An organisation may fund research without being the Clinical Sponsor. A Clinical Sponsor is the responsible party for a study or investigation and is per definition defines as;

An individual, company, institution or organization which takes responsibility for the initiation, management and/or financing of a clinical trial,

which includes the responsibility for compliance with all regulations and reporting requirements.

Typically Investigator Initiated Studies are supported by funding from:

1. Own department/university/hospital
2. Governmental agencies, or
3. Third-parties, such as: Foundations (e.g. heart foundations), Non-profit organizations, Charitable boards or Private companies.

The physicians are very likely to conduct Investigator Initiated Studies and these offer to him/her both a better and more independent control of the study and opportunity for publications and public presentations.

From the company side there are several advantages of conducting an Investigator Initiated Study such as:

• No internal resources to manage the study by itself
• Relatively inexpensive way to obtain data on the (new) application of a therapy
• Company ‘scientific’ image
• Interested to support the research of certain groups, but doesn’t want to provide an unrestricted grant/donation

A company may provide research grants to fund legitimate, scientifically sound, clinical and pre-clinical studies and research where such research is either conducted by qualified grant recipients, and is intended to provide valuable scientific and clinical information, improve medical care, lead to promising new treatments, promote better delivery of healthcare, or provide other benefits to patients. It is important to know that research grants may NOT be provided with the intent of impacting SALES numbers. We normally say that as a company, you have to have “hands off” during the set-up, conduction and reporting of the trial.

Typically, these Investigator Initiated Studies have been small-scale, single-center studies providing sufficient data for abstracts and presentations at conferences but are usually not ground-breaking, landmark trials. Lately, this has changed and due to the coming new regulatory landscape in Europe the need for clinical evidence to support company products and their claims has increased dramatically. Therefore we at Qmed see more and more that companies are using funding of Investigator Initiated Studies as a source to develop clinical evidence to support their claims. Also pre-CE mark.

The downside of Investigator Initiated Studies are sometimes that the quality are not always optimal. This is due to several reasons such as:

Application of the therapy

• Physicians (untrained) are using the medical devices inappropriately
• Application to patients/diseases not tested before (off-label use; SAEs !)

Study design

• Too small sample size => risk of false negative findings
• Inappropriate endpoints (e.g. survival when therapy focuses on QoL)
• Wrong comparator, quasi randomization, etc.

Study execution

• Participating centers/investigators
• Progress of the study (delayed results may not be relevant anymore)
• Monitoring, if done at all

Data Analysis & Publications

• Description of device/drug and its indications may contain errors
• Statistical tests may be inappropriate
• Interpretation of the data (statistical significance vs clinical relevance)

Increased funding from governmental sources (e.g. EU) will increase the number of ISS; this will further decrease the influence of companies on what research is done with their products.

Many Investigator Initiated Studies take much more time to start, execute and complete than planned. Physicians typically overestimate 1) how fast they can identify participating centers, 2) enroll eligible patients, and 3) the time they can invest in the execution of the study.

Therefore, if the study is key to the company, do not use the Investigator Initiated Study concept, but become the sponsor of the trial or advice the physician to use a private or academic Clinical Research Organisation (CRO) or ask the CRO to become the Sponsor and manage the study.

Background

Qmed Consulting was asked to help set up and manage an EU clinical study for eighty patients with an irreversible and life-threatening disease. The investigational product was originally approved for a different indication, but as this particular trial proposed a new indication, all regulatory approvals were required in order to start the study.

The Challenge

The principal investigator and Scandinavian-based sponsor of the study had no previous experience setting up European clinical trials and was also facing a heavy workload as director of department in the hospital where he worked.

A number of obstacles were presented in this particular study:

• Diversity of work procedures and limited access to necessary equipment: Countries outside of Scandinavia operate differently than countries within Scandinavia. In terms of clinical practice, this means that not all diagnostic tests are available in all centres.
• Different investigator agreements and additional local agreements: Countries outside of Scandinavia may require a different style of investigator agreement and may also require additional agreements depending on local requirements.
• Varied study insurance requirements: Study insurance is required in countries outside of Scandinavia for investigator-initiated clinical trials.
• Country-specific regulatory submission documents and approvals: Regulatory submissions in countries outside of Scandinavia require documents that are not always present in Scandinavian submissions; therefore additional approvals may be required (e.g. R&D approval in the UK).
• Complexity and volume of study documentation: A large amount of study-specific documentation is required for a clinical trial: protocol, protocol summaries, investigator brochures, patient information and consent forms, patient safety cards, patient diaries, etc.
• Study registration requirements: Each study must be registered within an internationally – recognised clinical trials database (e.g. clinicaltrials.gov).
• Permanent communication factors: Regular communication is required with study centres to collect the necessary documents for regulatory submissions and to organise the onset of the study.
• Database requirements: A database must be created for data management and CRFs must be written for the study.

The Solution

Qmed Consulting was appointed as the CRO for this investigator-initiated study due to their comprehensive clinical research experience, successful track record, accessible Scandinavian-based location, and extensive European network. Qmed Consulting began the project by discussing the study outline with the sponsor and appointing roles and responsibilities. The sponsor admitted that he had a limited amount of time due to his demanding work schedule. A weekly conference call was arranged at the beginning of each week to go through each member’s required action items. A weekly progress report was then sent out by Qmed Consulting at the end of each week to show the progress made.

Qmed Consulting agreed to write as much of the study documentation as possible, giving the sponsor the opportunity to review any documents that he thought necessary. A steering committee was organised to write the protocol and to ensure that a European standpoint was maintained. Qmed Consulting organised the distribution of drafts to the steering committee and followed up with members that had not yet responded.

Qmed Consulting organised the necessary translations for each country involved and liaised with the sites where certain documents had to be modified according to local requirements (e.g. patient information sheets and consent forms).

Much time was spent corresponding with the company that provided the investigational product and funding for the study. This was necessary to collect the specific product documentation required for the regulatory submissions (investigator brochure, product details, etc.). This required constant communication with various departments within the manufacturing company.

Regulatory submissions for the Regulatory Authorities and Ethics Committees were prepared in both English (Regulatory Authority submissions) and local languages (Ethics Committee submissions). This involved creating separate folders that corresponded to the requirements of each regulatory body in each country. Although there are similarities among the documentation, the set-up and presentation of the submissions vary from country to country.

Qmed Consulting organised an investigator meeting so that the sponsor could bring all investigators together to discuss the product and details of the study. The travel arrangements, meeting room, equipment, and presentations were coordinated so that the meeting would run as efficiently as possible.

Qmed Consulting also acted as primary contact for the electronic database team to ensure that the database was constructed in accordance with protocol standards. Qmed Consulting also assisted with the production of edit checks and a help manual.

Conclusion

An investigator-initiated study is challenging for both the investigator and the CRO, as there is no industrial partner to assist with the preparation and review of the long list of required documentation. This particular study presented a fascinating opportunity to set up and run a trial for a very specialized group of patients who have limited treatment options.

By setting up communication channels that were convenient to the sponsor (weekly calls, weekly progress reports, and limited email communication), a close working relationship was established. Qmed Consulting was able to act as a barrier to all unnecessary correspondence and was able to take on the time-consuming administrative duties of the clinical trial.

On account of Qmed Consulting’s highly experienced consultants and their ability to efficiently conduct clinical studies for investigational products, the sponsor was able to:

• Reduce the time and cost to complete the study.
• Achieve clinical study milestones through experience-based organisation and planning.
• Accelerate turnaround of scientific publications and scientific podium presentations.
• Increase efficiency as a result of consultant’s privileged and long-term relationships with hospitals.

This collaboration of medical excellence with industrial experience led to a win-win situation. The sponsor was able to delegate all set-up and maintenance tasks to Qmed Consulting, so that he could focus his expertise on patient care and innovative assessments of new treatments in clinical trials.

To find out more about our full range of Contract Research Organization services, please contact us: www.qmed-consulting.com