What does mainstream media say about enzyme replacement therapies?

Abstract

Introduction

Enzyme replacement therapies (ERTs) are expensive drugs that can be used to treat certain inherited diseases. ERTs are not universally covered across provinces and costs are beyond the means of most patients. Media reports are commonly used to lobby for provincial ERT funding for specific patients. As physicians may be confronted with these media reports by patients, this study explored medical reporting regarding ERTs in print media.

Methods

Canadian Newsstream database was searched for articles about three ERTs—Elaprase™, Naglazyme™ and Vimizim™. Articles meeting inclusion criteria were reviewed for data regarding efficacy and adverse events, mention of role of health care professionals and medical information sources. Thematic analysis explored how efficacy was described within the articles. Data from product monographs and recent meta-analyses served as a basis for comparison.

Results

Of 57 articles retained for the study, 9% mentioned clinical trial data regarding drug efficacy; 7% mentioned adverse events. Only 23% of opinions about medical necessity or efficacy of the drug were from a physician. The majority were those of politicians. Information describing the condition was accurate in 90% of cases, although usually incompletely.

Discussion:

Incomplete or inaccurate reporting about efficacy and safety may influence families that appear to be candidates for ERT. Poor reporting of medical information may also influence the social pressures placed on the government and affect funding approval for these drugs. Physicians should be aware that their patients may be exposed to misleading information.

Canada has proposed that a rare disease be defined at a prevalence of less than 1 case per 2000 people (1,2), recognizing that there is no internationally agreed definition. Before 1983, there was little incentive for pharmaceutical companies to partake in rare drug development, given the high cost of drug development and a very limited market (3). Since 1983, however, a number of countries have enacted orphan drug frameworks and the number of orphan drugs being brought to market has increased from ~1 per year to ~110 per year (1,3).

Over the past decade, one class of orphan drugs, enzyme replacement therapies (ERTs), has frequently been the focus of mainstream media attention. ERTs work by providing an exogenously produced enzyme to correct an inherited metabolic deficiency. They are delivered intravenously, and can be successful in slowing some aspects of the multisystemic diseases they treat.

Treatment is generally initiated in childhood and is often lifelong. Drug costs are typically $200,000 to $720,000 per year per patient. The drugs must be approved by Health Canada to be used in Canadian patients; however individual funding decisions are the responsibilities of the provinces or private insurance companies. High costs make government funding decisions challenging. This dilemma is captured well by a 2014 Globe and Mail article:

“Families of patients with rare diseases have become increasingly vocal in the past decade and exert considerable pressure on federal and provincial governments to fund these expensive medications. They organize rallies, meet with politicians and use social media to call attention to the issue of rare diseases. In some cases, drug companies pay or provide other support to patients or advocacy groups to use personal stories to lobby for public coverage of rare disease medications...The dilemma facing government policy makers is which of these exorbitantly priced, but potentially life-altering, medications it should pay for. In some cases, the benefits of rare disease drugs may be only marginal, despite persuasive anecdotes from vocal patient advocates” (4).

Given the increasing role of media pressure on rare drug approvals, this study aims to explore medical reporting about orphan drugs—specifically ERTs—in the mainstream media.

METHODS

In September 2016, Canadian Newsstream database was searched using trade names for three rare drugs—Elaprase™ (idursulfase), Naglazyme™ (galsulfase) and Vimizim™ (elosulfase alfa), which treat Hunter, Maroteaux–Lamy, and Morquio syndrome, respectively. These drugs were chosen as: 1) A decision was made to limit articles to paediatric populations to reduce heterogeneity; and 2) The above drugs are the newest ERTs to enter the Canadian market for the paediatric population. Source type was limited to newspapers. Only articles published by a mainstream media outlet (e.g., Calgary Sun, Toronto Star, etc.) and intended for the general public were included. Retrospective date limits were not set.

To further minimize heterogeneity, articles were excluded if they did not focus on a specific patient or the ERT itself (e.g., articles about fundraisers), or they focused on an experimental therapy or method of delivery. Articles were also removed if they were duplicates, the full article could not be obtained, were published on industry news wires or in a trade journal, or were letters to the editor. Titles were screened to identify industry press releases. Otherwise, all articles were read in full when comparing against inclusion/exclusion criteria.

Included articles were reviewed for data regarding efficacy and adverse events, and sources of medical information. Inductive thematic analysis was used to explore how the articles discussed efficacy. Specifically, articles were read in entirety and relevant content was extracted into a database. For each article key theme(s) were assigned. In a second review, similar themes were combined, where appropriate. Articles were also searched for specific statements about the drug effect (e.g., life-saving, -changing, -sustaining, normal life, crucial, critical) as these statements were not always included with the efficacy description. Article review, data extraction and thematic analysis were completed by one author. Where possible, data were also extracted from product monographs (5–7), as well as from recent meta-analyses, to serve as a basis for comparison. Medline (Ovid) was searched using both the trade and generic drug names as keywords in October 2016. The search was then limited to meta-analyses and systematic reviews. The most recent meta-analysis/systematic review was chosen, as this was assumed to represent the most current and comprehensive source of data.

RESULTS

The search strategy identified 46 articles on Elaprase, 29 on Naglazyme and 26 on Vimizim from Canadian Newsstream database published between 2006 and 2016. Of these 101 articles, 57 satisfied inclusion criteria. Forty-four articles were excluded as they were duplicates (20 of 44), letters to the editor (3 of 44), about experimental therapy (3 of 44), about an adult (1 of 44), the primary focus of the article was not a patient or the ERT (16 of 44) or a full-text could not be obtained (3 of 44).

Medline (Ovid) and Pubmed literature searches identified four unique articles on Elaprase, and three unique articles on Naglazyme. The most recent meta-analysis for each drug was kept (8,9). No results were found in Medline (Ovid) for Vimizim. One result was found in Pubmed; however, its topic was not relevant to the current study. As no systematic reviews for Vimizim were found, the most recent randomized controlled trial was used (10).

Efficacy

Eighty-nine per cent of articles (51 of 57) included a description about the efficacy of ERT. Most, however, were informal descriptions that did not reference data from clinical trials or medical literature. For example:

“Without treatment, sufferers see their life expectancy cut short. […]Though not a cure, weekly infusions could help prevent Aleena’s symptoms from getting worse…” (11)

“It can cost about $200,000 a year and wouldn’t cure his disease, but it has been shown to increase physical endurance in some patients, which can improve their quality of life.” (12)

Only 9% of the newspaper articles (5 of 57) specifically referenced clinical trials, and only one provided any quantitative data about the magnitude of the effect. This was a single data point, which is consistent with the data presented in the product monograph:

“After a year, the participants who received Elaprase could breathe better and could walk 35 metres farther in six minutes than those who received the placebo.” (13)

Most articles did not report specific data regarding drug efficacy; therefore, a thematic analysis was undertaken. The most common correct themes were: ERT improves physical symptoms (51%), and ERT slows disease progression (14%). The most common incorrect themes were: ERT stops progression (33%), that the condition will be fatal only if the patient is not treated (14%), and that ERT treatment will allow for a normal life (5%) (Figure 1, Table 1).

Figure 1.

Major themes reported in articles regarding effect of ERT. As some articles had more than one clear theme, totals exceed 100%.

Table 1.

Possible symptoms of the medical conditions that are treated by ERTs, in comparison to the drug effect, as reported in the media, product monograph, and systematic reviews

Several articles contained emotionally charged statements regarding the effectiveness of the drug. Compared to the clinical trial data available, most of these statements exaggerated the efficacy of the drug:

“Carolle Mazerolle was cleaning her house for Christmas when the call came that could save her young son’s life.” (14)

“A government member of the Alberta legislature added his voice Tuesday to the demand for immediate action to save a young girl wasting away due to a rare enzyme deficiency.” (15)

Fourteen per cent of articles incorrectly refer to the drug as ‘life-saving’. ‘Potentially life-saving’, and ‘life-changing’ were each used in 3.5% of articles. ‘Crucial’ or ‘critical’ were used to describe the drug in 5% of articles. Another 5% incorrectly imply that ERT treatment will provide the patient with a ‘normal life’; however, ERTs modify only a portion of possible disease symptoms. In contrast, only 40% clearly state that ERTs are not a cure.

A comprehensive summary of ERT efficacy as presented by the media, reported in the product monographs, and in recent meta-analyses is presented in Table 1.

Adverse events

Only 7% of the articles (4 of 57) mentioned the possibility of adverse events. Two of these articles were quotes from families, whereas the remaining two appeared to be from medical sources.

Sources of medical information

Forty-two per cent of the articles contained a quotation about the medical necessity or efficacy of ERT, but only 23% of quotes came from a physician. The highest number of comments regarding medical necessity or efficacy of ERT came from politicians. Patient advocates provided medical information as often as medical doctors (Figure 2).

Figure 2.

Source providing quotations regarding medical necessity or efficacy of ERT, shown as a percentage of number of articles, and a percentage of number of quotes. Some articles included more than one quote.

In many cases, medical information was incorrect, or overstated the impact of the drug:

“Every one of these patients is seeing improvements…” (16) - Politician

“McFadyen has said that while the treatment is not a cure, it will keep the children alive while efforts to find a cure are made.” (17) - Patient advocate

In some cases, nonphysicians provided accurate information:

“Reviews on Vimizim are still up in the air, Boudreau said. “There’s a fair bit of misinformation that circulated as part of this story,” the minister said. “It’s not a lifesaving drug. It’s not a cure. It could improve a person’s condition but it’s certainly not a cure. No province covers it in a blanket type of way.”” (18) - Politician

“Untreated, he will experience significant decline. As the patients grow older, some of their symptoms become irreversible. Ultimately, he will be wheelchair-bound if his joints become so stiff that he can’t move.” (19) - Patient advocate

Ninety-one per cent of articles presented a brief description about the symptoms and/or pathophysiology of the disease. Of these, the description was accurate in 90%, although often incomplete. In the 10% with significant errors two articles incorrectly referred to the condition as a ‘blood disorder’ and three gave an incorrect name for the enzyme.

DISCUSSION

This study showed that most newspaper articles present a very fragmented view of ERTs. The information provided is often incomplete, or exaggerated, and fails to give a comprehensive impression of the benefits and limitations of ERT. Reporting about the efficacy and safety of ERTs was often incomplete or inaccurate (Table 2). Thus, based on available data, reports that the drug is ‘life-saving’ or halts disease progression are erroneous, and even articles that report ‘slowed progression’ or ‘improved physical symptoms’ do not give a comprehensive picture of the drug effects on treating a multisystem illness (Table 1). The obvious truth that major comorbidities unaffected by the drug may contribute greatly to poor quality of life was not discussed.

Table 2.

Information reported in mainstream media articles

	Percentage of articles (N=57)
‘Describes’ efficacy	89%
References clinical trial	9%
Reports quantitative data	2%
Reports possibility of AEs	7%

Mainstream media reporting may impact perceptions and expectations of families with rare disease who may be ERT candidates. Thus, based on the information reported in the media, families may present to paediatricians, family doctors or genetics clinics with unrealistic expectations regarding the benefits of the drug, and little prior knowledge of the potential harms. This can lead to confusion by families who may have had a recent diagnosis of one of these rare disorders. This situation can be damaging to new or existing patient–physician relationships, because the physician must attempt to correct misconceptions using data from scientific literature without removing hope.

This type of reporting may also place undue pressure on governments. In Canada, the Common Drug Review board is the first to evaluate new drugs for their clinical and economic impact. However, the decision to reimburse a drug remains within the jurisdiction of each province. The public can be involved in coverage decisions within BC, Quebec and Ontario since they allow submissions from patient organizations and have a public representative on their committees. In almost all jurisdictions, there is an established process for case-by case reviews where the request is often made by the prescribing physician (20). Since these decisions may be influenced by public opinion, there is a potential for bias based on media reporting as lay-people may not be able to access, or fully appreciate the complexities of, clinical trial data, and may use mainstream media as their primary information source.

Our findings are specific to ERT reporting, but they are certainly part of a broader concern. Multiple studies have examined the accuracy and nature of media coverage within the medical field. Such articles consistently identify shortcomings with media reporting including inaccuracies, incomplete data and overemphasis of benefits (21–25). One 2003 study by Cassels et al focusing on new prescription drugs, determined that 62% of articles gave no quantitative data of the benefit or the harms (21). This also shows that the challenges with medical reporting are a long-standing concern in Canadian media. Under-reporting is not only limited to pharmaceuticals. Studies on both pharmacogenetic testing and genetic research found that an over-emphasis on benefits and under-representation of risks (22,24). This is the first study to focus on ERTs or orphan drugs. The identified issues with media reporting may be particularly relevant to governments, healthcare professionals, patients and families, given the high drug costs and the potential for public representation in their approval.

We found that statements about medical necessity or efficacy of a drug were most often obtained from a politician, rather than a physician. An article by Wilson et al found that Canadian newspapers tended to rely on expert opinion rather than published medical information (26). Furthermore, a study by Schwartz et al showed that when high quality press releases were issued by medical journals, the quality of associated newspaper articles improved (27). Physicians have a duty, in terms of their responsibility to society, to ensure that public information on any treatment, particularly a novel and expensive one, is accurate. Thus, we would encourage physicians and physician organizations to work collaboratively with journalists and media organizations. Well-informed physicians may consider agreeing to media interviews, proofing media articles, contributing to press releases or writing for public media.

We sympathize with patients and families dealing with orphan diseases. Accurate information may be difficult to find, and, as we have shown, is unlikely to be in the mainstream media without changes in attitudes. We would suggest that patient organizations, professional organizations and governments collaborate to produce information that is evidence-based and that avoids generating conflict. New drugs are urgently needed for orphan diseases; we must ensure that we support those that are likely to help patients.

Funding: None.

Competing Interests

None.

IM reports the following from AbbVie Canada: grants, Advisory Board and travel to present results. He also reports grants from Regeneron outside the submitted work.