Beyond Achondroplasia

Growing together with Clara

The ECRAN/ECRIN meeting


The ECRAN/ECRIN meeting was very enlightening.

I meet new people, from all over Europe, USA and Canada and heard their experience, knowledge and concerns about clinical trials. The presentations were pleasant, but others were quite disturbing, because many questions around scientific publications, clinical studies and clinical trials were undercover.





So, what is a clinical trial (CT)?

I know that for the great majority of people, this is an abstract theme, but here you can find some clear ideas.

One point that was well focused during the meeting was the importance of the research teams that get funding for their research and to implement a CT in the best country/place possible, with the best conditions reunited (usually, more patients electable) and best infrastructures, and not in their one country just because it their country. Researchers may think globally too.

One largely mentioned and discussed theme were all the significant problems that reduce the quality and significance of the clinical trial. The most common is designated by Bias.

And what is bias, after all?

Bias is a general statistic term meaning a systematic (not random) deviation from the true value. A bias of a measurement or a sampling procedure may pose a more serious problem for researcher than random errors because it cannot be reduced by mere increase in sample size and averaging the outcomes. (source:

In this site, at (a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals) I found many information related to several topics discussed in the meeting, such as:

Bias in research: the rule rather than the exception?

“There are several ways to produce bias:

1-      Bias through ignorance

2-      Bias by design

3-      Bias by misrepresentation – researchers are an inherently optimistic group the “glass half full” is more likely brimming with champagne than tape water.

Witness the heralding of the completion of the Human Genome Project or the advent of gene therapy, stem cells, antisense, RNAi, any “-omics”-all destided to have a major impact on eradicating disease in the near-term. This tendency for over-statement and over-simplification carries through to publications. The urge and rush to be first to publish a new “high-profile” finding can result in “sloppy science, but more significantly can be the result of a strong bias.

A recent evaluation of 160 meta-analyses involving animal studies covering sex neurologic conditions, most of which were reported to show statistically significant benefits of an intervention, found that the “success rate” was too large to be true and that only 8 of the 160 could be supported, leading to the conclusion that reporting bias was the key factor.

With an increase in bias, data manipulation and fraud, the role of the journal editor has become more challenging, both from a perspective and with regards to avoiding peer-review bias.”


Another question that was discussed was the necessity of providing to patients the full protocol and design of the study, randomization, dosing, blinding and endpoints. And that all trial must be registered before study can begin, and, at the conclusion of the study, every patient has to be accounted for and included in the analysis.

An importante reading is about meta-analysis, mentioned several times during the meeting.


This topic raised in me the question: “Where is BMN-111 protocol? What is the design of this trial? I still didn´t read about it.

All the changes during the trial, the inconsiderate points, that at the end can produce a false result, many times get published in scientific journals.

I confess that during the second day of the meeting, I was shocked by the numbers I heard about reports of trials with masked results. It seemed that the scientific community can be, many times, playing with numbers, in a kind of Russian roulette, just to publish before others. Even if the results are not that trusted. The patient may get more harm that good of some products even not being mentioned by the scientific team responsible for the trial.

Is mandatory for patients organization /patients advocates to ensure that they confirm the existence of the trial registration (this way, it is official and controlled by health independent organizations) and we must know the design and protocol of the trial. It will most certainly reveal to a patient if the trial is good for him or not.

Many reports have lousy data and still are published. It´s crucial to stop all the futility that exists among trials and disclosure all the hidden interests far beyond the interest of the patients.

This was a meeting more directed for large-scale diseases and even so, one of the problems referred was the sample size (number of people enrolled in the trial) and how it can affect the results is a more positive, that might not translate the reality, inflating the good results and power of treatment. So in many cases, the clinical trial team chose small sample size to have a  bigger effect.

So I had/have another enormous question:

So what about a rare disease like achondroplasia? BioMarin has such a small sample size for this clinical trial that, right now, that might put in jeopardize the quality of the phase II results. Lets see the results they bring at the end of phase II.

During the second day, there were four interesting roundtables, and I joined the one about patients advocates. I realised that organisations of non rare diseases can have a large number of clinical trials at the same time, and the organisation can provide contact between the pharmaceuticals involved in the trials and the patients.

In rare diseases, the perspective is far from this one.

ImageOverall, it was a great experience. And Luxembourg is stunning!


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