Selecting a comparator drug is a pivotal part of any clinical trial design. It will have a significant impact on virtually all aspects of the study, but perhaps most importantly, the validity of your outcomes.  

In the early stages of planning, an initial list is likely drawn up, which includes all potential comparators. These will be commercially licensed drugs that are regarded as the current standard for the target indication. The list may be long as there is not always one standout candidate, and other considerations will come into play, such as the similarities to the IMP, comparable dosing, input from KOLs, contraindications, and so on. But there are also a multitude of ‘commercial’ factors that need to be considered, which is where your vendor should be helping. The ideal comparator candidate, from a clinical perspective, may not even be commercially available/accessible, which is something anyone involved in the study design would need to know as early as possible.  

Here, we delve into some of these reasons, hoping to provide clinical teams with signposts to making a viable comparator selection.  

1. Is it even on the market yet?

As a comparator supplier, we are frequently asked to supply the very latest drug to the market. So new, in fact, that they haven’t even been launched yet.  

When a commercial drug is granted a license by a governing body (FDA, EMA, etc.), it is often several months or more before the drug is on shelves and available to purchase. If your study is starting imminently and timelines cannot be pushed, then supplying a drug that has only so far been mentioned in press releases is not viable. Our attention needs to turn to more known quantities – drugs that are already marketed.  

2. The comparator drug we want is marketed, but is it ‘available’?

Not all commercial supply chains are created equal. Some drugs are regularly in and out of stock, some manufacturers choose to strictly protect their assets and only distribute them through secure ‘direct to hospital’ or ‘direct to patient’ channels, and some manufacturers simply do not want to supply their drugs to a study for a new drug that is likely to compete for future market share (contrary to some regulatory frameworks).  

Your comparator vendor should have very quick and detailed insight into the viability of each drug on your initial comparator list, and they should provide that guidance free of charge. If drug ‘X’ is continually out of stock and is hard to access when it is in stock, then it isn’t a robust choice for a large-scale study, so let’s move our focus to drug ‘Y’.  

3. What do all these comparators cost?

As average global drug prices continue to increase, the cost of supplying comparators to clinical trials becomes more and more of a factor. Even the largest sponsors can wince at the cost of supplying a comparator for a Global Phase III.  

Assuming all other factors are equal, then your comparator provider can provide an easy cost comparison for the target candidates, and this can be factored into the decision-making process.  

Beyond that simple comparison, a proactive vendor should be giving guidance on the longer-term outlook for your comparator coming off patent. If you have a 4-year study using a branded comparator, but said comparator runs out of patent protection after year 1, then with proper planning, you could benefit from the final 2-3 years of your study being supplied with a generic or biosimilar version. At the very least, this would provide you with multiple backup options in the event of a shortage. In the best case, it could provide a very significantly reduced spend.  

4. I’d like to use a biosimilar, but which one?

Biosimilars have had the great benefit of reducing the cost of comparators for many gold-standard drugs. There are often many biosimilars of the same drug, which is what creates competition for market share and, in turn, drives down prices. However, where there are many options, there is often complexity and confusion.  

Your vendor should have good insight into key biosimilars in the market. They should be able to tell you which manufacturers are the easiest to partner with for supply, who has the best pricing and the most reliable supply chains, and which biosimilar is licensed in most global markets. That last point is key, as there will be fewer regulatory hurdles and less paperwork if you’re centrally sourcing a biosimilar that is licensed in all the intended trial countries.  

5. I need to manufacture a placebo of my comparator, does that impact my choice?

Your comparator vendor may not be able to make you a placebo, but their input can still help.  

Many drugs are manufactured in multiple presentations: vials, PFS, PFP, etc. A vial is invariably an easier proposition when manufacturing a placebo. There are less detailed components that, when compared to a pre-filled pen/pre-filled syringe that will bring down the lead time, cost and complexity of your placebo manufacture.  

Lean on your vendor to show you the most suitable presentations of comparator if you’re running a placebo study. 

Summary

Comparator selection needs input from a number of stakeholders, and the decision-making is most often driven by clinical personnel. Whilst your comparator vendor can only provide the pieces to part of the puzzle, when that vendor is collaborative, proactive and experienced, the insight can be invaluable. When the sponsor/vendor partnership starts prior to study design, then sponsors can save time, save money and improve outcomes.  

Midwinter Solutions can help and would be delighted to discuss your study plans.

To download a PDF copy of this white paper, please click here.