From clinical trial to available medicine - why does it take so long
How patients are able to access medicines after they’ve been through a clinical trial
More than 20,000 clinical research studies begin each year.1 Previous articles have described how a series of three or more clinical research studies answer questions about the safety of a potential new medicine and how well it works. It often takes as long as 10 years to collect all the information needed from the studies – or even longer if the disease being studied develops very slowly; or if it is difficult to find suitable people to take part.1 Evidence collected in clinical research studies is used to apply for legal approval for the use of new medicines;2 however, legal approval does not necessarily mean the medicine becomes available for doctors to prescribe.
Ensuring medicines are made available at a reasonable cost
Government agencies, healthcare providers and pharmaceutical companies have a shared goal of making safe and effective medicines available to patients who need them as soon as possible. After the legal approval of a new medicine, these organisations work together to understand whether – and in which specific types of patients – the medicine is good value for money. This may include learning more about how the medicine works in the ‘real world’ – i.e. outside the tightly controlled conditions of a clinical research study. Participants taking part in this sort of research may gain personal benefits from accessing approved medicines earlier than they otherwise could.
Most countries have a separate approval step in which the health authorities decide whether they are willing to pay a form of subvention for the new medicine.3,4 The typical length of time between legal approval and the point at which a new medicine becomes available to patients varies from 6 weeks in the United States, to 21 weeks in the United Kingdom and 66 weeks in Italy.5 So what takes so long, and why do some countries take longer than others to make a new medicine available?
Who decides which medicines are made available to patients?
The bodies, known as payors, that pay for prescription medicines vary from country to country. Usually, the cost of medicines is covered by a publicly funded drug plan at national or regional levels, a privately funded drug plan, individual patients, or a combination of these.4Available funding may be limited, for example, by budget allocation or potential impact of the drug plan, so decisions need to be made as to which medicines to fund, often through a process that assesses the added value of a new medicine.
For patients who may benefit from a medicine that is legally approved but not yet available in their country, a few options are available. The possibility for this to occur as well as the different options available will vary from country to country depending on local laws and regulations.
Although the legal approval of a medicine is usually based only on whether it works and is safe, payers are also interested in other information, such as how much additional benefit may be gained from the new medicine compared with the best treatment(s) already available. They want to understand the long-term cost to society, of buying the medicine, compared with potential future cost savings, such as avoiding hospital admissions or reducing the risk of more serious medical conditions. For example, paying the price of the medication may outweigh the cost of having to support a large number of patients through extended periods of hospitalization. It may also be important to learn whether patients outside of a clinical research study have any problems with taking the medicine as instructed. With limited budgets, payors may also consider the value of a medicine for one condition versus another medicine for a different condition, or the overall budget impact of a new medicine. Other factors may include the severity of the condition or unmet need.
The information needed by payors is sometimes, but not always, available from the original clinical research studies.6 Drug manufacturers may also submit economic analyses based on projected costs and benefits. To help collect more information about the costs, risks and benefits of the medicine in a “real-world” healthcare situation for a particular country, a healthcare provider may make the medicine available for a short time (a year or two) while it is studied further – this is sometimes called ‘provisional’ or ‘conditional’ funding.6 As countries have different ways of funding medicines, and different ways of judging value for money, it is usual for medicines to become available to patients at different times.5
Is there a way to access medicines that are legally approved but not yet funded?
For patients who may benefit from a medicine that is legally approved but not yet available in their country, a few options are available. The possibility for this to occur as well as the different options available will vary from country to country depending on local laws and regulations. But below are some indications of how this could work.
- If no other approved treatment seems suitable, a doctor may be able to apply for special funding of the new medicine as a ‘one-off’ case.7,8
- Patients who have previously had successful treatment with a medicine as part of a clinical research study may be allowed to continue to take that medicine until it is available for their doctors to prescribe. However, this is not always the case.9
- Patients may participate in studies known as ‘early access programme’, or ‘post-approval study’, which are different from earlier clinical research because participants will not usually need to undergo any additional medical tests beyond those they would receive as part of their routine medical care. Participants will also know exactly which medicine they are receiving, and that the study medicine has previously been shown to work. These studies are very important because they help researchers to understand how the medicine works for a wide range of people, which may include people with more complex medical needs than those included in the original clinical research studies10
- Because clinical trials are conducted on a selected sample of patients, even after approval, there may be some “uncertainty” as to which patients in the total population will actually benefit. Manufacturers may enter into “managed access/entry agreements” with payers whereby patients who might benefit are provided access through a registry and only those who respond received continued access through the drug plan. Over time, the access criteria will change to reflect learning from the registry.11
- Viergever RF, Keyang Li. Trends in global clinical trial registration: an analysis of numbers of registered clinical trials in different parts of the world from 2004 to 2013. BMJ Open 2015;5:e008932
- How Drugs are Developed and Approved. United States Food and Drug Administration. Available from: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ (Accessed 1 November 2016)
- Saltman D. An Introduction to European Market Access. Seminar Public Health and Primary Care, Imperial College. Available from: https://www1.imperial.ac.uk/resources/7F5B8EAC-E83A-4C71-9192-7BACDFCAFBA7/europeanmafeb27.pdf (Accessed 1 November 2016)
- ISPOR Global Healthcare Systems Road Map, February 2015. Available from: http://www.ispor.org/htaroadmaps/ (Accessed 1 November 2016).
- Mycka J, Dellamano R, Lobb W et al. Regulatory Approval to Patient Access, and Evaluation of EU5 and US National Timing Differences. ISPOR 6th Asia-Pacific Conference September 6-9 2014
- Jarosławski S, Toumi M. Market access agreements for pharmaceuticals in Europe: diversity of approaches and underlying concepts. BMC Health Services Research 2011;11:259
- Individual funding requests - A guide for patients and service users. NHS England, 2015. Available from: https://www.england.nhs.uk/commissioning/wp-content/uploads/sites/12/2015/06/individl-fund-reqts-info-pats.pdf (Accessed 1 November 2016)
- NHS England Cancer Drugs Fund, 2016. Available from: https://www.england.nhs.uk/cancer/cdf/ (Accessed 1 November 2016)
- Cedars-Sinai, 2016. Available from: https://www.cedars-sinai.edu/Patients/Clinical-Trials/Clinical-Trials-Frequently-Asked-Questions.aspx (Accessed 8 December 2016)
- Patil S. Early Access programs: Benefits, challenges, and key considerations for successful implementation; Perspect Clin Res; 2016 Jan-Mar; 7(1):4-8
- Charles River Associates, Managed entry agreements in the context of medicines adaptive pathways to patients Nov 2016, http://adaptsmart.eu/wp-content/uploads/2016/12/CRA-MEA-in-the-context-of-MAPPs-Final-Report-16-December-2016-STC.pdf