Quality control

Publication planning in emerging markets is becoming an increasingly important field of discussion, as was demonstrated at the recent International Society for Medical Publication Professionals' (ISMPP) Annual Meeting in the US. The gathering attracted over 425 delegates, including approximately 350 from the US and 60 from Europe and just a few from other regions, but despite this an entire session was dedicated to this topic.

As the meeting highlighted, the shift of trials into emerging locations has been ongoing for some time, with the aim of accelerating clinical development programmes.  It is a trend that is set to continue. Compared with 2006-2008, in 2008-2010 there was an increased focus on North Asia (+ 1.2 per cent sites) and East Europe (+ 0.4 per cent) and a decrease in established regions including Europe and North America (- 1.1 per cent) and Latin America (- 0.4 per cent). In addition, emerging markets are predicted to contribute 90 per cent of the growth of the pharmaceutical industry over the next 10 years.

Chinese publications increase
The growth in research efforts in emerging markets has been mirrored by growth in biomedical publications. Based on data from the life sciences archive resource, PubMed, the number of articles published annually between 2000 and 2009 grew 67 per cent. However, the growth was not equal across all regions; cumulatively, the proportion of articles from China, South Korea, Brazil, India, Turkey, Taiwan and Iran increased 9 per cent. Up from ninth in 2000, China is now the second most prevalent producer of biomedical research publications, generating 6.7 per cent of the biomedical literature, compared to the US with 28.2 per cent (first position), the UK with 6.3 per cent (third) and Japan with 5.8 per cent (fourth). Notably, the US, UK and Japan saw a combined 6.6 per cent decrease in biomedical publications over that same time period.

English remains the 'lingua franca' of the biomedical literature. However, the 'publish-or-perish' mantra seems even louder in the emerging markets. English-language 'international' journals generally have much higher impact factors than those published nationally in local languages. In China, scientists can be pushed towards these English-language journals, not just for the prestige, but also because there is a financial incentive. The more prestigious the journal, the larger the reward, according to the April 2011 issue of Learned Publishing. In addition to issues relating to quality, as will be discussed below, this also hinders the ongoing development of Chinese journals.

The traditional research regions, the US and Europe, have raised concerns regarding both the quality of the data from emerging regions and the representativeness of the results. However, publication planners are not just concerned about the data, but also about its publication.

Irrespective of region, publication of clinical data in the peer-reviewed literature remains an expectation of the medical community. The expectation is also that those responsible for the data, its analysis and reporting are accountable for the publication, via appropriate authorship, and that that the contribution of any individuals involved in the publication, but not eligible for full authorship, will be acknowledged. US and EU legislation requires the public disclosure of clinical trial data in standardised databases. The US is ahead of the EU in this regard, as this already happens via its National Institutes of Health website, while the European clinical trials database, currently summarises study design only. However, there is no legislation that mandates publication of study results.

Selective publication
There have been examples of companies with unpublished clinical studies and 'ghost-written articles' reported recently. Although they have come to light not long ago, unpublished studies tend to be those conducted and completed some years previously and can contain data on drugs regularly being prescribed today. The practice of 'selective publication', concerned with ensuring maximum publication of positive data, but limited or no publication of inconclusive or negative data, has been the subject of a number of high-profile media reports. Sceptics have gone so far as to suggest that companies which do not publish all of their clinical research should be prevented from conducting it. This scandal of unpublished data is set to run on.

Latterly, different organisations have made efforts to underline the importance of publishing clinical trial data in addition to posting results in clinical trial databases. Most recently, a joint position from the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), the European Federation of Pharmaceutical Industries and Associations (EFPIA), Japan Pharmaceutical Manufacturers Association (JPMA) and Pharmaceutical Research and Manufacturers of America (PhRMA) on the 'Publication of Clinical Trial Results in Scientific Literature' specifically stated that: 'All industry-sponsored clinical trials should be considered for publication in the scientific literature irrespective of whether the results of the sponsors' medicine(s) are positive or negative.' The statement added that all phase III clinical trials and any clinical trial results of significant medical importance should be submitted for publication, including investigational clinical products for which development programmes were discontinued.

The ISMPP-developed Good Publication Practice 2 guidelines (GPP2) pre-date the most recent industry guidelines, but in 2009, updating the 'Good publication practice for communicating company sponsored medical research' from 2003, they recommended that sponsors worked with investigators, authors and contributors to report and publish studies in a timely and responsible manner. GPP2 also reiterated that ghost-writing was unacceptable and that authorship of industry-sponsored research should follow the widely accepted criteria set out by the International Committee of Medical Journal Editors (ICMJE).  Annually updated, the ICMJE's 'Uniform Requirements for Manuscripts Submitted to Biomedical Journals' does not allow for either 'ghost-authors' or 'honorary/guest-authors'.

Quality worries
The concern from publication planners is that sponsors and authors from emerging markets may not be as sensitised as those in western Europe and the US to the issues around publication practices. Without an awareness of what is required, it would be nearly impossible for these regions to adhere consistently to the high standards that have become the norm in Europe and North America.

For example, as reported in Nature in 2010, the Chinese government has acknowledged a 'severe' problem with China's scientific publishing and a 'big gap between quality and quantity'. Plagiarism is considered one of the main types of scientific misconduct, but is apparently commonplace in some Chinese journals. The problem is so acute that the government has introduced legislation to tackle the worst offenders.

Publication planners are also concerned about authorship. In some countries, especially in Asia, it is acceptable for the head of the department to be included as an author as a mark of respect, irrespective of whether or not he or she qualifies as an author according to the recognised International criteria. Whether or not such concerns are well founded, they are understandable given publication 'misconduct' reported in the media, which has caused such a trust issue between pharma and the medical community.

There are many publication planners in Europe with a global remit. For some, the responsibility extends only as far as to ensure English-language publication of 'global' (ie, international) studies. For others, the task is more complex and some have responsibility for all publications on a particular product where the company is involved in sponsoring the research, irrespective of where the research was conducted or where it will be published.  

Ethical standards
To the outside world, if data publication does not conform to ethical standards, it does not matter where industry-sponsored research is conducted or which region was responsible for its publication. In addition, online publication and internet translation services mean that there really is no such thing as a 'local publication' in today's world. Companies should have a global publication policy that applies to all company employees around the world. This policy should cover all aspects relating to publications, but should confirm specifically that: companies will endeavour to publish the results of all of their studies conducted in patients (thus avoiding publication bias); all authors will meet ICMJE authorship criteria (avoiding guest/honorary authorship); conflicts of interest will be disclosed and that any professional medical writing support will be fully and specifically acknowledged (eliminating ghost-writing). This policy needs to be supplemented by regular training of company staff and an auditable mechanism, such as documentation, that confirms that the policy has been adhered to for each study and publication.

Transparent, complete and comprehensive publication of clinical trial data is an essential component in the rebuilding of pharma's reputation. Ensuring this happens in every region is paramount.

The Authors
Sarah L Feeney is head of scientific direction at Complete Medical Communications and European-At-Large Trustee of ISMPP.

Russell Traynor is strategic business unit head at UBC-Envision Group and President-Elect of ISMPP. The views expressed in this article are those of the authors and do not necessarily reflect the official views of ISMPP, Complete Medical Communications or UBC-Envision Group.

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