November 2019 | Dice Medical Communications

Every drug has its core clinical papers, and usually a set of ‘less important but maybe useful/interesting’ ones that need to be assessed. For a copywriter, this often means that, at least at the outset of a project, you are faced with a ring-binder full of papers to work your way through. So it goes without saying, that a good scanning technique is a vital tool to be able to get a quick grasp of the strength and breadth of data supporting a particular drug.

This is how I go about it, but there are no doubt other, equally valid approaches.

As an example, for the purposes of writing this article, I have used a study that was published in 2014 here. The study looked at real-world clinical outcomes in multiple sclerosis patients in order to ascertain the ‘value’ of treating with disease-modifying-drugs (DMDs) – either immunomodulatory (IM) or immunosuppressant (IS).

Step 1 – establish the broad credibility and veracity of the study

1.1 Go right to the end and check to see if there were any commercial sponsors: that may nuance slightly the veracity of the data – and the word ‘nuance’ is important here as I am not suggesting that company-sponsored studies are any less rigorous than non-sponsored trials! But it can sometimes be thrown back at you as an objection, so it’s important to be aware of it.

1.2 Where was it published? Is it an obscure journal or more mainstream? This is important because most authors would love their studies to be published in high profile, respected medical journals, but of course that depends on the ‘strength’ of the study. In this case, the Multiple Sclerosis Journal is a credible, disease-specific publication that is endorsed by leading MS research groups such as ECTRIMS and ACTRIMS.

You can also search for the Impact Factor of the journal which will provide you with a measure of its importance or rank based on the frequency its articles are cited. In the case of the MSJ, its impact factor of 5.649 places it in the top 7% of all journals – so very respectable, although admittedly not at the dizzy heights of the NEJM or The Lancet.

To find out more about the subject of Impact Factors, just go on-line, where there is a plethora of useful information. It’s an interesting and informative read. Suggestion: search ‘impact factor of medical journals’

Step 2 – what are the headline findings?

2.1 Go straight to the conclusions in the summary on the first page!

That’s right. Don’t delve into any details until you’ve absorbed the main outcome of the study.

In this case, the conclusion signposts that there could be some very useful findings in this study, from the top-line (to paraphrase: “These drugs work!”) to the more subtle (“They still work, but to a lesser extent, if you delay treatment”). That is a very enticing conclusion for a copywriter, because you can be confident that there will be some useful nuggets of data on display further on in the paper.

Step 3 – look at the top line results

3.1 You might have noticed that we still haven’t gone past page 1 yet, but that’s fine. The paragraph relating to Results in the Abstract gives you some strong clues as to how excited you should be about the data within.

In this case, the very first result that is given jumps out at me. The risks of progression to a major disability milestone are reduced by 94% in patients treated with IM drugs compared with untreated patients. That really whets my appetite – I want to know more!

3.2 Look at the statistics. It can’t be avoided – as dry as they are, such a big result that we just mentioned needs to be statistically credible if we are to use it in any promotional sense. So we head to the main results section of the paper – page 3.

Here, at the foot of the right hand column you can immediately see that this seems to be very solid data from a statistical view point.

The CI 95% figures mean that this reduction might ‘only’ have been 91%, but could also have been as high as 96%, and a p value of <0.001 means that there is less than a one in a thousand chance that this result is purely down to chance and not a treatment effect.

See our article ‘Basic Statistics for Marketers’ if you want to delve deeper into the subject

Step 4 – is the patient cohort credible?

Now that we are excited about the data, we need to check that the patient cohort wasn’t skewed in any way, such that a good outcome was inevitable. This is the point where you have to do a little more in-depth reading.

I usually begin by scanning the Patients and Methods section (page 2), but in this case, I found more interesting information at the beginning of the results section. There is one stand-out paragraph:

What I deduce from this is that the study not only contained a good number of patients, but also that, very unusually, they were all living under similar conditions as Sardinians on the same island. To understand the power of this, imagine if it was a cohort of 316 patients spread across the whole of Italy: that would immediately raise suspicions that patients had been specially selected in some way and such a low number would also undermine the credibility of the findings.

Then delving deeper, table 2 on page 5 reveals that the patient numbers for the group my client is interested in (those taking immunomodulatory drugs and EDSS 3 as the milestone) is still very credible: 1306 treated patients vs. 781 untreated.

Note that this particular consideration is sometimes not an issue. In some of the rare diseases we work with, drugs are often trialled in only a handful of patients by necessity

Step 5 – are there any worrying safety signals?

The efficacy data mentioned above are exciting, but that would be easily undermined if in that same cohort of patients there happened to be a high morbidity or mortality impact. In this case, the study was not designed to reveal any safety signals, so there is simply no mention of safety throughout the paper.

You might think this is unusual, and it is, but the immunomodulatory drugs that were included in the study have been on the market a long time, and their safety profiles have been very well defined in many other studies and treatment databases.

Step 6 – Are there any other major caveats?

Sometimes, when reading a clinical paper, it becomes clear that the authors are themselves slightly ‘uneasy’ about reading too much into the findings because of some inherent flaw in the methodology, or data collection etc., and if this is stated strongly, then you have to take notice of it.

In this paper, the authors quite fairly point out that observational studies per se have their drawbacks, but then they do contextualise this in a positive way.

Conclusion

That quick scan of an important clinical study took about 15 minutes, but if done correctly, it tells the copywriter that this paper is worth more detailed investigation, or if it can be dismissed. It’s a useful skill to master for the busy marketer or medic.

To share your views on this article please contact me directly on neil@dice-comms.co.uk

My career in the pharmaceutical industry began in research and then took a swerve to the commercial side in the early 1980s. So my working life has involved nearly 40 years of studying, selling, marketing and writing about drugs.

Needless to say, pharmaceutical R&D focus and direction has changed dramatically in that time, and hence so too have the drugs that are developed and launched. It’s remarkable to think that in my early stint as a GP medical representative, I was selling a very basic pain killer (a variant of ibuprofen) and a first generation cephalosporin antibiotic – hardly cutting edge medicine!

Over the years there have been some standout ‘super’ brands – Losec and Lipitor instantly come to mind – and usually the reason for them achieving that blockbuster status was the fact that they were very effective (and ‘safe’) at fixing common problems that every GP encountered. But around the turn of the century, it became clear that all the low-hanging fruit had been harvested. Common conditions such as hypertension, asthma, hypercholesterolaemia and others had largely been ‘fixed’ and we see the evidence of that now in the rapid growth of the elderly population. So it was necessary for the industry to focus on more difficult challenges such as cancers, rare diseases, autoimmune disorders and so on.

In this endeavour, the pharmaceutical industry has been phenomenally successful and doesn’t receive the recognition it deserves amongst the general population. This is sad, but industry shareholders around the world probably don’t care about reputation, as long as the commercial returns from this intense R&D investment continue to be realised. So I could have written this article about the ‘best-selling’ drugs of the 21^st century, but instead I wanted to focus on those that have made the greatest medicinal impact – the ones that have changed the way doctors think about disease management and have expanded the horizons of what we believe to be possible. This is purely a personal list and no doubt arguments could be made for lots of others. If you feel strongly that I’ve missed some obvious contenders then please get in touch – I would love to discuss them with you!

Number 5. Adcetris

The mode of action of this drug is a thing of beauty and that’s why it makes my list. It’s not the only modern drug that has an elegant MOA, but for me it just has the edge. The reason is that it can be described in layman’s terms in a way that is easily understandable, for example as follows:

It’s an antibody that carries the cancer drug directly to the cancer and squirts it in to individual cancer cells to kill them. Which means your healthy cells are not harmed.

Such simplicity belies the incredible science behind its development, so it’s important to remind ourselves that this isn’t about science, but people’s lives. In this regard, Adcetris doesn’t disappoint. I’ve heard on the grapevine that oncologists treating Hodgkin’s lymphoma were ‘blown away’ by its efficacy. Just a great story all round.

Number 4. Gleevec

A diagnosis of chronic myeloid leukaemia in the last century was a fairly certain death sentence and the treatments that did exist were harsh and invasive. Enter Gleevec: a once or twice daily pill and bingo – disease controlled. (I know this is a gross simplification, but its availability really was transformational). As part of its mode of action description, I simply love the words ‘programmed cell death’ – a marketer’s dream.

Number 3. Atripla

I’m old enough to remember reading in medical journals of the 1980s reports of a mysterious illness that was soon known as AIDS and fairly soon after, HIV was identified as the cause. It’s remarkable to consider the achievements of the pharmaceutical industry in transforming a deadly disease into a manageable chronic condition in only a few years. The early treatments were unpleasant oral therapies but the improvements and refinements came quickly. Once HAART (highly active anti-retroviral therapy) was identified as the way forward, the race was on to deliver this complex regimen as conveniently as possible.

This was the genesis of Atripla – one pill, once a day, containing an effective trilogy of anti-retroviral drugs. For the HIV+ve person used to popping sometimes dozens of pills per day in complex regimens, Atripla really was a game changer.

Number 2. Keytruda

After my early stint as a GP representative, I spent 18 months as an oncology specialist account manager selling a range of cytotoxins known as vinca alkaloids. In those days, for patients with advanced cancers (of virtually any description) oncologists were trying to eke out a few more weeks or months of life by using highly toxic regimens. But that’s all they had at their disposal. A particularly knotty problem was NSCLC (non-small cell lung cancer), which seemed impervious to any treatment.

If, at the time, you were to present them with the kind of efficacy results delivered by a Keytruda-enhanced chemotherapy regimen, they just wouldn’t have believed it possible.

That’s why it gets my vote, because my personal dealings with oncologists tells me that this was a very high mountain to climb.

Number 1. Humira

Not only a great drug, but a great name. Humira was the first monoclonal antibody blockbuster and thanks to that status, it spawned innumerable MABs and other variations of immunomodulatory drugs. But most importantly, it transformed the lives of patients who hitherto had had little relief from chronic diseases such as RA, Crohn’s and psoriasis. It now has 14 indications, which is a testament to its incredible utility.

So that’s it. Whether you agree with my list or not, these five drugs are exceptional and there are millions of people around the world whose lives have been enhanced and saved by their development. There are so many that nearly made the list, such as Revlimid and Spinraza, but my arbitrary opinion made me reluctantly leave them outside the top five.

Please email me if you would like to discuss this article or propose an alternative ‘Top 5’.