials, whose results are published in journals that practise a system of peer review. The Geneesmiddelenbulletin subscribes to the ‘Consolidation of the standards of reporting trials’ (CONSORT) guidelines on reporting about randomised clinical trials and hence about the efficacy of medicines (Gebu 2009; 43: 111-113) and actively checks articles against these guidelines.5-7 As regards reporting about observational studies, particularly research into side-effects of drugs (cohort studies, case-control studies and cross-sectional studies) the Geneesmiddelenbulletin subscribes to the ‘Strengthening the Reporting of OBservational Studies in Epidemiology’ (STROBE) guidelines.8-10 In principle, the Geneesmiddelenbulletin does not publish results derived from abstracts, posters, papers read at conferences, data on file and expert reports, as this material has usually not been verified by independent reviewers. It has happened more than once that an abstract subsequently submitted as an article failed to pass a journal’s editorial review, or presented different data. Moreover, in many cases the information provided is insufficient for an adequate interpretation of results. With the exception of some very rare breakthroughs, it is difficult to imagine why a doctor would want to prescribe a drug which has no back-up in the pharmacotherapeutic literature. Only in cases where there is no source of reliable, published information whatsoever, and it is nevertheless essential to indicate a product’s place in the pharmaceutical repertory, will the Geneesmiddelenbulletin use incompletely verified information. This is always pointed out explicitly in the article.
Letters to the editor. Letters from readers in response to articles are always answered personally, but are not placed in the paper edition of the bulletin. Most of the letters concern matters which have already been discussed by the wide range of experts and where necessary incorporated in the text during the elaborate review process prior to publishing. It is quite possible, nevertheless, that minor discrepancies may occur in the interpretation of research findings, and any mistakes will naturally always be rectified, or supplementary information may be published. Sometimes letters may occasion a follow-up article. Since 2011 letters can be published on the website if the editorial committee approves that.
Procedure for rectifications. The Geneesmiddelenbulletin Foundation is an impartial organisation, independent of third parties such as the pharmaceutical industry, government departments, professional organisations and patient groups. Articles are only published after extensive consultation with a range of experts. With very few exceptions, the conclusions are based on published and therefore verifiable results of randomised, preferably double-blind, clinical trials with appropriate control groups. If, despite this very careful procedure, someone considers that any part of an article is in error, they can report this error to the editorial office by letter or e-mail. The editorial staff will then consult with the original author(s) and experts to consider the comment and, if necessary, will draft a rectification statement. This statement will be published in a subsequent issue of the Geneesmiddelenbulletin. The error will also be corrected at once in the journal’s web edition.
The place of a newly developed drug within the existing pharmacotherapeutic repertory is determined by the balance between its efficacy and side-effects in comparison with that of the standard therapy, and there may well be differences of opinion about this place. The editorialcommittee will answer any written comments submitted to it, but as stated above, the Geneesmiddelenbulletin does not publish letters to the editor. In addition, many articles are submitted for inspection to the relevant pharmaceutical company before publication, so that any debate about the place of the new drug in the repertory will already have been concluded at an earlier stage of the procedure. Nevertheless, it may happen that articles are substantially altered after consultation with experts and industry representatives. In any case, however, the stakeholders will have been given the opportunity to advance their opinion and to comment on the draft text and suggest adjustments.
Articles published on the Geneesmiddelenbulletin website are not altered when new information becomes available, for instance in the form of new research findings. If such findings affect the place of a drug within the repertory, the editorialcommittee can publish new information on the subject at a suitable date, usually in the form of a Bulletin Board article under the heading of Opnieuw Bezien (Reassessment).
Looking to the future
Our own website came online in 2010, via the Artsennet site. This offers not only the complete monthly bulletin in electronic form, but also the entire collection of articles published in recent years. The use of Google ensures that articles can be easily retrieved. We also intend to offer summaries of articles in English.
Summary and conclusion
The Geneesmiddelenbulletin Foundation is an impartial organisation, independent of third parties such as the pharmaceutical industry, government departments, professional organisations and patient groups. Articles are only published after extensive consultation with a range of experts. With very few exceptions, the conclusions are based on published and therefore verifiable results of randomised, preferably double-blind, clinical trials with appropriate control groups. The essence of the discussion of new drugs is to determine their place in the pharmacotherapeutic repertory, which is done by systematically evaluating the balance between efficacy and side-effects, compared to the standard therapy.
Key words: operating procedure, Geneesmiddelenbulletin, feature articles, bulletin board, editorial procedure, rectification procedure
- Jong-van den Berg LTW de, Buurma H. Communicatie. In: Buurma H, Beudeker HJ, Jong-van den Berg LTW de, Leufkens HGM (red.). Het geneesmiddel. Maarssen: Elsevier Gezondheidszorg, 2005: 188-211.
- How Drug and Therapeutics Bulletin produces articles. DTB 1997; 35: 73-74.
- Hoen E ’t. ISDB: dedicated to ensuring reliable drug information. WHO Essential Drugs Monitor 1997; 24: 11.
- Abbasi K, Herxheimer A. The European Medicines Evaluation Agency: open to criticism, transparency must be coupled with greater rigour. BMJ 1998; 317: 898-900.
- Verslaglegging van gerandomiseerd medisch-wetenschappelijk onderzoek volgens een standaardmethode; de ‘Consolidation of the standards of reporting trials’ (CONSORT) [redactionele kanttekeningen]. Ned Tijdschr Geneeskd 1998; 142: 1089-1091.
- Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA 1996; 276: 637-639.
- CONSORT Group. The CONSORT statement (2001). [document op het internet, geraadpleegd 16 november 2009] URL: http://www.consort-statement.org/consort-statement/overview/.
- Elm E von, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The strenghtening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007; 147: 573-577. Of via URL: http://www.strobe-statement.org/index.php?id=strobe-publications.
- Vandenbroucke JP, Elm E von, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al. Strenghtening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration. PLoS Med 2007; 4: 1628-1654. Of via URL: http://www.strobe-statement.org/index.php?id=strobe-publications.
- Stehouwer CDA. Rapportage van observationeel onderzoek: nuttige en welkome aanbevelingen ter verbetering [commentaar]. Ned Tijdschr Geneeskd 2008; 152: 182-184.