This article provides a definition for investigator initiated research and discusses the role of the MSL in investigator initiated research.
If you read any job description for an MSL role, they will list responsibilities such as;
“facilitation of the investigator sponsored trials process”
“Work as a team to assist in set-up, implementation and execution of company-sponsored local clinical studies”
“Identify clinical and post-marketing study investigators in alignment with Medical Plan”
Therefore, management of investigator initiated research is an important part of the MSL role.
Definition of Investigator Initiated Research
Investigator initiated research refers to a study that is designed and led by an independent investigator, i.e. a KOL who does not work for the pharma company but the study is sponsored or paid for by the pharma company. The funding will be clearly outlined in the publication that arises from the company.
Example of disclaimer on the publication:
· Funding The study is funded by an untied educational grant from [Pharmaceutical Company]. · Disclaimer The funders had no role in the study design, study conduct, analysis or data interpretation. Prior to publication, representatives from [Pharmaceutical Company] had the opportunity to review the manuscript and provide comment on factual inaccuracies, if identified.
What does an MSL do in an investigator initiated trial?
The role of the Medical Science Liaison in managing investigator-initiated studies can be broken down into five steps;
Step 1: Identify Data Gaps
This means to understand what kind of data KOLs would like to see in order to enhance the quality use of medicines. An MSL can identify data gaps by talking to KOLs and simply asking them;
“What do you think the data gaps for this product are?”
The KOL might be interested for example in specific side effects in a certain population, they might be interested in local data, they might be in interested in real world data.
Step 2: Identify Strategic Alignment
When the Medical Science Liaison understands what data gaps the KOLs recognise, the next step is to identify if the data gaps suggested by KOLs, are aligned to the medical strategy of the company.
For example, if a KOL says;
“It would be great to understand the effect of Drug X when added to the competitor Drug Y”
and concomitant use of Drug X and Drug Y is contraindicated and would therefore represent a risk to patient safety, this study is not aligned to the medical strategy and the pharma company would not fund it. Similarly, if the medical strategy wants to demonstrate the efficacy and safety of Drug X, this is best done without it being used in combination with another drug.
For example, if a KOL says;
“it would be great to understand the tolerability in elderly patients”
and one of the core strategic objectives of the company is to highlight the suitability for patients over 65, then an investigator initiated study focused solely on these patients would be strategically aligned.
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Step 3: Identify suitable KOLs
Once the MSL has defined what KOLs want and what the company wants, the next step in managing investigator initiated research is to identify KOLs who have the necessary experience to be lead investigators on the study.
These KOLs must have a lot of experience in designing clinical trials, and also have a certain amount of influence so that when the paper is published people respect the data and know that the study was well designed.
Personally, I have worked with KOLs who don’t have a huge amount of experience designing clinical trials and their lack of experience really showed and created a massive amount of work for the company as we needed to get the protocols reviewed by statisticians and other study design experts to assess he validity of the study ad there was so many changes that needed to be made so it was a hugely resource intensive experience for me as an MSL at that time. On the flip side of that I have worked with KOLs who have lots of experience designing clinical trials and they have been an absolute dream to work with as an MSL, they are so confident and competent when it comes to designing studies and they are very good at designing trials and providing accurate assessments of what is feasible.
As an MSL when identifying suitable KOLs, check their publication history and in particular the publications where they were first and last author.
Step 4: Finalise study proposal
Once the MSL identifies a suitable KOL and discusses their interest in a clinical trial that is strategically aligned, the next step is for the MSL to work with the KOL to finalise the study proposal and get it ready for approval.
The first step in study approval is to get the outline of the study approved. This will simply be a short paragraph detailing the study population, primary and secondary endpoints, type of study and a rough budget and time line required. The MSL will then get initial approval based on this and then can go back to the KOL and ask them to develop a full study proposal. The reason I suggest doing this is to ensure that the KOL doesn’t spend hours and hours on a study proposal that will be rejected as that can be very damaging to the MSL KOL relationship. An MSL should always manage expectations of a KOL in terms of the study being approved and be very transparent about the investigator initiated research approval process.
Step 5: Approval of proposal
The next step once the MSL has the full proposal is to facilitate submission & approval of the study.
The MSL must then work with the internal team (which includes other members of the medical team, and may include members of the marketing, regulatory affairs, clinical teams) to get study approved.
The MSL then develops milestones for the study and liaises with the KOL regarding these milestones and timelines. An example of a is: milestone 1: 50% of patients recruited by the end of Q1 2021. Milestones are really important to keep the study on track.
Once the study has been approved (and there may be some back and forth between the pharma company and the KOL to finalise the study proposal) the next step in IIR management will be the MSL acting as the primary liaison between the company and investigators from inception to publication. This involves the MSL maintaining regular communication with the KOL study lead to ensure the study is on track.
Interpretation of clinical data is a key skill of an MSL and required when reviewing investigator initiated research proposals. Learn how to critically appraise clinical data using our self-paced workshop.
Step 6: Data Dissemination Plan
The MSL will then develop a data dissemination plan. A data dissemination plan details how the study data will be communicated to people. When the study is complete, what conferences will the data be presented at? What journal will it be submitted to? What other KOLs can you share the data with once it is published? Is it possible to submit a poster to a conference ahead of the final results of the study?
A data dissemination plan increases the reach and impact of the data and ensures people are educated on the new data and it’s impact on clinical practice.