MAPs were once an afterthought for sponsors. However, with clinical trial globalisation, improved communication between trial stakeholders, and availability of information, clinical trial sponsors and drug developers started to realise the benefits of introducing MAPs into their development plans.
According to a data analysis by Clinical Trials Arena, there was an increase in registered Expanded Access clinical trial protocols, a type of MAPs, during the Covid-19 pandemic in the US, but their occurrence has dropped sharply since.
MAP is an overarching term for a variety of regulatory mechanisms, such as the Expanded Access, Named Patient, and Compassionate Use programmes, with a primary objective to make an investigational treatment available to patients before its marketing approval. This gives patients who have exhausted all their options or who do not have access to appropriate trials in their country another chance of finding a potential treatment or cure.
The way that the programme is run solely depends on its geographical location. Requirements from regulatory agencies vary in each country, as some regulators only allow approved drugs in MAPs and sponsors in some areas are required to continue giving access to medication to trial participants after the study is over.
This approach was often misconstrued by the industry as another way of conducting a clinical trial. However, there are key differences between clinical trials and MAPs. For example, MAPs may not have strict inclusion or exclusion criteria, they can involve passive recruitment, and their drug supply is imported into a country on a cohort or individual patient basis.
Additionally, there are several logistical and regulatory stipulations sponsors need to consider before introducing MAPs into their business. Clinical Trials Arena spoke with MAP experts on the sidelines of the Clinical Trial Supply Europe 2023 conference on 15–16 March.
New versus established footprint
Sponsors should start thinking about MAPs when they are setting out commercial plans, says Antonela Mangiaterra, associate director of clinical trial supplies and logistics at Parexel. She explains that there is a link between MAPs and clinical trials as sponsors might want to start the programme in the same place where they are planning to launch the product.
In areas that a sponsor already knows, they have a relationship with sites and healthcare professionals (HCPs), and have established logistical pathways into the country, notes Margaret Radford, unlicensed medicine service manager at Almac. This is especially important if the drug is complex and requires knowledge of how to administer it. However, exploring new territories means significantly increasing their footprint, she adds.
Sponsors also need to consider whether they want to offer MAPs for post-trial participants or new patients. Radford explains that it is a business and an ethical question, especially if a patient is no longer deemed “useful” for the trial but their chronic disease benefited from the drug. In some cases, sponsors already make commitments to continue access for trial participants as part of the trial protocol.
In countries like Brazil, if a drug fails a trial but the participant is deemed by a physician to have benefited from the treatment, sponsors must provide the drug until the patient gets no more benefits, Radford adds. Sponsors need to have an exit strategy and understand the implications of pursuing a MAP in each country, she notes.
Global regulatory challenges
MAPs also have added regulatory complexity as every country has its own requirements. In the US, the 21st Century Cures Act requires pharma companies to have public and readily available information on how they evaluate and respond to requests. However, many US-based companies appear not to comply with visibility requirements, according to a Clinical Trials Arena analysis.
Europe is a challenging regulatory environment to navigate, Radford explains. While the EMA provides recommendations, they are not a legal framework. She notes that the while the framework defines both Names Patient and Compassionate Use programmes, each Member State has its own national legislation on how these will be implemented.
A unified European MAP approach would be welcomed by the industry, but it is not likely to happen because each regulatory agency has its own requirements, says Mangiaterra. She adds that it would make sense to have an approach to MAPs that is similar to how the EMA released the new Clinical Trial Regulation, if possible. “That will improve the implementation and make it easier for regulators and everybody involved in MAPs,” she notes.
This also affects how the drug is labelled. The biggest challenge for sponsors is to understand that the drug is not a clinical trial supply anymore, Radford notes. “Just because the label was fine for the last three years in a country, now you are changing the route of access, which may require a label change,” she explains. Labelling requirements vary in every country. While some EU countries will accept clinical trial material, others will have specific requirements.
Improving communication with technology
For MAPs to succeed, sponsors need to communicate with every stakeholder involved in the programme. “It is important to avoid working in silos in MAPs as it is in standard clinical trials,” notes Mangiaterra.
Sometimes HCPs are expected to review importation documents or invoices and confirm acceptability as an importer of record, which are out of the scope of their day-to-day business. In some cases, there can also be a language barrier, so sponsors and their vendor partners need to provide needed support. Also, sponsors need to set out clear expectations regarding the collection of real-world data. “They might be thinking just about treating one patient and not reporting on a weekly basis to the sponsor,” Radford says.
Communication between different vendors is also crucial. Mangiaterra explains that each vendor will have their own procedures and systems, but if they are not working together with the sponsor, they will not be able to succeed in delivering what the sponsor needs. “For example, how will a supply vendor set up a strategy if they do not know when the end of treatment for a patient in a clinical trial is, [and] who is then moving into a MAP?” she notes.
As such, technology can play a big part in having open communication channels and setting out expectations. Parexel offers its clients a MyAccessPrograms platform, which gives sponsors support on patient identification, physician enrolment, communication, and drug supply management. Also, it has a library with all the information that physicians will need to comply with, Mangiaterra says. Similar technology approaches will improve the implementation of MAPs, she adds.
Is it all worth it?
While it might seem like committing to a MAP is a path with many challenges in sight, such a move still has positive aspects. Radford explains that MAPs can offer commercial benefits. “If you are a company that champions patients, you will get a lot of traction from patient advocacy groups,” she adds. Also, sponsors could have a much bigger patient demographic and country footprint than what was required for their traditional clinical trial.
There is also a corporate social responsibility, as MAPs are bridging the gap for patients who do not have other options, Radford notes. Mangiaterra suggests putting oneself into the shoes of someone with a rare disease who lives in a country that does not have alternative treatments or suitable trials. “You could get a drug that is being tested in another part of the world and you can take that as your last chance of hope,” she adds.
Clinical research and commercialisation are long processes, and they do not cover all patients who may need that solution today. “At the end of the multiple steps of regulatory compliance, importation, and labelling, there is a patient waiting for their last treatment option. This is a key message to keep in our mind when things are complicated,” Mangiaterra notes.
- Sponsors need to consider whether they want to launch their MAP in countries where they have already conducted a trial or explore new locations. Known areas already have an established relationships with HCPs and logistical pathways, but new countries can significantly expand their footprint.
- While the US requires pharma companies to have a position on offering MAPs, each Member State in the EU has different requirements and rules. A unified European approach would be welcomed, but is likely not possible.
- Sponsors need to have good communication with different stakeholders, such as HCPs and vendors. This can be facilitated with technology platforms that would offer guidance for sponsors and other people involved in MAPs.