ROGER EXPLORES… the evolution of clinical trials (Part Two)

by Roger Wilson

What do all the developments in clinical trials mean for sarcoma patients?[i]

Most clinical trials are Phase I and early Phase 2 studies looking at safety and efficacy of new drugs, often with a biomarker target. Most of these studies are conducted in the USA and often not large enough to require the accrual of many patients from outside the US, although there are several Early Phase centres in Europe.  Pharmaceutical companies are the usual funders and sponsors of these studies. European patients will be recruited in highly specialist centres[iii] where the range and number of patients means that accrual of target numbers can be quite fast. It also means that finding out about such studies if you are not treated at one of these centres can seem impossible.

The larger Phase 3 studies of new drugs outside the USA are even more problematic to find at present. There are very few agents in development for sarcoma, and studies in existing drugs (such as dose adjustment studies) are infrequent. Phase 3 trials are usually randomised and can require several hundreds of patients to compare different treatments. In sarcoma they will often be run in many countries although the range of centres may be quite limited, especially when the population is quite small. Surgical and radiotherapy studies tend to be academically led, thus driven by the interest and enthusiasm of clinical leaders. They are funded by charities or government agencies, the latter often only for national patients. This means they can be more accessible in that country but not available at all elsewhere. To add to the difficulties the national commitment to cancer research varies enormously worldwide.

Until recently the most common multi-national funder across the European area has been the European Organisation for the Research and Treatment of Cancer (EORTC). This is an independent Belgian charity based in the University of Brussels. It fully funds very few studies but has great expertise in bringing together groups of funders to support the studies it plans to carry out. It is very adept at matching clinical trials into EU funded initiatives, and it helps shape initiatives which it knows it can apply to.

EORTC has also been the single most important agent in bringing multi-national studies into the challenge of treating sarcoma.  Its Soft Tissue and Bone Sarcoma Group (STBSG) has been one of the charity’s most active research groups throughout its 50+ years of life, and that continues. Some studies extend beyond Europe, usually with the funding support of a national charity or agency. SPAGN has had representative patients attending STBSG meetings for over 15 years and our voice has contributed to many of its studies.

The need for multi-national commitment to sarcoma research is clear. Resolving this challenge carries with it a background need for scientific capability in those countries getting involved. As more tumour sub-types are defined, biomarkers become critical in determining an individual’s eligibility and in some cases genetic variations (mutations) must be present. These usually need to be defined locally, although centralised review may also help.

But the big challenge is data. Converting the patient experience into data is at the heart of a clinical study.

Underlying everything is the need for high-quality data. People do not intentionally distort data, but mistakes are made when data is entered into systems. Data entered at the point it is first discovered should be the rule. However, if it is being entered from a handwritten form it can be misread, entered into the wrong field, mis-typed and not checked. Applying classifications or any other interpretation of core data required from a reporting form must be undertaken by people qualified and trained to do it. Any data which must be entered several times or re-entered because systems are incompatible is open to errors being created.

Possibly the biggest requirement in data management for clinical trials, comes with data sharing across national borders. Interpretation of the General Data Protection Regulations (GDPR) from the EU does vary but the core of the regulations is quite clear. Sharing data for research is allowed, including going outside the EU, but it does require anything associated with personal information to be handled rigorously. The primary requirement is “prior consent”, the person whose data are involved must “opt in”, usually by signing a consent form prior to the information being gathered in the first place. A person who “opted out” can be asked whether they want to change their mind after 12 months. Personal data can only be shared for research if it is anonymised, with any data which could lead to identification of that patient being eliminated. Usually, a numerical code is applied to each patient which stays with them through the study.

Outside Europe where differing data sharing standards exist, such sharing becomes a negotiation, with for example, EU data providers requiring safeguards which match the GDPR requirements they must observe.[iv]

Data agreements between hospitals in different European jurisdictions, allowing research data to be shared, is becoming increasingly common. EORTC sarcoma clinical studies using EORTC data systems are routinely handled. Scientific studies with direct relationships, such as the Sarcoma Accelerator Consortium involving hospitals in London, Paris and Milan, developed a custom legal agreement which observed GDPR requirements.

The world of sarcoma research has many good scientists and clinical researchers available to run lots of clinical studies. What we are short of are research questions which could answer a clear patient-centred need and which a funder will find attractive to fund in a very competitive world. This definition applies as much to pharmaceutical companies as it does to academic research. The companies have the added pressure of a commercial imperative to address, and that influences which research questions they see as viable for them.

SPAGN is working to convince industry representatives that sarcoma are a viable area for development and marketing of new drugs, while also working with our academic community to encourage research, develop and use new models of study design so that smaller groups of patients can be involved, and explore methods which enable use of ‘real world data’ within research.

 

 

[i] Terms used in this blog are defined in Part One, https://www.sarcoma-patients.org/blog/roger-explores-evolution-of-clinical-trials-part-i/, published 8 October 2026, by Roger Wilson.

[ii] Related reading in Voices of sarcoma: https://www.sarcoma-patients.org/blog/should-i-join-a-clinical-trial, published 20 February 2024, by Denise Reinke.

[iii] Among the leading centres in Europe for Phase1/2 studies are the Royal Marsden Hospital,the Institute of Cancer Research in London and the University of Leuven in Belgium. Specialist centres in France include the Gustave Roussy Institute outside Paris and the Léon Bérard Centre in Lyon. Several universities in Germany within the German Cancer Research Centre (DKFZ) alliance, as well as the Milan University hospitals in northern Italy are also active in sarcoma research..

 [iv] Anyone wanting an easy-to-read guide to GDPR requirements should look at www.usercentrics.com.

 

Credits:  Graphic design by Karl Berger