Some completed studies are never published. An association between ‘significant’ results and publication has been documented across a number of studies, as summarized in Chapter 10 (Section 10.2). Finding out about unpublished studies, and including them in a systematic review when eligible and appropriate, is important for minimizing bias. There is no easy and reliable way to obtain information about studies that have been completed but never published. This situation is improving as a result of a number of initiatives:
The International Standard Randomised Controlled Trial Number Register scheme launched as the first online service that provided unique numbers to randomized controlled trials in all areas of health care and from all countries around the world and subsequently ClinicalTrials.gov (see Section 6.2.3.1);
The increasing acceptance on behalf of investigators of the importance of registering trials at inception;
The support of registration at inception by the leading medical journal publishers and their refusal to subsequently publish reports of trials not properly registered (De Angelis 2004, De Angelis 2005);
The US National Institutes for Health (NIH) Public Access Policy (see publicaccess.nih.gov/), which until December 2007 was voluntary but now requires that “all investigators funded by the NIH submit or have submitted for them to the National Library of Medicine's PubMed Central an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication to be made publicly available no later than 12 months after the official date of publication”.
Colleagues can be an important source of information about unpublished studies, and informal channels of communication can sometimes be the only means of identifying unpublished data. Formal letters of request for information can also be used to identify completed but unpublished studies. One way of doing this is to send a comprehensive list of relevant articles along with the inclusion criteria for the review to the first author of reports of included studies, asking if they know of any additional studies (published or unpublished) that might be relevant. It may also be desirable to send the same letter to other experts and pharmaceutical companies or others with an interest in the area. It should be borne in mind that asking researchers for information about completed but never published studies has not always been found to be fruitful (Hetherington 1989, Horton 1997) though some researchers have reported that this is an important method for retrieving studies for systematic reviews (Royle 2003, Greenhalgh 2005). Some organizations set up web sites for systematic review projects listing the studies identified to date and inviting submission of information on studies not already listed. It has also been suggested that legislation such as the Freedom of Information Acts in countries such as the UK and the US might be used to gain access to information about unpublished trials (Bennett 2003, MacLean 2003).
It is also important to identify ongoing studies, so that when a review is later updated these can be assessed for possible inclusion. Information about possibly relevant ongoing studies should be included in the review in the ‘Characteristics of ongoing studies’ table (see Chapter 4, Section 4.6.5). Awareness of the existence of a possibly relevant ongoing study might also affect decisions with respect to when to update a specific review. Unfortunately, no single, comprehensive, centralized register of ongoing trials exists (Manheimer 2002). Efforts have, however, been made by a number of organizations, including organizations representing the pharmaceutical industry and pharmaceutical companies themselves, to begin to provide central access to ongoing trials and in some cases trial results on completion, either on a national or international basis. In an effort to improve this situation, the World Health Organization (WHO) launched the International Clinical Trials Registry Platform Search Portal in May 2007 to search across a range of trials registers, similar to the initiative launched some years earlier by Current Controlled Trials with their so-called metaRegister. Currently (as at June 2008) the WHO portal only searches across three primary registers (the Australian and New Zealand Clinical Trials Registry, ClinicalTrials.gov and the Current Controlled Trials International Standard Randomised Controlled Trial Number Register) but it is anticipated that other registers will be included as the project progresses.