How managed access, expanded access and clinical trials differ in purpose, legal basis, eligibility, data collection and cost, and how to choose a pathway.
Clinical trials exist to generate evidence for authorisation; managed access and expanded access programmes exist to treat patients who cannot wait for authorisation and cannot join a trial. The three pathways differ in purpose, legal basis, eligibility, oversight, data collection and who pays. The right choice depends on the patient's eligibility, the medicine's stage of development and the rules of the country where the patient is treated.
Patients facing life-threatening conditions often cannot wait for a medicine to complete its full regulatory review. For these individuals, the distinction between managed access, expanded access and clinical trials is not academic: whether an expanded access programme or a clinical trial is open to them decides how, and whether, they can be treated. Each pathway serves a fundamentally different purpose, operates under different regulatory frameworks and places different responsibilities on physicians, sponsors and patients alike. Understanding the key differences between these programmes is essential for anyone involved in pharmaceutical development, clinical practice or patient advocacy. The terminology itself can be a source of confusion, with terms like compassionate use, early access programmes and expanded access clinical trials used interchangeably across jurisdictions, despite carrying distinct legal and operational meanings (Iudicello et al., 2016). This guide clarifies each pathway, its structural requirements and the practical considerations that determine which route best serves patients with unmet medical needs. It belongs to our series on managed access and early access.
Clinical trials exist to generate evidence. Access programmes exist to deliver treatment.
The most fundamental distinction among these pathways lies in their primary intent. While overlap occurs, particularly in expanded access clinical trial designs that collect real-world data alongside treatment delivery, the core objective shapes every aspect of how each pathway is designed, regulated and funded. The EMA's guideline on compassionate use states the line directly: although safety data may be collected during compassionate use programmes, such programmes "cannot replace clinical trials for investigational purposes" (European Medicines Agency, 2007).
Clinical trials are prospective research studies designed to evaluate the safety, efficacy and dosing of investigational therapies under controlled conditions. The WHO describes them as research that "studies new tests and treatments and evaluates their effects on human health outcomes" (World Health Organization, n.d.), and Article 2 of Regulation (EU) No 536/2014 defines a clinical study as an investigation in humans with the objective of ascertaining the safety or efficacy of medicinal products (Regulation (EU) No 536/2014, Art. 2). Their purpose is to produce the data that regulatory agencies such as the FDA, EMA and MHRA require before granting marketing authorisation: clinical trials are the basis for marketing authorisation (Jarow et al., 2017). Participants are selected according to strict inclusion and exclusion criteria, and the trial protocol dictates every element of treatment delivery, from dosing schedules to monitoring intervals.
Randomisation, blinding and placebo controls are common features. These methodological safeguards ensure that the resulting data meets the evidentiary standards necessary for regulatory review. Participants in clinical trials receive the investigational product as part of the research, and their treatment follows the study's scientific objectives. Informed consent documents make this distinction explicit, and ethics committees scrutinise trial designs to ensure that the balance between risk and scientific value remains appropriate.
Expanded access programmes, sometimes called compassionate use programmes, exist for a different reason entirely. They provide investigational drugs to patients with a serious or immediately life-threatening condition who have no comparable or satisfactory alternative therapy and who do not qualify for enrolment in ongoing clinical trials (U.S. Food and Drug Administration, 2026a). The primary objective is treatment: making a medicine that is not yet authorised available to a patient in medical need.
Managed access programmes share this treatment-first orientation but typically operate under a more structured commercial or pre-commercial framework. These programmes are often established by pharmaceutical companies to provide early access to a medicine that has received a conditional approval or is nearing the end of its regulatory review; early access programmes generally cover the period before marketing authorisation and can extend to the period before price and reimbursement approval (Tarantola et al., 2023). The distinction matters because a managed access agreement, the payer arrangement that often accompanies such programmes, frequently includes negotiated pricing, reimbursement terms or outcomes-based contracts with healthcare systems (Dabbous et al., 2020), whereas expanded access tends to operate on a case-by-case or cohort basis without formal commercial infrastructure.
Which route applies, and what it requires, changes at every border. Ideogen maps that for a specific medicine in a specific market, across Europe, MENA, CIS and 94 markets worldwide, in orphan and rare disease. Talk with our experts to see how to bridge market access to cater unmet needs in orphan and rare disease at [email protected].
For the definitions behind these terms, start with what a managed access programme is.
Terminology in this space is notoriously inconsistent. The same programme may be called compassionate use in one country and expanded access in another, and the legal implications of each term can differ significantly depending on the regulatory jurisdiction; the lack of a common definition has even led to access programmes being registered as clinical trials (Iudicello et al., 2016).
Compassionate use originated as an informal mechanism through which physicians could request unapproved drugs for critically ill patients. In the United States, the FDA formalised this process under 21 CFR part 312, creating individual patient, intermediate-size and treatment IND categories (21 C.F.R. part 312, subpart I; U.S. Food and Drug Administration, 2026a); its regulations first described a pathway for access to unapproved drugs in 1987 and were revised in 2009 (Jarow et al., 2017). In the EU, the European Medicines Agency works within the framework of Article 83 of Regulation (EC) No 726/2004, which allows member states to make unauthorised medicinal products available to groups of patients, and its Committee for Medicinal Products for Human Use (CHMP) issues opinions and guidance on how the article is used (European Medicines Agency, 2007; Regulation (EC) No 726/2004).
Over time, the informal nature of compassionate use has given way to structured expanded access programmes with defined regulatory requirements, reporting obligations and sponsor responsibilities. The shift from ad hoc compassionate use to formal expanded access reflects a broader recognition that patient access to investigational therapies requires governance, not just goodwill. Regulators now publish detailed guidance on how sponsors and physicians should establish and manage these programmes: the FDA's questions-and-answers guidance on expanded access, most recently revised in April 2026 (U.S. Food and Drug Administration, 2026b), the CHMP guideline on compassionate use under Article 83 (European Medicines Agency, 2007) and the MHRA's overview of the Early Access to Medicines Scheme (Medicines and Healthcare products Regulatory Agency, 2026a).
The terms managed access and early access programme are used most frequently in European and UK contexts. The UK's Early Access to Medicines Scheme (EAMS), for instance, aims to give patients with life-threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorisation when there is a clear unmet medical need, on the basis of a scientific opinion from the MHRA, and it still runs (Medicines and Healthcare products Regulatory Agency, 2026a); the Innovative Licensing and Access Pathway (ILAP), which the MHRA runs with partners including NICE and the Scottish Medicines Consortium, is a separate pathway (Medicines and Healthcare products Regulatory Agency, 2026b). Managed access agreements, by contrast, are often tied to conditional reimbursement decisions by health technology assessment bodies. In England, when NICE recommends a medicine with managed access, NHS England and the company develop a managed access agreement: a time-limited agreement that sets the conditions for NHS funding and how data will be collected to address uncertainties in the clinical or cost-effectiveness evidence (National Institute for Health and Care Excellence, n.d.). In Scotland, the Scottish Medicines Consortium can accept some medicines on an interim basis, subject to reassessment once further evidence is available (Scottish Medicines Consortium, n.d.).
A managed access agreement is typically a structured arrangement between a pharmaceutical company and a payer or healthcare system, specifying the conditions under which a medicine will be provided, the data that will be collected and the criteria for continued access. NICE's agreements, for example, combine a data collection agreement, which lasts for the shortest time needed to resolve the uncertainties and at most five years, with a commercial access agreement between NHS England and the company (National Institute for Health and Care Excellence, n.d.). An early access programme, while similar in intent, may not carry the same commercial or reimbursement structure: compassionate use is usually covered by pharmaceutical companies, while other early access programmes are reimbursed by third-party payers (Tarantola et al., 2023). The distinction between a managed access agreement and compassionate use is therefore partly one of commercial maturity: a managed access agreement applies once a medicine has a marketing authorisation, because NICE publishes guidance for medicines licensed by the MHRA, and it formalises the relationship with payers while the remaining evidence is collected (National Institute for Health and Care Excellence, n.d.).
For how supply works country by country, read about named patient supply in Europe.
Beyond intent and terminology, these pathways differ substantially in how they are designed, who participates and what role the treating physician plays.
Clinical trials have the narrowest eligibility criteria, set by the protocol. Expanded access is for patients who have no comparable or satisfactory alternative therapy and cannot join a trial, where a sponsor agrees to supply, and managed access agreements may add criteria set by the reimbursement agreement.
Clinical trials impose the most restrictive eligibility criteria. Patients must meet specific diagnostic, demographic and clinical benchmarks, and those with comorbidities, prior treatments or organ dysfunction are frequently excluded. These restrictions serve the scientific integrity of the trial but can leave the most vulnerable patients without access.
Expanded access programmes are generally more inclusive, though they are not without barriers. Sponsors must agree to provide the drug, the treating physician must submit an application (which in the US requires an IND filing) and the patient must have no comparable or satisfactory alternative therapy (21 C.F.R. § 312.305; Jarow et al., 2017); for an individual patient, the FDA must also determine that the patient cannot obtain the drug under another IND or protocol (21 C.F.R. § 312.310). Managed access agreements may impose their own eligibility criteria tied to the conditions of the reimbursement agreement, such as disease severity thresholds or biomarker requirements; NICE's data collection agreements, for instance, define the patient population eligible for the medicine (National Institute for Health and Care Excellence, n.d.). The enrolment process for each pathway reflects its underlying purpose: data integrity for trials, medical need for expanded access and negotiated value for managed access agreements.
In a clinical trial, the physician works as an investigator within the sponsor's protocol. In expanded access and managed access programmes, the treating physician identifies the patient, confirms that no satisfactory alternative exists, requests the medicine from the sponsor and often monitors the patient and reports adverse events.
In a standard clinical trial, the principal investigator operates within a rigid protocol. The sponsor designs the study, the contract research organisation manages operations, and the investigator follows predefined procedures; in the EU, the sponsor and the investigator must ensure that the trial follows the protocol and the principles of good clinical practice (Regulation (EU) No 536/2014, Art. 47). The physician's clinical judgement is constrained by the protocol's requirements.
In expanded access and managed access programmes, the treating physician assumes a far more central role. The physician identifies the patient, determines that no satisfactory alternatives exist, initiates the request to the sponsor and often bears responsibility for monitoring the patient and reporting adverse events. In US expanded access, a licensed physician who submits an individual patient IND becomes a sponsor-investigator, with the responsibilities of both roles (21 C.F.R. § 312.305). In expanded access clinical trials, a hybrid model that combines treatment delivery with structured data collection, the physician functions simultaneously as a clinician and a contributor to the evidence base. This dual role demands both clinical expertise and familiarity with regulatory reporting requirements, which can be a significant burden for physicians outside of academic medical centres.
Regulatory expectations vary dramatically across these pathways, and the intensity of oversight correlates directly with the programme's proximity to formal research.
Clinical trials operate under the most rigorous regulatory oversight. Good Clinical Practice (GCP) guidelines, institutional review board (IRB) or ethics committee approval and detailed statistical analysis plans govern every aspect of trial conduct; EU law also requires sponsors and investigators to take appropriate account of the ICH guidelines on good clinical practice (Regulation (EU) No 536/2014, Art. 47). Deviations from the protocol are documented, investigated and reported to regulators.
Expanded access programmes require regulatory authorisation but operate with considerably more flexibility. The FDA requires an IND application or a protocol amendment for expanded access, and the sponsor and investigator responsibilities that apply to trials apply only to the extent they are relevant to the expanded access use (21 C.F.R. § 312.305). In the EU, a member state that makes a medicine available under Article 83 must notify the EMA, and the CHMP may then adopt an opinion on the conditions of use (European Medicines Agency, 2007); the Clinical Trials Regulation governs clinical trials (Regulation (EU) No 536/2014, Art. 1), while compassionate use is governed by Article 83 and by national law (European Medicines Agency, 2007). Managed access agreements may involve additional oversight from health technology assessment bodies, particularly when real-world data collection is a condition of the reimbursement agreement: under NICE's managed access, oversight groups meet regularly to check the quality and quantity of the data (National Institute for Health and Care Excellence, n.d.). The regulatory burden, in each case, is proportional to the programme's objectives.
All three pathways require safety monitoring, but the scope and purpose of that monitoring differ. Clinical trials collect safety data as part of a controlled research design, with predefined endpoints and systematic adverse event reporting. In US expanded access, sponsors must submit IND safety reports and, when the IND or protocol continues for a year or longer, annual reports; physicians report adverse drug events to the sponsor; and at the end of an individual patient's treatment, the physician or sponsor sends the FDA a written summary of the results, including adverse effects (21 C.F.R. §§ 312.305, 312.310). The data collection is still less structured than in a trial and is not designed to support efficacy conclusions: safety data may be collected, but such programmes cannot replace clinical trials for investigational purposes (European Medicines Agency, 2007).
Managed access agreements occupy an interesting middle ground. Because they often include outcomes-based terms agreed with payers (Dabbous et al., 2020), they may require systematic collection of real-world evidence, including treatment outcomes, quality-of-life measures and healthcare resource use. This data serves a commercial and reimbursement purpose rather than a purely scientific one, but it can contribute meaningfully to the broader evidence base for a therapy. The generation of real-world evidence through managed access agreements has become increasingly important as health systems demand post-authorisation data to inform long-term reimbursement decisions; NICE, for example, uses the evidence collected during managed access to assess whether the medicine should be made available for routine use (National Institute for Health and Care Excellence, n.d.).
Who pays depends on the pathway. In clinical trials the sponsor usually pays for the investigational product and the study procedures; in expanded access the sponsor supplies free of charge or recovers costs where the rules allow; and in managed access agreements the price, and any refund, is negotiated with the payer.
The financial architecture of each pathway is one of its most consequential differences. In clinical trials, the sponsor typically bears the cost of the investigational product, study-related procedures and monitoring. Patients generally do not pay for the experimental therapy: in the EU, the costs of investigational medicinal products and of the procedures the protocol specifically requires are not borne by the participant unless national law provides otherwise (Regulation (EU) No 536/2014, Art. 92), though standard-of-care costs may still be billed to insurers, depending on the health system.
Expanded access introduces more complexity. Under US regulations, a sponsor needs the FDA's prior written authorisation to charge for an investigational drug (21 C.F.R. § 312.8). For an individual patient, it may recover only the direct costs of making the drug available, such as manufacturing or acquiring it, shipping and handling; for intermediate-size populations and treatment protocols, it may also recover the costs of monitoring, of complying with IND reporting requirements and other administrative costs directly associated with the expanded access (21 C.F.R. § 312.8). Many sponsors choose to provide the drug at no cost, though this is not a regulatory requirement; compassionate use in Europe is usually covered by pharmaceutical companies (Tarantola et al., 2023), and compassionate use programmes generally provide unlicensed medicines free of charge (Aliu et al., 2022). The treating institution may absorb the costs of administration, monitoring and adverse event management, which can create financial strain, particularly for smaller healthcare facilities, and in Europe the reimbursement of named patient supply is often unregulated (Rosenberg et al., 2025).
Managed access agreements are the most commercially structured of the three. Because these agreements often operate in the period between conditional approval and full reimbursement, they frequently involve negotiated pricing agreements, risk-sharing arrangements or outcomes-based contracts; in Europe, such managed entry agreements are mostly finance-based, and performance-based agreements, including coverage with evidence development, are used less because of their complexity and burden (Dabbous et al., 2020). The pharmaceutical company may agree to provide the medicine at a reduced price or to refund costs if predefined clinical outcomes are not achieved. This model aligns the financial interests of sponsors, payers and patients, but it requires sophisticated data infrastructure and contractual frameworks that are not necessary in traditional expanded access or clinical trial settings. In England, two dedicated funds pay for medicines in managed access, NHS England's Cancer Drugs Fund and Innovative Medicines Fund, each with an annual budget of £340 million (National Institute for Health and Care Excellence, n.d.).
Often in everyday use, but not in law. In the US, expanded access is the FDA's term for access to an investigational medicine outside clinical trials. In the EU, compassionate use under Article 83 of Regulation (EC) No 726/2004 means making a medicine available to a group of patients with a chronically or seriously debilitating or life-threatening disease who cannot be treated satisfactorily with an authorised medicine (Regulation (EC) No 726/2004; U.S. Food and Drug Administration, 2026a).
The treating physician identifies the option and initiates the request; the sponsor decides whether to supply; the national rules set the route and the documents (European Medicines Agency, 2007; Jarow et al., 2017).
No. Access programmes treat patients who cannot join a trial; they collect safety data but are not designed to prove efficacy (European Medicines Agency, 2007).
The choice among these pathways is rarely straightforward. For patients who meet eligibility criteria and can access a trial site, clinical trial enrolment offers the highest level of oversight and the potential to contribute to the evidence that will make a therapy available to future patients; both FDA authors and the EMA guideline treat a trial as the first option whenever possible (European Medicines Agency, 2007; Jarow et al., 2017). For those who cannot participate in trials, expanded access provides a route to treatment, though it requires a willing sponsor and a physician prepared to manage the regulatory and clinical responsibilities involved (Jarow et al., 2017).
Managed access programmes represent a distinct option for therapies that are close to or have received conditional authorisation, particularly in healthcare systems where reimbursement decisions lag behind regulatory approvals: across European countries, the median time to availability of new medicines was 532 days, ranging from 56 days in Germany to 1,201 days in Romania (European Federation of Pharmaceutical Industries and Associations, 2026). The differences between these programmes, spanning their objectives, regulatory requirements, eligibility criteria and financial models, determine which pathway is most appropriate for a given patient, therapy and healthcare context.
For pharmaceutical companies, the decision to establish an expanded access programme versus a managed access agreement depends on the medicine's stage of development, the regulatory environment and the commercial strategy; for the sponsor's side of that decision, see planning an expanded access programme. For physicians, the critical question is simpler but no less consequential: which pathway, if any, allows this patient to be treated with a medicine that is not yet authorised, lawfully and under the right oversight? Answering that question requires a clear understanding of how managed access, expanded access and clinical trials differ in both design and purpose, and a willingness to act promptly when a patient has no other option.
Ideogen works on the question this article sets out: which pathway, in which market, for which patient. We assess the regulatory route, the supply model and the local requirements across Europe, MENA, CIS and 94 markets worldwide, with a focus on orphan and rare disease, where the unmet need is greatest and the time a patient can wait is shortest. If you are working out how to bridge access for a medicine, write to [email protected].
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