Interview with Dr. Ingrid Klingmann on the EU Cross-border Clinical Trials Initiative (EU-X-CT).

1. Dear Ingrid, would you please briefly introduce yourself and the EU-X-CT initiative to our readers? 

My name is Dr Ingrid Klingmann, by profession I am a general practitioner and clinical pharmacologist. The largest part of my life I have spent on making clinical trials work more efficiently and ensuring that the study participants are optimally protected. I am also a founding member and for over 10 years Chairwoman of the European Forum for Good Clinical Practice, EFGCP. This is a not-for-profit organisation enabling multi-national, multi-stakeholder exchange of experience and joint solution finding for problems in the clinical development of new medicines. Since the year 2000, we practice patient engagement as all our Working Parties are co-chaired by a subject matter expert and an experienced patient representative. European initiatives grounded and/or worked out by such collaboration were EUPATI, the European Academy on Therapeutic Innovation, and Good Lay Summary Practice, GLSP, a new European standard for planning, creating, translating and disseminating lay summaries on clinical trial results that makes patient involvement in this process mandatory.  

European health authorities are aware that European patients can only quickly get access to new medicines when these are also developed in Europe which means that clinical trials testing these new medicines are organised in Europe. They even implemented a comprehensive, IT-based clinical trials authorisation system to make clinical trials faster authorised and more reliably supervised. And the new system allows that the information on ongoing clinical trials in the European Union and the summary of their results in lay language are easily available to European patients.   

But Europe has a big problem: we are divided into many countries and therefore patients speak different languages and live in different healthcare systems. They are cared for by national doctors according to national healthcare practices. Clinical trials are organised in a limited number of hospitals because it is important to standardise the study performance as much as possible in order to achieve reliable results. As a growing number of these clinical trials are testing new medicines in rare or life-threatening diseases, patients suffering from such diseases and living in a country where none of these few trial centres are located, have no access to such a potentially life-saving treatment option within their own healthcare system. And the practice has shown that trying to join a clinical trial in another country, in another healthcare system, has many very different kinds of hurdles that in many, if not most, cases cannot be overcome.

It is clear that this situation cannot go on. It is unfair and against all European values. New laws are no option as it takes too long to develop them and a European Union law does not cover all countries in Europe. European organisations have to find their own way to improve the situation. This is why EFGCP and EFPIA, the European Federation of Pharmaceutical Industries and Associations, decided to create EU-X-CT, the EU Cross-border Clinical Trials Initiative. Meanwhile, over 70 patient organisations, academic institutions, pharma companies and multi-stakeholder not-for-profit organisations from over 25 countries in and outside of the EU have joined EU-X-CT. Our aim is to collect and provide as much information as possible about the conditions for patients when they want to join a trial in another country and for investigators when they want to enrol patients from other countries into their clinical trials. And we want to develop recommendations for all involved parties on what can be done to improve the chances for patients in need to join a clinical trial wherever it takes place. 

2. How do you see the current status of cross-border access to clinical trials for European patients? What seems to work well and what still needs to be improved?

The hurdles for patients who want to join a clinical trial in another country are huge. It starts with the fact that many doctors do not know about clinical trial options, think negatively about clinical research or see too many administrative difficulties and therefore do not support patients in their attempt to join a trial in another country. 

Another problem for patients is the language hurdles. Patients need to be able to talk with their study doctor and his or her staff. They need to understand all the organisational details of the trial as well as the potential risks and benefits and they need to be able to talk with their doctor about the treatment effects and possible side effects.  Ethics committees allowing the investigator to perform the clinical trial have often very strict requirements for ensuring that the communication between the investigator and patient works reliably. If such reliable communication is not ensured they don’t allow enrolment of foreign patients.

But even bigger and much more complex are the financial hurdles: the academic or industry sponsor of a clinical trial must cover all trial-related costs. But for a patient from another country, there are more costs:  the travel and accommodation costs to the site at the beginning and during clinical trial participation, but often, the diagnostics and baseline care of a patient with this life-threatening or rare disease need a hospital stay and coverage of such costs are in most countries not clarified. Nobody is responsible and thus the patient has to cover that him/herself. And it is unclear who covers the costs of treatment of a side effect once the patient is back home as insurance conditions do not foresee such a situation. And there are many more practical hurdles that we try to understand in our Initiative country by country.  

And there is no central, freely accessible place where patients, doctors and investigators can find information on national conditions.

In summary, nothing is working well so far but we have highly motivated investigators and patient organisations who work on making it happen on a case-by-case basis and we have a growing number of organisations and competent authorities, ethics committees and insurance companies who are collaborating to make cross-border participation in clinical trials easier for all patients in need.   

3. How can rare disease patients personally get involved to enhance cross-border access to clinical trials in Europe? 

Patients with a rare disease can personally join EU-X-CT either when their patient organisation is a member or completely individually. There are no legal, financial or any other obligations connected to such membership. We just enable a joint platform for all who want to help with as much as they want and can do. Concretely we have prepared questionnaires for patients, investigators, sponsors, ethics committees, regulatory affairs experts and insurance companies to learn about their personal, and national experiences in cross-border trials. These questionnaires are on the EU-X-CT website (https://eu-x-ct.eu/) and can be found under “Support/Join us” (https://eu-x-ct.eu/support-us). We are very grateful for every completed questionnaire even if the respondent can answer only one of the questions in the questionnaire. We collect experience through “patient journeys” that patients who participated in a trial abroad share with us.

4. What changes for the benefit of EU patients do you expect the EU-X-CT initiative could bring in the future? 

Ultimately, we hope that the EU-X-CT website will become the broadly known and used source of practical information for patients, doctors, investigators and sponsors interested in enabling cross-border patient participation in clinical trials. We hope that our recommendations will enable a certain level of harmonisation of requirements and guide all stakeholders involved in improving processes in clinical trials that facilitate such cross-border participation. And we hope that ultimately, national groups will use the available information on national conditions and the motivation that our Initiative has created to work with their national healthcare providers, regulators, ethics committees and payers to clarify and improve the national cross-border trial conditions for their patients with rare and life-threatening diseases.   

5. To conclude, do you have any message to share with the HAE Junior patient community in the Czech Republic?

Every single contribution counts! Please get engaged with us and help to establish a Czech community that works on that topic in the Czech Republic in close collaboration with us. It is worth our efforts. If WE are not jointly doing it, nobody will do it in the foreseeable future.

Ingrid Klingmann is a general practitioner and clinical pharmacologist by profession. She spent the largest part of her life on making clinical trials work more efficiently and ensuring that the study participants are optimally protected. She is also a founding member and since over 10 years Chairwoman of the European Forum for Good Clinical Practice, EFGCP. Ingrid is co-chair of the EU-X-CT initiative which seeks to enable and facilitate cross-border access to clinical trials for patients in Europe and make it easier for clinical investigators to enrol patients from other European countries in their clinical trials. The EU-X-CT summary report for patients is available online here.