Rethinking Pharma Part 2: Why the Clinical Trial Process Must Change

The clinical trial process is a costly and integral part of bringing a drug to market, but does it have to be carried out the way it is currently? Is there a better way?

The process is well known to all of us in the industry, with Phase III being large-scale human trials in patients with the condition the drug is to treat, and then when enough of those respond successfully, it will likely gain approval. The issue here is that the more we understand about how the body works, the more we realize that it is highly likely that many of the patients in the trial are not patients who have the condition.

Flawed assumptions

The assumption that they have the condition has been made based on the diagnosis from their symptoms made by their doctor and referred to the trial - and not with a definitive diagnostic in most cases. This assumption is proving to be flawed in a lot of cases. Many conditions share the same symptoms, and the fact that a large proportion of patients in trials do not respond leads me to suspect that there is more going on here than we know.

It is highly likely that many of the patients enrolled have a molecular pathway of gene expression that is not relevant for the specific drug.

As I mentioned previously in my article about precision medicine, if just any patient with breast cancer had been put in the Herceptin trials, it may not have passed the clinical trials and gained approval, and many patients who have been helped by Herceptin would not have survived. If a percentage of patients do not respond and a percentage do, we should really be looking at that as an indicator that we are not seeing the full picture and doing further investigation between these groups. There could be multiple conditions with similar symptoms but with different underlying pathology, or there could be different gene expression with the different patients. In any case, these results indicate something else is going on that should be investigated, and further molecular and genetic analysis of the two groups should be conducted.

I know what you are thinking. “Who can afford to do that?” True. So, that makes me consider that clinical trials should actually be done earlier in the process and as part of the development of a drug, rather than a ‘tacked on at the end for approval’ process. Think of the gains that could be made in advancing the drugs and pinpointing with precision the patients it can help – like Herceptin.

But – here’s the rub.

Due to the enormous costs of clinical trials, in order to reduce this cost, when CROs sprang up (e.g. Covance, Parexel, etc.), pharma companies jumped on the opportunity to change this cost from a constant burden to a variable outsourced cost. It made sense at the time.

Weaving trials into development

If companies could weave trials into development more to incorporate this, they would be far more successful in their efficacy results and outcomes for patients - and profits".

However, if one was using clinical trials effectively and integrating them into the development process, companies that outsource these activities would be unable to do this effectively. If your goal in an initial trial is to understand the biomarker subtypes in these patients and pair them with a diagnostic to work with the drug, then the final approval clinical trial process would require significantly less patients, take a maximum of 2 years and cost considerably less. If companies could weave trials into development more to incorporate this, they would be far more successful in their efficacy results and outcomes for patients - and profits.

In addition to the clinical trial cost savings, we would also see serious cost savings from reduced lawsuits. Constantly in the US you see television ads of lawyers scouting for a class action lawsuit against drug companies. You know the sort of thing: “Have you taken drug x and experienced side effects? If so, call this number 1-800-sue-pharma”. The threat of these lawsuits ensures that clinical trials today go on and on so that the company can ensure all the side-effects are noted and can, therefore, avoid a costly lawsuit.

Bringing down costs

By using the trial for research we may see increased costs to begin with (as you would with a diagnostic), but by looking at the bigger picture, we would see advantages in both costs of clinical trials decreasing by requiring significantly smaller numbers of patients and reduced duration in years to conduct them. As always, Herceptin – and Gleevec – are great examples of smaller, faster clinical trials as the underlying gene expression was identified and utilized properly, which made the clinical trials more efficient.

Some companies are doing some interesting things in this arena – e.g. Novartis and Roche. Novartis have segmented their R&D into divisions based on molecular pathways rather than the traditional body part/system or symptomatically defined disease. By matching the accurately defined disease (by molecular pathway and gene expression) to the development of the drug, we will see highly efficacious drugs with minimal side-effects and safety issues as well as faster, smaller trials and fewer lawsuits. And on top of that, by understanding these molecular pathways more precisely, we may well be able to resurrect many drugs that initially were shown to be efficacious but failed to prove themselves with large trial populations. We can understand the groups that they did work well in, and why, and they then could be re-trialed with the right target patients to allow success.

Enhance success

The clinical trial process as it stands now is a lengthy, costly, inefficient process. In order to understand the condition that our drugs are designed to treat at a molecular and genetic level, we should be utilizing clinical trials more as part of the research process, rather than a tack on at the end to ensure approval.

By doing this we will not only gain both valuable efficacy results and outcomes for patients, but will also reduce clinical trial length and cost significantly, as well as increase our ease of market access and enhance our drug’s sales success and our overall financial results.

If you have any questions, please contact the author, Dr Andree Bates, at Eularis:

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