Ocular gene transfer in the spotlight: implications of newspaper content for clinical communications

The field of gene transfer, colloquially known as ‘gene therapy’ , has followed a trajectory of high hopes and high profile failures. Historical abuses, including non-disclosure of serious adverse events and highly publicized conflicts-of-interest, have damaged its reputation[1–3], eroded public trust, and presented significant setbacks for its clinical development[4, 5].

Ocular applications may yet rescue the reputation of gene transfer with successful clinical trials beginning in 2007. Phase I clinical trials for Leber congenital amaurosis (LCA), a rare, blinding retinopathy, established both indexes of safety and improved visual function, despite the small size and safety focus of first-in-human phase I clinical trials[6–8]. Phase I trials are followed by larger phase II trials that continue to test safety and establish preliminary measures of efficacy. Phase III trials, most commonly randomized, controlled trials, are then statistically powered to test efficacy for primary (e.g., visual acuity) and secondary (e.g., retinal imaging) outcome measures. Sustained safety results for LCA[9] have led to a phase III clinical trial at the University of Pennsylvania, which is currently recruiting children (clinicaltrials.gov: NCT00999609). Developments in LCA trials have served as an impetus for further clinical trials for related ocular diseases[10], including Stargardt disease (clinicaltrials.gov: NCT01367444), retinitis pigmentosa (clinicaltrials.gov: NCT01482195), Usher syndrome (clinicaltrials.gov: NCT01505062), and choroideremia (clinicaltrials.gov: NCT01461213).

These recent advances in ocular gene transfer have triggered media attention[11], raising patient hopes[12] for the mediation of previously untreatable genetic diseases. News media are the most accessible source of information on biomedical research for the public and patients[13]. Media coverage, therefore, if exaggerated or misrepresentative of gene transfer, may influence societal and patient expectations.

News media are often blamed for distorting the impact of biotechnology research through overly aversive or favorable communications[13, 14]. Media use frames (simplified, interpretive representations of an issue) to highlight the importance of an issue and how it should be addressed[15]. Frames often bias contentious scientific issues by placing greater emphasis on certain considerations while omitting others[16]. For example human embryonic stem cell research may be framed as ethically unjustifiable for its destruction of embryos or as an ethical imperative to provide cures for otherwise incurable diseases[17, 18]. Biomedical reporting is often criticized for its framing that uncritically celebrates progress in research[19]. Such framing emphasizes benefits over risks[20], and omits crucial information such as funding sources and potential conflicts-of-interest[21, 22]. The coverage often presents pre-clinical research (i.e., in-vitro or animal studies) as an imminent therapy or cure[20].

From a clinical perspective, the uncritical progress frame may lead clinicians, patients, and their families to form high expectations, only to be disappointed when reality falls short of hope, causing disillusionment among clinicians and despair among patient communities[23]. In the context of clinical trials, overly positive media coverage about research in progress may present challenges to enrolment and informed consent in ongoing or subsequent clinical trials by heightening patient expectations for therapeutic benefits[24]. In particular, potential participants may misunderstand the safety focus of early-phase trials and expect therapeutic outcomes[25].

As ocular gene transfer clinical trials for hereditary retinopathies increase in number and reach phase III, attention must be directed at facilitating ethical communications of risks and potential benefits for recruitment of clinical trial participants. Such communications will occur in an environment of heightened media coverage, with media influencing patient and public perspectives about pre-clinical and clinical gene transfer research. Here, we ask how newspaper articles report on ocular gene transfer for hereditary retinopathies, exploring errors of omission and biases in representations of framing, risks and benefits, as well as therapeutic potential. Our analysis suggests the need for clinicians to account for media coverage in their communications with patients, especially in the context of clinical trial enrolment. Evidence-informed communication strategies set against the media landscape will ensure the ethical translation of this biotechnology as it moves forward to clinical application.

We used pre-determined coding categories for our content analysis. The coding categories were modified from pre-existing studies about media coverage of health research and biotechnologies[28, 29] and adapted to include issues raised in similar studies[30–32]. Furthermore, the coding categories were developed in response to issues raised by forty-one semi-structured interviews with stakeholders of a phase I ocular gene transfer clinical trial (choroideremia patients, clinicians, and patient advocates). A thematic analysis of these interviews revealed high therapeutic hopes, limited attention to risks, and confusion about the timelines for the clinical application of gene transfer among patients[33]. The final coding categories investigated the attention structure of newspaper articles (word count, page number, news format), disease representations, key categories of spokespeople, one dominant frame for each article, use of human-interest stories, tone of coverage, description of methods, representations of timelines for translational research and clinical implementation, and representations of risks/benefits. Tone of coverage was determined using a combination of quantitative (number of benefits stated versus number of risks) and qualitative (prominence and stated magnitude of benefits versus risks) assessments. If the article stated more benefits than risks, its tone was positive. However, where benefits and risks were equal in number, we considered their respective magnitude. For example, a benefit of “cure for blindness” versus the economic risk of “expense of the clinical trial” also indicated a positive tone.

A research assistant coded all articles, and one of the authors [SB] independently coded 19% to verify that a second coder would arrive at the same conclusion as the main coder. We calculated Cohen’s Kappa for inter-coder reliability (SPSS 18: IBM). Kappa scores ranged between 0.71-1.0, displaying acceptable inter-coder agreement[34]. To accommodate the small sample size of Canadian newspaper articles, we used Fischer’s chi squared tests (STATA 11: StataCorp 2009) to assess differences in coverage between countries. We used a Kruskal-Wallis Analysis of Variance (STATA 11: StataCorp 2009)—a non-parametric alternative to a one-way analysis of variance—to assess differences in the median number of benefit and risk representations between countries. We combined articles from the three countries when there was no significant difference in coverage (α = 0.05).

Our analysis of newspaper coverage of ocular gene transfer identifies persistent challenges posed by overly positive representations of experimental biotechnologies in all three countries analysed. Sensationalism in the news media is seldom present as blatantly inaccurate reporting[20, 28, 31]. Instead, as for ocular gene transfer, overly enthusiastic or exaggerated claims are evident through biased framing, errors of omission, and an emphasis on benefits over risks. Such overly optimistic reporting serves to discredit media claims[39] and build heightened social expectations about the promise of emerging biotechnologies[40]. As such, the research community, policy makers, and ethicists view a lack of balance in media reporting as a major shortcoming[20].

Our analysis of newspaper coverage of ocular gene transfer identified minor differences in coverage in Canadian, UK and US print media, but the same essential concerns persisted. Coverage in all three countries focused on human-interest stories, dominant framing as a “celebration of progress”, and had limited discussion of risks, research design, conflicts-of-interest, funding sources, and research timelines. US news articles were least likely to discuss the genetic cause of retinopathies and were most inaccurate in their depiction of the purpose and methodology of gene transfer. Differences in coverage patterns were likely due to the number of articles in newspapers of varying quality per country (e.g., national versus local and broadsheet versus tabloid) and attention to local research. For example, Canadian articles reported more pre-clinical research, reflecting the state of gene transfer in Canada.

Recommendations to address these media challenges are many and include describing scientific roadblocks and the possibility of findings being invalidated by further studies[30]; encouraging reporters to consult independent sources of information about the implications of scientific advances[41]; and encouraging researchers to disclose conflicts-of-interest to reporters[21, 22]. Proposed educational strategies to promote balanced reporting include training researchers to “stick to the facts” when communicating with reporters; training graduate students—as future spokespeople—in effective science communication strategies[20]; inviting reporters to scientific conferences; and creating accessible materials to educate the news media about scientific advances[42].

Unfortunately, these recommendations do not adequately account for the nature of news media, which, as businesses, face their own pressures. Journalists produce copy within limited deadlines and compete fiercely for editorial and public attention. While increasing web content expands potential to provide further background material, print and television media still face space or time constraints. Our findings on frames and emphasis of benefits over risks highlight that ocular gene transfer is seen as a “good news” story for the visually impaired and their families. Our analysis confirms that decades of recommendations and initiatives to improve the tenor and content of science journalism have resulted in limited discernible improvement, at least, in the context of ocular gene transfer. As a result, recommendations may be more tractable at the level of clinical communications between clinicians and patient communities. Here, we first place our results in the context of other studies and then recommend the development of communication strategies between clinicians and their patients, especially potential clinical trial participants, that operate within the landscape of overly optimistic media coverage.

This study shows little improvement in science media communication in the past decade, despite initiatives to improve journalism on novel health technologies[20, 28, 30, 31, 41, 42, 47]. Media reports continue to be overly optimistic and framed as human-interest stories, whether from the perspective of the heroic researcher or hopeful patient. We therefore reiterate that clinicians and researchers, in their encounters with the news media, should be factual, balanced in addressing both risks and benefits, disclose funding sources and conflicts-of-interest, provide realistic timelines, and discourage curative speculation when research is either in early stages or when a cure is not theoretically possible. As a further incentive for moderated media communications, we support Kimmelman’s[66] recommendation that institutional review boards require investigators of clinical trials to submit a portfolio of their press releases as a component of ethics review[66].

At a more practical level, however, and one that is directly in the control of researchers/clinicians, the onus must be on these stakeholders to address the backdrop of media coverage in the context of ongoing clinical care and clinical trial enrolment. In particular, researchers and clinicians must distinguish between the goals of research, of the phases of clinical investigation, and treatment. Additionally, clinical communicators must counter media messaging, emphasizing to their patients that a cure will not be afforded through gene transfer alone. Taking media communications into account when discussing the potential of ocular gene transfer clinical trials will promote ‘informed hope’ among patients in the context of clinical care[67], informed consent among research participants in the context of recruiting trials, and facilitate the ethical translation of this biotechnology as it moves towards clinical application.

Ms. Shelly Benjaminy has a BSc in molecular genetics and an MSc in health policy from the University of Alberta. Her research explores multi-stakeholder priorities for the translation of novel biotechnologies. Dr. Tania Bubela has a PhD from the University of Sydney in biology and a JD from the University of Alberta. She researches in the field of health law and policy as an Associate Professor, School of Public Health, University of Alberta.