For biotech investors, the news of approval of a new clinical trial by a regulatory body such as the FDA is a genuinely exciting milestone. But what many might not be aware of are the multiple steps involved in actually commencing a trial after the appropriate regulatory agency has given approval.  

This can lead to investor frustration and the misconception that perhaps things aren’t running smoothly when in reality, for complex, multicentre multinational trials to open all sites for enrolment, it can take up to twelve months post-approval. 

Here’s a topline summary of the steps that most biotechs and pharmaceutical companies will need to sequentially work through before recruitment of patients can begin. 

1. Development of core study documents such as final study protocol, Investigator’s Brochure (a collection of clinical and non-clinical data about the investigational product), and Informed Consent Form (a document volunteer signs when they agree to participate in a clinical trial).
2. Selection of a Clinical Research Organisation (CRO), the specialist company that actually runs the clinical trial on behalf of the drug company. This involves several bid defence meetings where quotes are analysed, and contract negotiation. 
3. Clinical research site selection and feasibility (with potential sites often being in multiple countries), followed by site qualification visits at each site where more detailed assessments is conducted about the site personnel/equipment to ensure the site has adequate resources and patient population for successful study execution.
4. Negotiation of budgets at individual study sites 
5. Submission to local Regulatory Affairs (RA) and Ethics Committees (EC). These bodies review research proposals involving human participants to ensure they meet ethical standards and guidelines.
6. Answering questions/requests from RA/EC to obtain approvals. Questions can range from pre-clinical package to risk/benefit assessments and further requests may involve conducting additional experiments.  
7. Submissions to the Research Governance Office (RGO) at each site and further negotiations on study documents, and site budget. The Research Governance Office is the office within the hospital that administers the processes used by the institution to ensure that it is accountable for the research conducted under its auspices. To be properly governed, research must be conducted according to established ethical principles, guidelines for responsible research conduct, relevant legislation and regulations and institutional policy. This step alone can take up to six months. 
8. Preparation of study plans including but not limited to: 
   • IP = Investigational Product manual
   • PVG = Pharmacovigilance plan (how to assess and report serious adverse reactions)
   • MMP = medical monitoring plan (the plan ensuring safety oversight and reviewing the protocol (e.g., study halting rules) and information about the study as it becomes available)
   • Lab manual
   • Clinical monitoring plan
   • Statistical Analyses plan
   • DM = data management plan etc.
9. Build and validate the electronic data capture (EDC) database to be used to record all the data from the subjects in the trial
10. Conduct Site Initiation visits at each site which involves training the site study team on study protocol, adverse event reporting data recording in EDC and other systems to be used during the study. 

As you can see, it’s not a short nor simple process. And, within this process, some of the steps may take multiple iterations even if appropriately undertaken. 

I appreciate that it’s difficult for already patient investors to continue to be patient but at the end of the day, designing good clinical trial strategies to ensure they have the best chance of reaching the intended end point and move to commercialization is imperative.