Clinical Trials and the TMF 101 - Blog 1: Basics of a Clinical Trial

What exactly is a clinical trial?

In one sentence, “A controlled experiment to test the safety and viability of a treatment designed for humans.” Easy right. Basically, what this means is above all else the patient is at the core and any new treatment; be it a drug, a device or anything else the patient safety and well-being should always be what people are thinking about. Now that doesn’t mean that everything needs to be 100% safe without any risk, it is a balance.  

Think about it like this, if you came up with a new ointment that cured a fungal infection, but the side effects were nausea, hair loss, bruising, sores, and sleep problems it would never even be considered because the results don’t justify the means. But these are the side effects for chemotherapy, a treatment that although tough on the body, can have positive long-lasting impact on people’s lives. Everything is a balance, it is never black and white, and that is the first thing I want you to remember. 

So where do clinical trials fit in the wider drug development process? 

It probably doesn’t surprise you to know that Clinical Trials are some of the last things to happen during drug development, again thinking about safety you want to make sure that whatever you are going to put people through is safe and the risks are low or have been dealt with.  

Research and Discovery 

Think of this as the very first step, this is where people come up with ideas. They have a problem or an opportunity and try to come up with a solution. That could mean starting with the disease or condition and trying to come up with something to help or having a treatment for something else and looking at new applications for it. 

Non-Clinical Development 

This stage, sometimes also known as Pre-Clinical is where the idea has been thought through and real testing begins. It is also where animal testing happens. Now no one likes animal testing, but it plays a pivotal role in bringing these life changing treatments and cures to people and although not liked should never be ignored. The key here is safety, we want to make sure that whatever the product is it will be safe when we move into the Clinical stage, patient safety is number one! 

Clinical Development 

This is the one you have all been waiting for and may have even skipped to if you were keen. It is Clinical Development where the clinical trials start and where we see our good friend the TMF, but that is a blog for another day. 

Clinical Development is often split into phases, these phases relate to the size and scope of the trial and can give you a good idea of what progress has been made so far. 

Phase I (Phase One) – This phase is the one we all hear in those teen movies “Dude I got paid 2000 bucks to take this drug and play video games for two weeks”. A Phase I study is designed to aimed to test the safety of a new product in healthy volunteers. Those involved are not the targeted demographic, we want to make sure that low levels of the drug are suitable for healthy volunteers and is often performed at sites where constant monitoring can be performed to keep an eye on the volunteer’s health and well-being. Phase I trials are usually a few dozen volunteers at a single site in a single country. 

Phase II (Phase Two) – It is here that actual patients will usually start trying the new product, we are looking at the efficacy (that is, how well the therapy works against the goals set for it at the beginning of the trial) in actual patients with the actual disease or condition being treated. At this point the focus is on both the safety of the product in those who will actually receive it and reviewing the basic benefits of it. Phase II will be a larger patient volume (around 100 maybe) and could be across multiple sites and maybe a couple of countries. 

Phase III (Phase Three) – These are the big ones; you hear about these when a product is close to being released. It is here where potentially hundreds of patients from all over the world are treated with varying different strengths for example to see which gives the optimal response. If a product gets to Phase III, it is a big deal. Phase III will be the largest patient volume (potentially 100’s) and will spin a large number of sites across the world. 

Getting a product to market isn’t just a simple, three step process, to get a drug to market a sponsor could perform, around three to four Phase I studies, maybe two to three Phase II studies and then an additional four Phase III studies. Some of these could overlap and some could be performed out of sequence. It is going to be different for every product and every sponsor. And to give you an idea of the cost of these,  

The average cost of a trial across all three phases is approximately  

• Phase 1 $4,000,000 
• Phase 2 $13,000,000 
• Phase 3 $20,000,000 

And that’s just the cost of the trial, there is a load more that goes into it with staff and other resources! 

But if all this goes well that’s when you get to make the product available to people and hopefully change some lives for the better. Post-approval, Life-cycle Management & Pharmacovigilance 

So finally, you have done all the testing, you have proved the safety and effectiveness of your treatment and it’s out on the market, you are changing lives and making the world a better place, but you are not done with clinical trials just yet. 

Phase IV (Phase Four) – Now caveat, this is very simplistic, but I have always looked at these products produced by sponsors as treatments and cures. Think of it like this.  

• Treatment, something you may be on for many, many years, or even your whole life (Insulin?) 
• Cure, you take it once or maybe a short round of it and that’s it done 

Even the longest clinical trial may only last a few years, and the actual time a patient is taking the drug or using the device may be just a few months. You can get a lot of data from this and can get insight into the effects it will have on the patients, but it won’t tell the whole story. Phase IV trials look at the long-term effects of treatments that people will take for years to come, they review the impact of that treatment to the patient and help update the long-term side effects and impact on people’s health and well-being. Sponsors and others can also get more insight into how well the treatment is doing out in the real world and can help inform any next steps or changes. 

Closing Remarks 

So, there it is, the entire Clinical Development process in like 1300 words, simple. Obviously, there are entire books and collections of work that go into all this in more detail, but I hope it has given you a bit more of an idea of what is going on and maybe helped answer a few questions you have. In the next epic blog post we are going to take a more focused look at one area of the clinical trial, which is near and dear to my heart, the Trial Master File, or as it is more widely referred to, the TMF. 

Make sure you keep an eye out for that when it drops and please let me know your thoughts on the whole process by getting in touch at rtjones@phlexglobal.com or even just drop me an email if you would like to talk more about anything Clinical Trial and TMF related. We at Phlexglobal are always up for a discussion. 

Take Care 

Rob Jones