Are You Ready for Phase II?

Three signs that you are (and a few that you are not)

You did it. Your compound made it through Phase I. You were finally able to test the compound or IP (Investigational Product) on humans. Now, it’s time to evaluate whether your compound is really good for anything or if it’s just something that seemed to work really well in mice. In order to get the right answer, you must ask the right questions, then develop and execute a strategy that helps you get one step closer to market.

1.  New pathway or me-too?

If your compound is a breakthrough pathway, then the best practice is to study the trial design for the most recent breakthrough compound. Mimic the design of that drug, not those of the me-too. Refrain from setting outlandish or unattainable expectations. Superiority may not be necessary if your compound has advantages, such as dosing (QD vs. BID) or route (SQ vs. IV) biological superiority (humanized vs. chimeric), over the initial breakthrough formulation. Set your primary endpoints similar, if not identical, to those of the pivotal trials of the initial compound. Let the sales and marketing teams differentiate the advantages.

2.  How do I choose my sites?

You need a strategy. You need to be efficient. You need to spend your resources wisely. Here’s why: you will be required to push 250 subjects through your 16-week Phase II or 750 subjects through your parallel Phase III trials.  

The traditional strategy is to cast a wide net and contract with 40 or 50 sites. Those sites include the below-mentioned factories, mills, dabblers, high turnovers, professors, performers and the Dr. PIs. You should be aware of these sites and how they operate; it’s critical to your success.

The Factory/Mill

The factory/mill site will only enroll a small percentage of your subjects due to the physicians’ lack of interest. These sites do not rely on any particular disease state to succeed. The quality of data will be adequate. The volume is hit or miss because these sites often contract with physicians in the community who are not entirely committed to clinical research. In these cases, the doctors are often conducting many trials in many disciplines.

Dabblers

The dabblers are the doctors who may have an interest in research or may see it as another revenue source. You know these site locations, and in most cases, they are not mature sites, but keep your eyes on these dabbler sites. They have the potential for becoming a performer. As you allocate contracts, you may want to give a new site a chance instead of going back to a poorly performing mill/factory.

The Performers

You know these sites, too. They are must-have locations. These are your home run hitters, your playmakers. You will not close enrollment on time without these sites. Thirty-percent of these sites provide 70 percent of the data. Every sponsor in the same space wants their participation and wants them without competitive studies. They are expensive, but worth every penny. Get out your checkbook; it will be the best money you ever spent.

Dr. PIs

Dr. PIs are individuals who would like to be principal investigators and heard they can make money doing clinical research. They also heard that it wasn’t much work. These Dr. PIs give you five minutes of their time at the pre-selection visit and even less time at the site initiation visit. Unfortunately, they always happen to be busy the weekend of the investigators’ meeting. Yet, somehow, these sites made it on to your list of locations to consider. Should you? The answer is a resounding no.

These sites will enroll a subject or two, but the physicians will not know much about the protocol or the subjects. Are they worth it? Again, no. There’s always a chance that one of these PIs could be randomly selected to participate in an FDA audit and who knows what he’ll say to the auditor. This isn’t exactly the person you want speaking about your trial to the governing and regulatory bodies.

The High Turnovers

As the name implies, this is the high turnover site. You’ll know it because the person who filled out the feasibility study is no longer employed there. And, you keep introducing yourself to new people every time you communicate with the site. Beware of this site. There is something systematically wrong with the management, and while enrollment may be satisfactory, the quality may not be acceptable.

The Professors

You must contract with these sites. These are the “names” you need on these trials in order to validate all of the work every other site does. The university medical centers have their own Institutional Review Boards (IRB). Their IRB must review your protocol.
 
The process of contracting the university-based medical center sites is long and painful. And your company will probably pay the highest overhead and cost per subject. The good news is that they routinely have very low enrollment and that also happens to be the bad news. You will not want to work with them, but your board of directors will force you to do so. If one of the “Professor” sites happens to also be a “Performer,” avoid telling anyone in order to minimize competition for these sites.

3.  How many sites do I need?

You need as few as possible. Ten-to-fifteen performers can get you to your enrollment number, especially if the sponsor explains the aggressive strategy. The standard strategy is to align the study with many sites and set low expectations. You will get to your goal with more headaches, sleepless nights, monitoring visits, etc. It will be a lengthy, time-intensive endeavor and the human capital will be great. Also, there is greater potential for add-on sites midstream; however, these will be expensive and time-consuming since they must be brought up to speed.

The Secret Formula

Get all the performers you can. Add in a few dabblers. Use professors sparingly. This formula isn’t intended to save you money. It will, however, economize your investment. You’ll pay performing sites high fees, but it will be worth it. You’ll have fewer headaches and a higher likelihood of being on or ahead of schedule and at market sooner.

Coordinating a clinical trial requires commitment, knowledge, dedication and a stop at nothing mentality. You’ll encounter numerous road blocks along the way, but with practice, patience and persistence, you’ll be able to successfully deliver a drug that could help more than just mice live a healthier life.

Seth B. Forman, M.D., is a principal consultant at Forsight Consulting, principal investigator with Forward Clinical Trials and board-certified dermatologist and founder of Forman Dermatology & Skin Cancer Institute.