Clinical trials now and then: 1983 vs 2014

Clinical 04- MQIn 1983 I administered my first new medicine to a human being in the department of clinical pharmacology at the Wellcome Research laboratories in Beckenham, UK. It was the antiepileptic lamotrigine (Lamictal) and it eventually reached a turnover of more than a billion pounds, but we were not so sure then. Lamotrigine killed dogs (due to a metabolite that we later found was only formed in the dog) and did nasty things to the kidneys of a certain species of rat.  After internal discussion we went ahead anyway probably to the benefit of many patients with epilepsy and depression, who are currently being treated with lamotrigine. This first in human study was also one of the first with an approval of an ethics committee. Before this we just went ahead after approval by one of the directors.

So the study went ahead. My boss came down from a meeting, had an iv cannula inserted and took the first capsule, returned to his meeting and occasionally walked down for an ECG and a blood sample. The second subject was the chemist who invented the molecule and was rather nervous about causing problems for ‘his’ molecule. This almost inevitably induced a nasty migraine attack. “Don’t winge Dave”, we said as he lay there with a bad headache and we injected anti vomiting drugs in him. The rest is history.

This story may cause severe distress in the modern quality assurance officer, trial monitor, or an attentive regulator. However it is real and by describing the past tries to highlight the contrast with the present.

When we started CHDR in 1987 we very quickly started to do studies for industry and our maiden first-in-human study was with an antiarrhythmic that prolonged the QT interval in the ECG. This cost about 80.000 Dutch Guilders and this would be in today’s terms about the same amount in euros. The protocol had 20 pages and the whole submission dossier to the ethics committee about 30.  The study was completed very quickly after the protocol was written and monitoring was done by one of the employees of the company. She visited us once or twice from Belgium and as a rule brought Belgian chocolates.

The real cost of such a study today is a factor 10 higher, the dossier would be about 20 times more pages and the staff involved in such a study is about tenfold. Of course this is excluding the internal cost of the company. Most likely they will employ an IT company for the study database, an ECG company to read the ECG’s, a central lab company to study the clinical chemistry and a monitoring company to meticulously go over all the blood pressures and side effects. Rules against conflict of interest have done away with the Belgian chocolates. Many of this is global so there is quite a CO2 footprint associated with such a study.

Some of this is good and I would not suggest that we go back to the informal studies of the last century. However, we have a duty to keep new medicines affordable to the whole world. The cost of current drug development is without a doubt unsustainable and the efficiency of the process must be increased. Innovating drug development and its methodology can do this. This is what we have been doing at CHDR for the past 27 years. This new blog series will be written by all our staff members and tell you about our views on this innovation and what we do about it. We hope you are going to read them and share your comments.

By: Adam Cohen

4 thoughts on “Clinical trials now and then: 1983 vs 2014

  1. Dear Dr. Cohen – Adam:
    Gefeliciteerd … very interesting recollection of the changing times in medicine-pharma research and how you and your org have evolved to become a leading [world] clinical research entity.

    Many thanks for your advice over the years best regards,

    Fred Foley

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  2. Dear Dr. Cohen – I agree with Fred – a most interesting recollection . I will say however, that most regulations that we now operate under have been enacted due to an abuse of the clinical trial procedures.
    As an example, in the US – investigators must provide documentation regarding their financial interest in a particular drug or sponsor. This requirement came about due to irregularities with a subject who was in a trial and who did not receive optimum care from the PI since the PI was the owner of the drug patent. It was in the PI’s interest to keep the subject on the drug as long as possible. The subject experienced significant ADRs and should have been removed from the study early on. A sad tale – but it does happen.

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  3. You are right but regulations that are retroactive generally are good preventing what happened in the past but no guarantee that something else does not happen in the future. When this invariable does, new regulations are made to prevent that, and eventually one ends up where we are now. The danger sign is when you get experts in regulation. The best approach is to start again with the thought “if we had to regulate trials now what would we do” .Try to read the new CT regulation fro Europe . If you get through the 80 considerations and all the articles try to imagine how anyone could deal with this. Also try to look at the functional design of the new clinical trial submission portal and try to imagine you’d ever want to submit a clinical trial again. The inspiring thought is that as clinical researchers we should regain control. The Dutch word for regulation is ‘ rule giving’ which implies some higher authority giving these ruls to us. I am in favor of ‘rule taking’ where we take control over them.

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  4. ‘IT has happened’ too often. As a business executive I have been engaged to perform a number of business turnaround fixes many with ongoing clinical trials funded by some in the venture capital community. A number were in clinical stage I and II with suspect-troubling outcome results that were kept ongoing for reasons that meant to foster more financial support for the entities and their investigators some had less than ethical result outcome reporting.

    Political issues frequently loom over institutions and can bias reviews unfortunately based on the need for supporting resources controlled by those seeking financial gain at near any cost.

    Having objective unbiased expert ongoing data review by those [e.g.CHDR] not in it for financial gain can be and IMO remains essential both then and of course now to conduct such without bias.

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