Karen King, PhD, ISMPP CMPPTM, Jason Gardner, PhD, ISMPP CMPPTM, Complete Medical Communications,
a McCann Health Company, UK
In the evolving landscape of medical publications, the question of whether to release study data as soon as they are available or to plan release based on a “story flow” is front-and-center. Recent regulation changes on the release of clinical trial results are an important consideration and will likely continue to have an impact on publication planning.
Historically, when generating a publication plan, a thorough strategic analysis of the therapeutic and competitive landscape was instrumental in deciding the “story” that would be told and the timing with which to publish data. Would all publications be held until just before launch, or would certain data perhaps be held back with a plan to publish to coincide with a competitor’s launch? Scene-setting reviews to set the stage for the “story” were also commonplace.
However, over the past few years, there has been a definite move towards planning publications purely based on when data are available. This trend started with the US Food and Drug Administration (FDA) Amendments Act (FDAAA) of 2007, which required FDA-regulated drug, biologic, and device product clinical trials (except Phase 1) to be registered on the ClinicalTrials.gov website (ie, study information and summary results), run by the US National Library of Medicine at the National Institutes of Health (NIH).1 Simultaneously, there had also been growing public opinion that publication practices were sub-optimal, with a need for greater transparency and additional ethical publication practices.
Furthermore, updated Good Publication Practice guidelines (GPP3), sponsored by the International Society for Medical Publication Professionals (ISMPP) and published in 2015, also emphasized the importance of reporting clinical trial results in a timely fashion.2 Although international regulations differ, GPP3 specifically recommends the submission of manuscripts within 12 months of study completion for licensed products, of product approval for investigational products, and of the decision to withdraw for discontinued products.3 This is aligned with the European Federation of Pharmaceutical Industries and Associations/International Federation of Pharmaceutical Manufacturers and Associations/Pharmaceutical Research and Manufacturers of America/Japan Pharmaceutical Manufacturers Association (EFPIA/IFPMA/PhRMA/JPMA) joint position statement.3
According to GPP3, the role of publication planning is to support research sponsors, authors, and steering committees (if they exist) with communicating results from clinical trials in a responsible, ethical, complete, and timely manner (Figure 1 below).2,4
New Public Disclosure Laws
The NIH Final Rule, released in September 2016, made the FDAAA 2007 recommendations mandatory. As of January 18, 2017, the responsible party is required to submit the results of applicable clinical trials5 on all drug, biologic, or device products, whether they are FDA-approved or not, no later than 12 months after the primary completion date (PCD),6 with commencement of results posting from April 2018. Delayed posting of up to two additional years is possible if the sponsor certifies that it intends to continue development of the drug, biologic, or device product for initial approval by the FDA.6
The European Medicines Agency (EMA) Clinical Data Publication Policy (0070) requires that for all centrally authorized products, the clinical data overview (clinical overview, clinical summaries, and clinical study reports) will be published from October 2016.7 Moreover, the EMA Clinical Trial Regulation EU No. 536 will result in all clinical trial-related information (including summary of trial results and a lay summary) of investigational medicinal products, regardless of whether they have a marketing authorization, being posted on a future EU portal and database.8 This will be effective starting October 2018.
The impact of these changes in both the US and EU will likely take a while to have an effect. It is doubtful that busy physicians will have the time to check these databases, so the initial impact will likely be manifested in how pharmaceutical companies use this publicly posted information and data.
What Is the Potential Impact on Publication Planning?
It is no longer possible, nor desirable, to hold on to results and time data publication/release at congresses in tandem with product launch or competitor launch. Holding data not only raises concern around the validity of data, but may also imply Machiavellian manipulation of information, which at best may simply be delayed disclosure, but at worst could be viewed as concealing or “spinning” information for commercial gain. Since primary data results will be posted on a clinical trial database 12 months after the PCD, it is likely that more research sponsors will now want to publish a primary manuscript containing the same results, within a similar time period. Such publications would allow the context of the results to be fully explained, and for expert advice and guidance to be given – critical information that cannot be posted on clinical trial websites. Since many primary publications take around six months to develop prior to submission, speed will be of the essence. For other types of data, such as post-hoc analyses, which may require further analyses to understand the data, delays may be more acceptable.
From a publication planning perspective, this means that upfront and early planning is going to be essential. There will be a greater need to understand the literature and gap analyses earlier in the lifecycle to be able to effectively prepare for data releases, and meet objectives and timelines for all study phases (Figure 2 below). Objective, fair, and balanced reviews will need to be considered well in advance, and fill a very real unmet educational need. This is likely to be critical for first-in-class products where reviews may be essential to build greater knowledge of a new class of products with the potential to meet that need. Consequently, robust literature gap analyses may be necessary at an earlier stage in the process. Indeed, many companies now perform a legally approved needs assessment before embarking on review publications, to ensure that they cannot be misinterpreted as commercial market-shaping pieces. Understanding the therapeutic and competitor landscape will still have a place, to help inform key upfront decisions with authors regarding target congresses and journals.
Since the pressure will be on to publish manuscripts of clinical trial data within a shorter timeframe, publication teams will need to engage with investigators and authors from a much earlier stage in the publication planning process, to have discussions about the potential data, the proposed manuscript, and target journal. Publication planning also needs to be agile enough to react quickly to meet the needs of data-hungry healthcare providers if efficacy or safety signals arise and need to be understood; therefore, regularly scheduled (eg, monthly) publication planning meetings and updates are essential.
So, what about “story flow?” This terminology within our current publication environment is dated, inappropriate, and should be avoided. However, it will still be advisable to have agreed medical or publication objectives developed upfront, based on objective analyses of the therapy area, input from external experts, and medical information requests. Publications may be planned to meet these medical or publication objectives. These objectives, which could be mapped over time, will be important to drive a logical flow of information to ensure physicians and patients are educated in an optimal way. In addition, a scientific platform with clear and concise scientific statements, based on robust evidence, will help ensure consistent and aligned terminology, where appropriate, and may support the more rapid development of publications.
Speed is likely to become one of the most important factors in publication planning. The driver for this is to provide the medical and scientific communities with complete, balanced, and transparent data in a timely manner, which allows them to make informed and appropriate decisions for people with medical conditions. However, with careful upfront planning with internal teams, authors, and investigators, there is no reason why publications cannot support medical or publication objectives, including clear and concise terminology, while still being delivered in a timely fashion.
- US Food and Drug Administration. Full text of FDAAA laws. Available at: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FoodandDrugAdministrationAmendmentsActof2007/FullTextofFDAAALaw/default.htm. Last updated August 17, 2009. Accessed June 29, 2017.
- Battisti WP, Wager E, Baltzer L et al. Good publication practice for communicating company-sponsored medical research: GPP3. Ann Intern Med. 2015 Sep 15;163(6):461-4. doi: 10.7326/M15-0288.
- International Federation of Pharmaceutical Manufacturers & Associations. New industry position requires submission for journal publication of all phase III clinical trials. Available at: https://www.ifpma.org/resource-centre/new-industry-position-requires-submission-for-journal-publication-of-all-phase-iii-clinical-trials/. Last updated June 10, 2010. Accessed June 29, 2017.
- Graf C, Battisti WP, Bridges D, et al. Research methods & reporting. Good publication practice for communicating company sponsored medical research: the GPP2 guidelines. BMJ. 2009 Nov 27;339:b4330. doi: 10.1136/bmj.b4330.
- ClinicalTrials.gov. Checklist for evaluating whether a clinical trial or study is an applicable clinical trial (ACT). Available at: https://prsinfo.clinicaltrials.gov/ACT_Checklist.pdf. Last updated June 14, 2017. Accessed June 29, 2017.
- Zarin DA, Tse T, Williams RJ, et al. Trial reporting in ClinicalTrials.gov — the final rule. N Engl J Med. 2016 Nov 17;375(20):1998-2004. doi: 10.1056/NEJMsr1611785.
- European Medicines Agency. European Medicines Agency policy on publication of clinical data for medicinal products for human use. Available at: www.ema.europa.eu/docs/en_GB/document_library/Other/2014/10/WC500174796.pdf. Last updated October 2, 2014. Accessed June 29, 2017.
- European Commission. Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC. Available at: https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-1/reg_2014_536/reg_2014_536_en.pdf. Last updated May 27, 2014. Accessed June 29, 2017.