Unveiled: how to win their attention

pharmafile | July 2, 2004 | Feature | |   

Sir Arthur Conan Doyle once wrote: "It is a capital mistake to theorise before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts."

His statement still rings true for the emerging clinical data that is vital if new products are going to carry any weight with clinicians and prescribers.

The presentation of clinical data is an essential component in the development of new compounds and a well-worn route for companies who want an evidence-based backdrop for their new drugs.

By accurately disseminating positive research findings that make the case for previously unproven products to make the desired impact on patients and healthy volunteers, the presentation of clinical data is the process where noise starts to build up exactly where the manufacturers want it: in the medical community of specialists and physicians in the appropriate therapeutic area. It's the stage where researchers start building awareness from facts rather than from theories.

There are several avenues the industry can take. Arguably the most effective way of presenting new product data is by getting it published in high prestige, influential medical journals. This can often be a lengthy, tireless process and can often take over a year before data has passed rigorous screening by peer review panels before it makes it onto the pages.

Then come the traditional sponsored symposia whereby companies will often pay a huge amount of money to a congress or society so they can have a two-hour slot which acts as a platform to bring in opinion leaders to talk about any issues (usually centred around their own products) they would like to raise. This is possibly the least favoured route, and definitely the one most open to criticism, due to the industry's overt influence, and appears to be on the way out.

Another platform, which is predominant in the US but still relatively untapped in Europe is the Continuous Medical Education (CME) programme. Highly regulated, and seen as scientific and educational with minimal industry involvement (only generic names are allowed to be used), this is regarded as the way forward in communicating clinical data.

It can also be argued that clinical trials themselves are a methodology to communicate data. After all, they require the involvement of the relevant doctors and researchers, who as a result become more familiar with the medicines being tested.

All different methods of presentation, but from a product point of view, the data remain the same. This begs the question of whether it is simply a case of ensuring the data is solid, accurate and reliable and letting it sell itself to the experts or whether certain techniques are more effective than others.

Jan Heybroek, vice president operations at CME provider Imedex believes that the recipients of clinical information are savvy and experienced enough to absorb the message that is being sent to them in the correct context.

"I think all methods of presenting data are effective in terms of being useful communication tools," he says. "It just that the sender [ie, the company] has to be aware of what their end result is going to be. If they really want to be effective, they have to work the different routes but also tailor the message to make sure it is being accepted in the light that they intend it to be."

Therefore, the traditional sponsored symposia is often construed by physicians as having an 'advertorial' feel and this can often mean a percentage of the message is lost.

"If an individual perceives something as advertising, they can scale down the message by as much as 80%," says Mr Heybroek.

Trevor Sills, account director at Healthworld Communications Group agrees: "Clearly, it fairly unrewarding for doctors to attend meetings just to be spoon-fed."

Meetings

According to Mr Sills, scientific meetings (CME, sponsored symposia) hold one distinctive advantage over publication in medical journals time.

"What's intriguing is that while the journal peer review route can take over a year, much to the frustration of product managers, meetings provide the opportunity and platform to get the data out into the clinical community much earlier," he says.  "I think this is one of the best reasons for exposing and disclosing product data at meetings.There are certain rules to follow when presenting data at meetings."

As Mr Sills explains, the whole raison d'etre of scientific medical conferences is to provide information on new drug treatments, new advances in therapies and to keep people abreast of discovery programmes. In short, the onus is on giving doctors a rewarding experience where they feel they have come away with new, fresh knowledge.

"Many people go to meetings expecting to hear about advances in how practitioners can best treat their patients according to what new information is available," says Mr Sills. "By and large, what underpins the prestige of meetings is how much novelty is disclosed and exposed. Meetings are deemed exceptional and held in high regard if they contain ground-breaking news, such as data supporting new therapeutic principles or the use of existing treatments in new populations and new indications or potential new treatments still in the early discovery stage."

Companies also have to be careful not to repeat information in meetings. After all, it can be very damaging if doctors hear the same things they heard at the same annual conference the previous year, albeit it slightly reworked and rehashed.

Then, of course, there's the question of the data itself: doctors are always happy to hear about the latest clinical trials of products against placebo. But this doesn't detract from the fact that most of them want to see much more comparative head-to-head studies.

"The industry doesn't embrace direct drug A versus drug B trials, which the practitioners see as the most important," says Mr Sills. "It's ironic as most clinicians who attend meetings are not purely researchers and have clinics full of patients. They want to know that if for a particular therapy they can have ten treatments, which one is the best according to the criteria they see as important as evaluated in a head-to-head trial."

Key Opinion Leaders

Presenting data is as much about who is presenting it as the data itself, particularly at early clinical development stage. It is seen as critical for the industry to partner with the most prestigious research institutes and get key opinion leaders on board to bolster the message with added credibility.

"Data is data, but in terms of acceptance of the message, there's a much better response when you have a respected well-known professor delivering it,"says Mr Sills.

My Heybroek says that at CME events, the presence of key opinion leaders means delegates often feel honoured to be invited.

"There is often communication between the chair (usually a prestigious key opinion leader) and the speakers in terms of what can and cannot be presented," he adds. "It is almost like a self-cleansing or self-limiting mechanism in that people want to make a good impression when presenting their data and not be seen as a spokesperson for any particular cause."

The multi-sponsored, 'hands-off' approach of CME has already taken off in the US, but is still relatively untapped in Europe. Many US attendees have to pay a registration fee as well as travel and accommodation expenses, highlighting the fact that they have a strong educational interest in events. Invites from the pharmaceutical industry are strictly forbidden.

"CME is a wonderful and transparent opportunity for interaction and debate between opinion leaders, prescribers and the pharmaceutical industry," enthuses Mr Heybroek. "Our events do not have 10,000 attendees, they are smaller, more personal events based on interaction and discussion it's here that the true value of communication is seen and established."

Journals

Generally regarded as the gold standard for disseminating clinical research results, publishing in a reputable medical journal such as the Lancet, the BMJ or the JAMA has courted controversy over the last few years. Effective publication planning should commence around phase I so that scientists and clinicians can be made aware of a product's potential well before its launch.

"I think every product manager wants to get in this type of journal because they know that by getting data published there, it can raise awareness and influence management and treatment practices," says Mr Sills. "They are taken seriously by opinion leaders, practitioners and clinicians because they trust and accept that published data is accurate, honest and most importantly, been subject to the scrutiny of an intense review committee."

Papers not only have to get past the watchful eye of the editor, who ultimately decides whether they are relevant to the readership, but also have to survive the rigorous peer review process, which usuall involves two or more anonymous experts. While this is normally enough to satisfy the scientific community of their credible and authoritative nature, doubts remain.

Both the BMJ and the Lancet have raised questions recently about how much influence the industry is exerting over the publication of clinical trials. In January, Lancet editor Richard Horton announced stricter rules governing the submission and editing of clinical trials papers in its pages. Certain investigators in the past have been guilty of not declaring conflicts of interest while some editors have been guilty of bowing to covert or explicit pressure by some companies to go easy on their clinical data.

Mr Sills says that the furore over undue influence strengthens the argument that the industry has to be much more transparent both with clinical investigators and editors. He believes that the pharma industry must continue to embrace the spirit of co-operation and work openly with investigators, otherwise it risks getting publication of clinical data refused.

"Companies have to make sure they are not just feeding data selectively otherwise they will just continue to go down the spiral of mistrust," he says. "Opinion leaders who read the journals want an absolutely honest account of trials. If an author cannot declare in his submission letter that he has had open and positive collaboration with the sponsor in respect of data analysis, data review and manuscript generation then how can it be seen as his own work?"

In the industry's defence, Mr Sills points to a 2001 study by the US Tufts Center for the Study of Drug Development, which put the cost of bringing a new drug to market at $802 million. According to the analysis, for every 13 drugs that start out in animal testing, only one ever makes it to market. Most worryingly it found that pharma companies are earning a pitiful 5% ROI in finding new drugs. "When you make that kind of investment, it natural that you will work pretty hard to get it back," he says.

ABPI spokesman Richard Ley denies that some member companies have been trying a bit too hard to recover their money: "We have very high standards in our industry and I know it's deeply resented within companies any suggestion that they are somehow compromising those standards not just on the commercial side but the ethical side."

He insists that the ABPI has always desired crystal clear transparency from research authors with industry connections. He also points out that the medical journals are the ones who decide what data to publish but are the first to complain when something negative comes to light.

"Some of the articles the BMJ has commissioned and published have been quite unacceptable, in the sense of publishing attacks on the industry without giving it the chance to correct the misinformation that's been evident in those articles.

The future

So what does the future hold for presenting and publishing clinical data? Yet again 'transparency' appears to be the key word. The medical community would like to see more negative data available as well as safety and tolerability studies. The ABPI set up a voluntary web-based register of clinical trials last year but member response has been disappointing.

In these times of increased scrutiny, more companies may start to accept that CME will be the most effective route for providing balanced, unbiased and fair information to prescribing physicians.

Perhaps the key to the issue is how well companies manage and adjust their own expectations of what they can gain from presenting data in line with the new climate.

Mr Heybroek admits some companies may initially struggle with the 'hands-off' approach that the new rules demand: "Some companies may come from an environment where they expect to have more of an input into programmes but that is no longer possible. However, most have adapted to the new rules and environment and that bodes very well." 

Accentuating the positive (Case Study)

Pharmaceutical companies spend a lot of time and money designing clinical trials to measure drugs against specific criteria, and usually have a fair idea of what the results will be.

One of the most remarkable examples of things not going exactly to plan was a recently published Bristol-Myers Squibb sponsored study of its statin Pravachol against the market leader, Pfizer's Lipitor.

Results from the PROVE-IT study were presented at the American College of Cardiology's Annual Scientific Session in New Orleans in April 2004 and showed Lipitor clearly superior to Pravachol in preventing deaths and particularly beneficial for the early treatment of patients suffering from acute coronary syndrome.

Unable to positively endorse Lipitor, lead investigator Christopher Cannon, Cardiovascular Division at Brigham and Women's Hospital could only recommend early and intensive use of statins generally.

Katy Wynn, cardiovascular analyst at Datamonitor, said: "The trial was originally designed to show non-inferiority between Pravachol and Lipitor, but obviously that backfired, which doesn't happen very often."

Although Lipitor is likely to benefit most from the study, Ms Wynn says it is not a disaster for Pravachol because the study did reinforce its profile as the safest statin.

BMS were able to point out that both drugs were generally well tolerated and discontinuation rates were similar but that patients on atorvastatin 80mg had a three-fold increase in abnormal elevations of liver function tests compared to patients on 40mg doses of pravastatin.

"These results were observed in a carefully selected and monitored patient population," said Dr. Cannon. "Physicians must carefully balance safety and efficacy when applying these results to clinical practice."

Alex Wood is a freelance writer