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Innovation in clinical trials

Posted by
26 Jul 2016

This blog will look at the future of clinical trials, we’ll run through the current 'phases' of clinical trials, focus on some of the key innovations in trial design and also take a look at the new approach permeating clinical research, ‘precision medicine’.

Current trial design

There are some standard ‘phases’ that trialists currently use to categorise the various stages used to investigate a new therapy. These can be seen below and are generally surmised as Phase 1, Phase II , Phase III and Phase IV (not shown below, but includes longer monitoring trials, investigating long-term environmental interactions).

Early phase trials generally look at whether a drug is safe and what the side effects are. Later phase trials aim to test whether the new treatment is better than the existing standard treatment. As you can see above, the study duration and patient numbers escalate as we move from left to right. Bloodwise funds trials in all three main phases, but in terms of the number of trials, we mainly fund early phase II trials, such as the ones that open across the TAP portfolio. Later phase trials are expensive and our resources are best utilised at swiftly moving promising looking treatments to later stage testing.

A more detailed breakdown of clinical trial phases can be found here, but for now I want to run through some new and exciting approaches to delivering trials. These new designs aim to better investigate rare diseases and accelerate drug testing, whilst at the same time attempting to minimise patient numbers and time taken.

New trial designs

In recent years, the use of adaptive design methods in clinical research has become increasingly popular due to its flexibility and efficiency.  Adaptive designs offer the potential to reduce study duration and patient exposure whilst maximising the probability of a successful outcome. An adaptive design allows modifications to be made to a trial while the trial is still ongoing. The intention to follow an adaptive process is set out in advance, researchers then review trial data in real time and make amendments to improve the accuracy of the research. For example, if one treatment arm (an arm is a group of patients in a trial on one particular treatment) of a three arm trial looks less promising than the others, it's possible to shift patients to arms in which the outcomes appear to be more promising. This approach provides the ability to shift study resources to more successful treatments, thereby providing more statistical evidence to the effects the investigators are really interested in. The Bloodwise funded study LI-1 ‘pick-a-winner’ is a randomised trial investigating a number of different acute myleoid leukaemia (AML) treatments and a good example of this adaptive trial process. Patients on the trial are allocated to 1 of 6 treatment groups and treated with a range of drugs. The trial design is then adapted to select the best performing groups and eventually 'pick a winner' from the range of treatments.

Another recent innovation in clinical trials is the Bucket design. Bucket trials are designed to utilise one particular drug and test that drug against a number of different diseases. The advantage of this approach is that patients with different diseases can be 'pooled' together under one larger trial instead of lots of smaller trials, thereby saving time and resource In a similar approach, Bloodwise funds a number of trials that use drugs originally designed for one disease which have been repurposed to treat another. The Bloodwise funded study TAMARIN is investigating the drug 'tamoxifen', a well known breast cancer drug, in the treatment of Myeloproliferative Neoplasms.

Another problematic area in clinical research is the study of rare disease. Researchers wanting to investigate diseases with small patients groups need to design powerful trials (trials which give a strong probability of the outcome being true). One way to achieve more power is through the Umbrella study design. These types of trials are also called biomarker studies, as patients are grouped according to their genetic biomarkers. Umbrella studies are designed to test the impact of a range of different drugs in a single type of disease (‘under the umbrella of one disease’).


Patients in these studies are selected based on the genetic error prominent in their disease and treated with a number of drugs known to target this specific error. Whilst umbrella studies can be very complicated due to the fact they often involve lots of treatments and delivery methods, they allow researchers to simultaneously test a range of different medicines thereby accelerating the investigative process. This approach can also help to identify patient subgroups who would most benefit from the medicines tested. Bloodwise is helping to develop this strategy by funding a trial of a drug that harnesses the body's own immune system to fight cancer cells. Due to the drug being potentially effective across a range of diseases, the study based in Southampton, will assess the drug's performance in both AML and non-hodgkin's lymphoma (NHL) patients who show a particluar genetic marker.

The video below may help to further explain the different trial designs mentioned above..

Precision medicine in clinical research

Along with these innovations in trial design the advent of precision/personal/stratified medicine is providing lots of new possibilities to better treat patients.  Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. This new approach is about using the appropriate treatment for the appropriate patient at the appropriate time, allowing healthcare professionals to better manage a patient’s illnesses based upon individual characteristics. Precision medicine is an arena pioneered by blood cancer researchers, Joe (Bloodwise Research Officer) has done a more detailed blog on the subject which can be found here

As discussed above, precision medicine strategies are also beginning to be applied to clinical trials. Our own TAP funded BUBBLE trial, which is investigating multiple myeloma (MM), is a great example of this. Advances in our understanding of the biology of MM have shown that patients have varying genetic abnormalities related to the disease. This represents a major challenge in the development of new treatments. Professor Kwee Yong’s research group from University College London have identified a new class of drugs that could play a crucial role in targeting specific high risk sub-types of MM.  This the first trial of its kind to first genetically identify MM patients and then treat accordingly. The success of this approach relies not only on the performance of the drugs but also on robust lab analysis (precision) to select the right patients. 

It's becoming increasingly apparent that a one-size-fits-all paradigm for conventional study design is a thing of the past. Advances in trial design and personalised medicine bring huge opportunities for clinical researchers in haemato-oncology.  Close collaboration between academia, regulatory agencies, pharmaceutical companies and funders - such as Bloodwise - is becoming even more important when considering how best to deliver innovative research and develop new treatments.

Bloodwise continues to be at the forefront of this new and exciting arena, providing the support and framework needed to ensure scientific advances are translated into real benefits for blood cancer patients.

For more information on anything above, please get in touch with Emil.


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