Before a new product launches, many manufacturers need to decide if they are going to initiate a Special Access Program (SAP; also referred to as an Early Access Program [EAP] in the US or a Compassionate Use Program [CUP] or Named Patient Program [NPP] in the EU) for their brand while they are going through regulatory approval. The demand for SAPs has risen over the years due to the increased usage of social media outlets and the widespread online access to blogs and clinical trial websites. SAPs offer manufacturers an ethical, compliant, and controlled mechanism to offer patients, who have no other options, access to investigational drugs outside of clinical trials and before commercial launch. In addition, SAPs provide manufacturers with an excellent mechanism to give key opinion leaders, prescribers, regulators, payers, advocacy groups, and patients early exposure to their product and to gather real-world evidence of their product’s efficacy and safety. This could have huge benefits and ramifications for global product market access strategies and future clinical trial and extension studies. The “real-world evidence” collected could, in turn, help regulators and physicians capture positive efficacy signals in patient subpopulations not originally studied.
Advantages of SAPs
Some manufacturers may consider implementing an open-label extension study (OLE) as a bridging strategy to allow patients access to investigational products that are still under regulatory review. However, this can be very time-consuming and expensive to initiate, and most companies do not want data collection to be their primary objective when waiting for approval. In addition, some companies may consider the negative financial implications of having a clinical study open at the time of product launch and the potential impact it could have on initial sales revenues. Some countries may need to initiate an SAP because their product has been approved in another country and there is media attention and additional market “pressure” to make their product available to terminally ill patients. SAPs are an important “stop gap” strategy, especially for HTA countries where the lag time from product approval to reimbursement can be unpredictable and quite lengthy. Finally, SAPs may be the best option for a specific country to employ, especially in instances of rare disease products, when a full regulatory approval and/or reimbursement decision may be unlikely and an actual product launch is not part of that manufacturer’s strategy in that specific country.
Risks of SAPs
Of course, SAPs do not come without their risks. Many manufacturers are concerned about possible adverse events and/or “real-world evidence” that may surface, which could threaten the positioning and fledgling reputation of the product with early users. It could also have long-term negative effects on regulatory approval and reimbursement, market share, adoption, and revenues. Sometimes, the adverse events might be the result of inappropriate use by the prescribers, as they are not governed by an actual trial protocol and cannot be actively managed by the manufacturer, as SAP promotion is illegal. In addition, manufacturers may not have the information required to accurately predict demand, which could affect production planning and result in inadequate supply for the market. Should a company decide not to employ an SAP, they could also run into social media campaigns and patient advocacy group pressures, and be labeled “unethical” in their approach. Lean manufacturers may also have concerns about tying up valuable internal resources, both financial and human, in managing an SAP when ongoing work associated with inline brands or developmental work are in progress.
SAP Decision Criteria
When deciding if an SAP makes sense, approximately 6-12 months prior to a final decision, cross-functional teams should carefully consider the following:
- Where the product is in its clinical development
- Early efficacy and safety data
- Launch dates and timing in other countries
- Regulatory submission dates and anticipated approval dates
- Drug manufacturing and supply chain issues
- Drug labeling issues and packaging requirements
- Number of countries that will be launching, and their proximity, language, access regulations, and size
- Requirements for safety data collection and potential implications
- Internal resources available to manage
The investigational new drug can be made available free of charge to only ex-trial patients or to all patients depending on the market need and the manufacturer’s available resources and drug supply. Some manufacturers will “grandfather” SAP patients once the product is launched and/or reimbursed, and others will create an SAP expiry date and require some or all patients to start paying for drugs upon regulatory approval.
SAP Implementation Protocols
Every country has their own legislation and protocols for initiating and employing SAPs. For example, in Canada, physicians need to request access and are required to complete a Special Access Request form, which is then faxed to Health Canada for screening, review, and approval. In addition, the manufacturer needs to provide authorization to supply. In the US, Expanded Access programs (EAPs) can be initiated by either the manufacturer or physicians, but the criteria to define and select the patient population targeted is set by the manufacturer. Groups of patients or single patients can benefit from the EAP and do not have to pay for the drug, although physicians are often paid for participating in the program. Off label usage is not permitted in EAPs. To access a drug through an EAP, patients need to provide consent and the manufacturer or physician needs to submit an expanded access treatment protocol to an Institutional Review Board, as well as form 1571 or 3926 to the FDA. Finally, the manufacturer needs to provide a Letter of Authorization.
In Europe, a Compassionate Use Program (CUP) can be issued with similar specifications as in the US. However, permission can only be granted to clinics or hospitals, not to individual patients, and physicians do not get paid to participate. The early access to medicine scheme (EAMS), launched in the UK in April 2014, is comprised of 3 key steps:
- Manufacturer must submit Phase I/II data to the Medicines and Healthcare Products Regulatory Agency (MHRA) and apply for a promising innovative medicine (PIM) designation
- Upon receipt of the PIM, the MHRA will review the Phase I/II data
- If the EAMS scientific opinion is positive, the National Health Service will commission the drug
European manufacturers are charged fees at each step but cannot charge for the drug when the CUP is issued. Named Patient Programs (NPP) are unique in Europe, in that:
- Only physicians can initiate
- Only single patients can receive the drug and not groups
- Physicians are held liable instead of the manufacturer
- Physicians are not paid to participate
- Manufacturers can charge for the drugs in this type of program
One of the risks of NPPs for manufacturers is that, although they can generate early revenues, they need to be mindful of their pricing strategies, as often the price set during the NPP can be used as a benchmark at the time of product launch.
Garnering Advice for SAPs
There are many things that need to be considered before launching an SAP program. To help with this process, there are companies that can assist manufacturers with establishing an advisory board platform, leveraging the expertise of select stakeholders, and to give timely and expert advice on the best options to maneuver through the SAP decision-making process. Stakeholders can include payers, regional or national market experts, physicians, allied healthcare providers, wholesalers, intermediaries, private insurance company advisors, pharmacy benefit managers, and patients. Enrolled advisors can be engaged through a series of online touchpoints either in the form of web meetings or online asynchronous assignments. Through these advisor online touchpoints, manufacturers can solicit feedback on their regulatory, market access, and SAP strategies, as well as gain insights on how to navigate their decisions based on anticipated market dynamics, pricing considerations, and present and emerging competition. In addition, manufacturers can leverage virtual working groups to help develop templates for SAP forms; these often require content for clinical rationale, which can then be provided to physicians through educational programs so as to simplify their application process. Finally, virtual advisory boards or working groups can be utilized to bolster the SAP submission dossiers and rebuttals from the regulatory bodies in question.
The virtual nature of suchboards and working groups can help increase the engagement rates of advisors, who are often extremely busy and being utilized by multiple manufacturers for similar purposes. Moreover, the assignments, when carefully designed to be compelling, relevant, and timely, can give the advisors or steering committee members time to pause, reflect, process, and review their colleagues’ comments on their own time, allowing for more thoughtful and granular insights shared through the online forums. When performed in an effective manner, the manufacturer’s workload and cost are minimal a when compared to more traditional in-person consultancy meetings. Virtual advisory boards and working groups are excellent tools for manufacturers who need to weigh all of their options with the varied expertise of their most valued customers when making the strategic decision to move ahead with an SAP.