Clinical Development

Conducting clinical trials in patients, to gain confidence in safety and efficacy of the treatment in the new indication.

Much of the preparation for the trial can be done in parallel with the non-clinical development phase (if appropriate) to avoid a pause in the programme, though researchers should be mindful of the possible financial risk involved.

The overall aim of this phase is to demonstrate that your repurposed treatment is beneficial in the new patient population. It could be tested alongside other, existing medicines that these patients take and/or alongside a group that receives no treatment. Information from these trials will be used to make a case for your repurposed medicine being prescribed for the new indication.

Usually a novel medicine needs to be tested in a group of healthy volunteers to make sure it is safe at a relevant dose before it is tested in patients. This is called a Phase 1 trial. For a repurposed medicine this may not be necessary because the medicine has already been tested in humans, though you should always seek expert advice. If a trial in healthy volunteers is not needed then you may progress straight to Phase 2, where the repurposed medicine is tested in the new patient group. Information about a safe and effective dose, relevant to the target patient population, should be generated where necessary in addition to existing data.

For repurposing generic medicines one well designed and performed clinical study can sometimes be sufficient. You could consider innovative trial designs to maximise the amount of data generated from a single trial or group of participants

Main activities and considerations:

Trial planning

Clinical Trials Authorisation

  • In order to conduct a clinical trial in the UK you must apply to MHRA for Clinical Trial Authorisation (CTA)
  • Advice can be found on preparation of the CTA documentation¬†on government Clinical trials for medicines webpage
  • Putting together the CTA is a labour intensive and specialised task. If you are working with a Clinical Trials Unit or a Contract Research Organisation (CRO) to run your trial they may be able to undertake this activity, or advise on how to get this completed. Alternatively, it may be necessary to employ a Clinical Trial Manager to lead this stage, or to engage a specialist consultant to put together the documentation. Funders may be able to advise on how to go about getting access to such services.

Evidence gathering and generation

  • What data may be needed to progress to Marketing Authorisation? Visit Beyond Clinical Trials - ''On-label'' or ''off-label'' prescribing for further information
  • CTA approval does not mean that the approved trial will provide the evidence required to support an application for a licence variation.
  • Engagement with the regulator can be important to confirm what evidence is required or desirable. Joint MHRA/NICE advice is available. Visit Resources - MHRA and Resources - NICE for further information.
  • Consider all of the data available, not just trial data, especially if products are already used in your area of interest. The regulators can be pragmatic about the kind of data they see and are open to looking at the totality of the data, including data from other sources, for example published literature.
  • Other useful links:

Funding for the trial

  • Have you secured sufficient funding for the trial?
  • How much post-trial follow-up is needed and how much will the funder support? Will your organisation be able to support follow-up beyond what the funder will support, if required?
  • If a further trial is required afterwards have you investigated possible sources of funding for that follow-on?
  • What will the funder require in the way of reporting?
  • Visit Funding for further information.

Trial design and site

  • Have you identified a site and a Chief Investigator?
  • What infrastructure is available at the trial site to support the trial? For example:
    • Is there a clinical trials office?
    • Is there a pharmacy that can store and dispense the drug appropriately?
  • Who will cost up the trial?
  • Which elements of costs will you be seeking funding for? Which are research costs and which are NHS costs? To define these when applying for funding, you will need to engage with an NIHR AcoRD specialist. You may need to complete a Schedule of Events Cost Attribution Template (SoECAT).
  • Is the trial site and design accessible and appropriate for the patients you are seeking to recruit?
  • How does the trial design fit with the standard care that the target patients receive? For example, can you schedule trial appointments to coincide with standard care visits?
  • How will you design your clinical trial? Are your planned clinical endpoints appropriate to take the programme forward to the next phase?
  • How long will the study take? The longer the study, the higher the chance of patients dropping out. Therefore more patients need to be recruited to ensure the study completes and the statistical power is maintained.
  • Most funders will expect participant numbers and statistical analysis plans to be developed using substantial statistical expertise, and robustly justified.
  • Are there any potential issues with timely recruitment to, or drop-out from, the trial? How could you mitigate for these?
  • A feasibility study is sometimes an excellent way to capture initial information about the study (including recruitment, expected side effects to put in the Investigative Medicinal Product Brochure, et cetera) and can help shape more appropriate clinical endpoints. Participant numbers don't need to be as large for this, but you do need sufficient numbers to be able to make a conclusion.
  • Have you considered, and adequately costed, which sorts of personnel you will need to carry out the trial (for example research nurse, researcher, statistician, database manager)? Consider who will consent the patients, collect the samples and process them.

Running the trial and data capture

  • Have you set up a trial database?
  • Is it properly protected and only accessible to those who need it?
  • Is data captured only on computer, are there paper or electronic Case Report Forms (CRFs) that need to be generated?

Drug product and placebo (if required)

  • Have you secured supply of drug product (and possibly placebo) for the trial? Issues to be considered include:
    • Where will the drug come from? Is there a company that can supply it or can it be purchased through a hospital pharmacy?
    • If being shipped from a manufacturing facility, where will it be stored at the trial site?
    • The drug and placebo (if required) will need to be in matching packaging to allow for blinding. Licenced drugs normally come in popper packs, but placebo does not. Some repackaging may be required. If so, ensure that the supplier has the correct licence and access to repackage, and that the cost of these resources and activities are factored in to your overall trial cost.
    • Will you contract a 'blinding service' to manage the recording of allocation to trial arms?
  • Develop any contracts for these elements carefully. Visit Non-Clinical Development - Contracting with the CRO for general advice.

Next steps

  • Are further trials necessary after the initial trial?
  • How long will the patients be followed up after the trial and have you planned this and secured resource for it?
  • Visit Beyond clinical trials for information on how your treatment may reach patients.
  • Once a phase 2 trial is completed, consider whether to apply to the Medicines Repurposing Programme (England only) for support with further research, licensing, and implementation. Visit Funding - Medicines Repurposing Programme for further information

Paths to patient access?

This is an area that can sometimes be unclear to those embarking on repurposing projects, but is crucial to bring the treatment to the patients who need it. Visit Beyond clinical trials which outlines options and aims to provide some guidance as to how your medicine may reach patients.