How Clinical Trials Give Patients a Direct Path to New Treatment Options

Introduction

Historically, fewer than 5% of adult cancer patients in the United States were estimated to participate in clinical trials ^[3]. Set alongside that figure is another: in 2023, the FDA's Center for Drug Evaluation and Research approved 55 novel drugs, of which 28, or 51%, received orphan-drug designation for rare diseases or conditions ^[1]. The gap between trial availability and the patients who could benefit from trials is not an abstract regulatory concern. For patients with advanced disease, exhausted approved alternatives, or conditions affecting small populations, a well-matched clinical trial may be the only treatment option that exists.

That framing deserves a qualification. Investigational products or uses have not yet been approved for the specific context in which they are being studied. Some trials evaluate entirely new products; others study approved therapies in new indications, combinations, doses, populations, or treatment settings. In either case, trial participation can expose patients to additional or different uncertainty compared with standard care. Some participants receive no meaningful benefit; others experience unexpected harms. The regulatory and ethical architecture around clinical trials, from ICH guidelines to IRB oversight to informed consent, exists to manage that uncertainty. What trials provide is not a guarantee of benefit. It is access to a product or use that would otherwise be unavailable in that context, under conditions designed to protect the participant and generate reliable evidence.

This article examines how trials function as a pathway to new treatment options, what expedited regulatory programs do and do not guarantee for patients, how expanded access operates outside formal enrollment, where geography and protocol design create barriers, and what regulatory frameworks now require sponsors to address.

Why Clinical Trials Matter as a Treatment Pathway

ClinicalTrials.gov recorded 455,437 registered clinical trials as of June 2023, of which 64,979 were actively recruiting participants, according to data published by the U.S. National Library of Medicine ^[2]. The volume of active trials means that patients with serious conditions may have studies relevant to their disease running somewhere in the world. The harder question is whether those patients can find and access those studies before other options close.

For many participants, the answer to that question determines whether they have a treatment option at all. Clinical trials are not only a mechanism for generating drug approval data. For patients with rare cancers, late-stage malignancies, or conditions where existing therapies have failed, enrollment may provide protocol-governed access to an investigational product or use that is unavailable, unsuitable, or not routinely accessible outside the study. That access depends on study design, however; participants assigned to a comparator, standard-of-care, or placebo group receive the control treatment rather than the investigational therapy. That potential treatment access is one reason the FDA's expanded access framework, discussed below, exists as a separate pathway for patients who cannot enter an enrolled trial.

The numbers on the other side of this equation are difficult. According to industry-cited figures reported by ACRP in 2024, 85% of trials fail to recruit enough patients, and 80% experience delays driven in part by participant dropouts ^[4]. Each month a trial misses its enrollment target is a month that potentially beneficial therapies remain inaccessible to patients who cannot wait. The operational access problem and the patient treatment access problem are, at their root, the same problem.

The Evidence Base: Approval Pathways and Access Programs

Expedited Approval Pathways and Their Impact on Patient Access

The standard drug development process, which can take a decade or more from discovery to approval ^[27], was never compatible with the urgency of serious disease. Both the FDA and the EMA have created programs to reduce that timeline for therapies addressing unmet medical needs.

The FDA's Breakthrough Therapy Designation (BTD), established under the FDA Safety and Innovation Act of 2012, applies when preliminary clinical evidence suggests that a drug may offer substantial improvement over existing therapies for a serious condition. According to FDA CDER data through September 2024, the Center for Drug Evaluation and Research had received 1,321 BTD requests and granted 538, a rate of approximately 41%. CBER maintains a separate BTD program for biologics ^[5]. A peer-reviewed analysis by Miller, Stern, Kearsley, and Kao, published in Health Affairs in 2024, found that BTD reduces late-stage clinical development time by an estimated 30% compared with non-designated drugs ^[6]. A study published in Clinical Cancer Research in 2023, comparing drugs approved for non-small cell lung cancer with and without BTD between January 2013 and October 2021, found that BTD drugs reduced the risk of death by a median of 31%, against 15% for drugs that never received the designation, and reduced disease progression by a median of 48% versus 41.9% respectively ^[7]. These are not marginal differences.

The EMA's PRIME (PRIority MEdicines) scheme, launched in March 2016, serves a parallel function in Europe ^[8]. PRIME provides early and enhanced scientific and regulatory support to sponsors developing medicines for unmet medical needs, with the goal of shortening development timelines and enabling patients to benefit from new treatments sooner. It offers an early appointment of a dedicated CHMP or CAT rapporteur, as applicable, priority access to scientific advice, and eligibility for accelerated assessment at marketing authorization. According to cumulative data published by the EMA, PRIME applications have been granted eligibility at a rate of approximately 26% across all requests received since launch ^[9]. Neither BTD nor PRIME guarantees approval. A drug can lose its BTD designation if later trial data fail to replicate early efficacy signals, and PRIME designation does not automatically confer accelerated assessment. What both programs provide is earlier, more intensive regulatory dialogue during development, intended to help sponsors identify potential design issues earlier in development before they become pivotal-trial flaws that require major amendments or delay patient access.

Expanded Access: Treatment Outside Enrolled Trials

Not all patients who need an investigational treatment can enter an enrolled clinical trial. Eligibility criteria, geographic constraints, and limited trial capacity each create exclusions. For patients who have exhausted approved options, the FDA's Expanded Access (EA) program, sometimes called compassionate use, provides a separate pathway.

As defined by FDA, expanded access is available to patients with a serious or life-threatening disease or condition when no comparable or satisfactory alternative therapy is available ^[11]. According to the FDA's own Expanded Access Program Report and published data on the FDA.gov physician guidance page, FDA allows more than 99% of single patient expanded access requests to proceed ^[10]. Three categories exist under the EA framework for drugs and biologics: access for individual patients including emergency use, access for intermediate-size patient populations, and widespread treatment use under a large-population protocol ^[11]. For emergency requests, FDA has reported completing its review in less than 24 hours, with treatment permitted before receipt of the written IND submission. For non-emergency single-patient requests, treatment may proceed 30 days after FDA receives the application, or earlier if FDA notifies the physician to proceed. CDER has reported a median actual review time of 4 days for non-emergency single-patient requests ^[10]; this figure is documented in a peer-reviewed analysis by Jarow and colleagues from CDER ^[25].

Expanded access is not an alternative to trial participation. FDA's guidance explicitly states that investigational products should be used in clinical trials whenever possible ^[11]. What EA programs provide is a safety valve: regulated access for patients who have no other option and no eligible trial. Expanded access should not be confused with Right to Try, which allows terminally ill patients to request investigational products directly from manufacturers without FDA review, but does not require manufacturers to provide the product and does not create the IRB oversight structure that governs expanded access ^[26].

Operational and Practical Implications

Where Eligible Patients Never Reach Trials

The structural geography of clinical research is a persistent access barrier. Research reported in the AACR Cancer Progress Report 2024 found that approximately 85% of US cancer patients receive their care at community hospitals and clinics, not at the academic centers where most clinical trials are conducted ^[16]. Only 42.4% of US counties have any clinical trial site at all ^[15]. For patients in the remaining counties, trial participation requires travel that many cannot arrange or afford, particularly among older adults, rural populations, and those managing significant disease burden.

Racial and ethnic disparities compound the geographic problem. Among oncology trials evaluating treatment modalities between 2017 and 2022, only 4.4% of enrolled patients were Black and 4.2% were of Hispanic or Latinx origins ^[15]. A review of FDA drug approvals between 2008 and 2013 found that approximately one in five drugs demonstrated differences in pharmacokinetic exposure or clinical response across racial and ethnic groups ^[14]. Where trial participants do not reflect the demographics of the patient populations who will eventually use a drug, the resulting evidence base for safety and efficacy in underrepresented groups is structurally limited. This is not a theoretical concern about generalizability. It is a direct gap in the evidence produced by trials that systematically exclude large portions of the intended treatment population.

In a 2011 finding from the Tufts Center for the Study of Drug Development, two-thirds of investigative sites failed to meet the patient enrollment requirements for a given clinical trial ^[12]. These figures reflect the same geographic concentration: most large-scale trials are run at academic centers that are not geographically accessible to most patients. The operational enrollment shortfall and the patient access shortfall are two descriptions of the same structural failure.

Protocol Design, Eligibility Criteria, and Patient Access

Clinical trial eligibility criteria govern who can participate. They serve essential purposes: protecting participant safety, preventing confounding, and aligning the study population with the intended drug indication. At the same time, criteria that are more restrictive than the supporting evidence warrants reduce the eligible patient pool and can systematically exclude underrepresented populations. Overly prescriptive exclusion criteria have been documented as a significant contributor to enrollment shortfalls in many trials ^[28].

Protocol quality also shapes patient access at a secondary level. Protocols with internal inconsistencies, poorly defined eligibility thresholds, or ambiguous procedures can generate amendments during the trial period. Tufts Center for the Study of Drug Development benchmark data found that 76% of Phase I-IV protocols required at least one amendment, and protocols with a substantial amendment took an average of three unplanned additional months to complete compared with unamended protocols; many amendments also triggered informed consent changes ^[29]. Each of these downstream effects reduces access, either by delaying trial completion or by introducing friction for participants who are already in the study.

For rare diseases, an additional design challenge applies. Standard eligibility criteria based on clinical disease classification often produce patient populations too small to power a randomized controlled trial. Basket trial designs, which group patients across disease types based on a shared molecular target rather than traditional diagnostic categories, offer a path around that limitation. A 2023 analysis by Zanello, Garrido-Estepa, and colleagues from the International Rare Diseases Research Consortium, published in EMBO Molecular Medicine, found that grouping rare disease patients by shared molecular etiology can substantially increase the number of patients gaining access to clinical trials, and that basket trials based on shared molecular targets have been accepted by regulatory agencies as a basis for drug approvals ^[22].

Regulatory and Documentation Considerations

ICH E8(R1): Patient Involvement as a Design Requirement

ICH E8(R1), the revised guideline on General Considerations for Clinical Studies, was finalized by the ICH Assembly in October 2021 and subsequently implemented by FDA and EMA ^[18]. The revision introduced quality-by-design approaches to clinical study planning, with a central emphasis on identifying what is critical to study quality before the trial begins. Among its stated principles, ICH E8(R1) explicitly addresses patient involvement: the guideline states that involving patients early in study design is likely to increase trust in the study, make recruitment easier, and promote adherence ^[23]. This is a regulatory statement with direct operational consequences.

Sponsors who do not engage patient populations in early protocol development face a higher risk of eligibility criteria that do not match the lived experience of the disease, informed consent documents written above the reading level of the patients who need to sign them, and endpoints that fail to capture what patients would consider meaningful benefit. Each of these misalignments is correctable after the fact through protocol amendments. ICH E8(R1) makes the case, in regulatory language, for building patient relevance into the design before the trial starts rather than adjusting for it afterward.

FDA's September 2024 Guidance on Decentralized Clinical Trial Elements

In September 2024, the FDA finalized guidance titled "Conducting Clinical Trials with Decentralized Elements," following a draft guidance issued in May 2023 ^[13]. The final guidance provides a regulatory framework for trials in which some or all activities take place outside traditional clinical sites, including participant homes, local clinics, and telehealth platforms. The guidance makes clear that decentralized elements do not reduce regulatory requirements for data integrity, participant safety, or investigator oversight ^[13]. The title itself, moving from the draft's terminology of "decentralized clinical trials" to "clinical trials with decentralized elements," signals a deliberate integration of these approaches into existing trial design rather than classification as a separate trial type.

Practically, decentralized elements allow sponsors to recruit from patient populations beyond the geographic reach of an academic research center. This is not a complete solution to the access problem. Reliable internet connectivity, digital device availability, and telehealth infrastructure are not uniformly distributed across the populations currently underrepresented in trials. But decentralized trial design represents one of the more direct regulatory responses to geographic enrollment access challenges, and the only one FDA has addressed through dedicated final guidance to date.

FDORA and Diversity Action Plans

The Food and Drug Omnibus Reform Act of 2022 (FDORA) amended the Federal Food, Drug, and Cosmetic Act to require sponsors conducting Phase 3 studies of drugs, biologics, and certain devices to submit Diversity Action Plans (DAPs) ^[17]. DAPs must document enrollment goals by sex, age, race, and ethnicity, informed by the actual prevalence and incidence of the disease in those demographic groups. The requirement creates a documented accountability structure: the enrollment goals sponsors commit to at protocol submission can be compared against actual enrollment data.

The regulatory status of the DAP framework has been in active flux. FDA released draft guidance in June 2024 detailing DAP format and content; as draft guidance, it is non-binding and represents FDA's current thinking rather than final regulatory requirements. That draft was removed from the FDA website in January 2025 following executive orders from the new administration. The guidance was restored by a court order issued by the U.S. District Court for the District of Columbia on February 11, 2025, and the FDA.gov guidance page now states that the site has been restored to its version as of January 29, 2025 ^[17]. As of June 2026, the underlying statutory requirement under FDORA remains in effect. Sponsors conducting new qualifying Phase 3 studies should treat DAP planning as a protocol development task, not a post-enrollment reporting exercise.

AI and Automation Perspective

Patient pre-screening is one of the highest-friction steps between an eligible patient and trial enrollment. Manual chart review is labor-intensive and inconsistent across sites. Coordinators at high-volume sites can spend considerable time identifying patients who turn out to be ineligible, while patients who do qualify go unenrolled because no one reviewed their record at the right moment.

AI tools applied to electronic health records address this specific bottleneck. A pilot implementation study published in JCO Precision Oncology by Kehl and colleagues found that an AI system applied to treatment-change predictions in EHR data could identify clinical trial candidates at a scale and speed that manual chart review does not support ^[19]. A study published in the AMIA Annual Symposium Proceedings by Dolin, Arafat, Heale, Shenvi, and Chamala evaluated the use of HL7 FHIR Genomics and Clinical Quality Language for automated trial matching, particularly for complex molecular eligibility criteria, and found that FHIR-based standards can represent even multi-part molecular criteria in computable form, making EHR-integrated eligibility assessment technically feasible ^[20]. Research published in Nature Communications in 2024 by Jin and colleagues developed and validated a large language model-based pipeline for matching patients to trials using longitudinal EHR records, demonstrating patient-level matching performance above the criterion-level accuracy of earlier automated approaches ^[24].

These tools do not replace clinical judgment. Eligibility determination requires contextual clinical understanding that automated systems can miss, particularly in cases involving complex comorbidity profiles, ambiguous diagnostic histories, or prior therapy regimens that do not map cleanly to protocol exclusion criteria. The appropriate model is AI-assisted pre-screening that narrows the candidate pool and surfaces likely matches for trained coordinators to review, not autonomous enrollment decision-making.

Implementation in a regulated environment requires additional considerations. Validated performance on internal training datasets may not generalize across institutions with different EHR structures or documentation practices. Prospective validation, documentation of system limitations, and defined human oversight at the enrollment decision point are requirements, not options, for any AI-assisted screening workflow deployed in a GCP setting.

How Kitsa Fits Into This Problem

A persistent bottleneck in getting eligible patients into trials is the time and manual effort required to identify them before formal screening begins. Kitsa's KScreener is designed to use FHIR-connected EHR workflows to pre-screen patients against trial eligibility criteria, with the aim of reducing manual coordinator burden and shortening patient-identification workflows. On the protocol and documentation side, Kitsa's KScribe addresses the quality of the documents that govern eligibility in the first place. Precisely defined, evidence-grounded eligibility criteria can support more consistent screening decisions across sites. Informed consent forms written at an accessible reading level, with plain-language explanations of what participation involves, can support comprehension and informed decision-making. Both product areas address access failures that originate upstream, in document construction, rather than at the point of enrollment.

Key Takeaways

• Clinical trials serve as a direct treatment pathway for patients with serious diseases. For many patients with rare conditions, late-stage disease, or no approved alternatives, a well-matched trial may be the primary treatment option available. Investigational therapy also carries real risks, and enrollment is not a guarantee of benefit.
• The FDA approved 55 novel drugs in 2023, of which 28 (51%) received orphan-drug designation for rare diseases or conditions ^[1]. In 2024, CDER approved 50 novel drugs, spanning oncology, rare diseases, neurology, and infectious disease ^[21]. Each approval was supported by clinical evidence reviewed through an NDA or BLA; although the applicable statutory standards differ by product type, clinical trial participation is a direct upstream contributor to treatment availability.
• Expedited regulatory designations have demonstrated measurable patient impact. BTD reduces late-stage development time by an estimated 30% ^[6]. In NSCLC specifically, BTD drugs reduced death risk by a median of 31% versus 15% for non-BTD drugs ^[7]. EMA PRIME granted eligibility to approximately 26% of applications since its 2016 launch ^[8],[9].
• Expanded Access programs provide a regulated pathway for patients who cannot enter an enrolled trial. FDA allows more than 99% of single patient EA requests to proceed. For emergency requests, review is typically completed within a day ^[10].
• Geographic and demographic barriers remain structural. Only 42.4% of US counties have any trial site; 85% of US cancer patients receive care at community settings where trials are rarely conducted; racial and ethnic minorities remain substantially underrepresented relative to disease burden ^[15],[16].
• FDA's September 2024 final guidance on decentralized trial elements establishes the regulatory basis for conducting trial activities at participants' homes and local clinics, directly addressing a primary structural barrier to geographic access ^[13].
• Protocol quality shapes patient access downstream. ICH E8(R1)'s quality-by-design framework calls for patient involvement in study design as a core principle, not an optional engagement activity. Protocols built without patient input are more likely to produce criteria that exclude the people they were intended to study ^[18],[23].

Frequently Asked Questions

References

1. [1]U.S. Food and Drug Administration, CDER. FDA Approves Many New Drugs in 2023 that Will Benefit Patients and Consumers. FDA Voices, 2024. https://www.fda.gov/news-events/fda-voices/fda-approves-many-new-drugs-2023-will-benefit-patients-and-consumers
2. [2]ClinicalTrials.gov, U.S. National Library of Medicine, NIH. Trends, Charts, and Maps. Data as of June 13, 2023. https://clinicaltrials.gov/about-site/trends-charts
3. [3]Unger JM, Hershman DL, Fleury ME, Vaidya R. Association of Patient Comorbid Conditions With Cancer Clinical Trial Participation. JAMA Oncology. 2019;5(3):431-438. https://pubmed.ncbi.nlm.nih.gov/30629092/
4. [4]ACRP. Enhancement, Efficiency, Equity, and Engagement: Four Trends Shaping Clinical Trials in 2024. ACRP, January 2024. https://acrpnet.org/2024/01/03/enhancement-efficiency-equity-and-engagement-four-trends-shaping-clinical-trials-in-2024
5. [5]U.S. Food and Drug Administration, CDER. CDER Breakthrough Therapy Designation Requests Received by Fiscal Year. Data through September 30, 2024. https://www.fda.gov/media/95292/download
6. [6]Miller KL, Stern AD, Kearsley A, Kao J. FDA Breakthrough Therapy Designation Reduced Late-Stage Drug Development Time. Health Affairs. 2024;43(7):1003-1010. https://pmc.ncbi.nlm.nih.gov/articles/PMC12758617/
7. [7]Aggarwal C, et al. Breakthrough Therapy Designation Criteria Identify Drugs that Improve Clinical Outcomes for Patients. Clinical Cancer Research. 2023;29(13):2371-2377. https://pmc.ncbi.nlm.nih.gov/articles/PMC10324637/
8. [8]European Medicines Agency. Launch of PRIME: Paving the Way for Promising Medicines for Patients. EMA, March 2016. https://www.ema.europa.eu/en/news/launch-prime-paving-way-promising-medicines-patients
9. [9]European Medicines Agency. PRIME: Priority Medicines. EMA cumulative key figures, updated May 2026. https://www.ema.europa.eu/en/human-regulatory-overview/research-development/prime-priority-medicines
10. [10]U.S. Food and Drug Administration. Expanded Access Program Report (May 2018); and For Physicians: How to Request Single Patient Expanded Access (Compassionate Use). https://www.fda.gov/media/119971/download
11. [11]U.S. Food and Drug Administration. Expanded Access: Information for Patients. FDA.gov. https://www.fda.gov/news-events/expanded-access/expanded-access-information-patients
12. [12]Tufts Center for the Study of Drug Development (CSDD). Data reported in Drug Developers Actively Improving Efficiency of Clinical Trials. Biospace/Marketwire, April 26, 2011. https://www.biospace.com/drug-developers-actively-improving-efficiency-of-clinical-trials-according-to-tufts-center-for-the-study-of-drug-development
13. [13]U.S. Food and Drug Administration. Conducting Clinical Trials With Decentralized Elements: Guidance for Industry, Investigators, and Other Interested Parties. Final guidance, September 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/conducting-clinical-trials-decentralized-elements
14. [14]Ramamoorthy A, et al. Racial/Ethnic Differences in Drug Disposition and Response: Review of Recently Approved Drugs. Clinical Pharmacology & Therapeutics. 2015;97(3):263-273. https://pmc.ncbi.nlm.nih.gov/articles/PMC10383154/
15. [15]Chaudhary NS, et al. New Strategies for Enhancing Enrollment of Underrepresented Minorities in Lymphoma Clinical Trials. Blood Advances, American Society of Hematology, 2024. https://ashpublications.org/bloodadvances/article/9/4/774/534324
16. [16]Harvey RD, et al. Cancer. 2024;130:1193. Cited in AACR. Disparities in Clinical Research and Cancer Treatment. AACR Cancer Progress Report 2024. https://cancerprogressreport.aacr.org/disparities/cdpr24-contents/cdpr24-disparities-in-clinical-research-and-cancer-treatment/
17. [17]U.S. Food and Drug Administration. Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies. Draft Guidance for Industry, June 2024. (Restored per court order, February 11, 2025.) https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-action-plans-improve-enrollment-participants-underrepresented-populations-clinical-studies
18. [18]ICH / U.S. Food and Drug Administration. E8(R1) General Considerations for Clinical Studies: Guidance for Industry. April 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e8r1-general-considerations-clinical-studies
19. [19]Kehl KL, et al. Identifying Oncology Clinical Trial Candidates Using Artificial Intelligence Predictions of Treatment Change: A Pilot Implementation Study. JCO Precision Oncology. 2024;8:e2300507. https://doi.org/10.1200/PO.23.00507
20. [20]Dolin RH, Arafat W, Heale BSE, Shenvi E, Chamala S, et al. Molecularly-Guided Cancer Clinical Trial Matching using FHIR and HL7 Clinical Quality Language: A Proof of Concept. AMIA Annual Symposium Proceedings. 2024:359-367. https://pmc.ncbi.nlm.nih.gov/articles/PMC12099354/
21. [21]U.S. Food and Drug Administration, CDER. CDER Brings Many Safe and Effective Therapies to Patients and Consumers in 2024. FDA Voices, January 2025. https://www.fda.gov/news-events/fda-voices/cder-brings-many-safe-and-effective-therapies-patients-and-consumers-2024
22. [22]Zanello G, Garrido-Estepa M, Crespo A, O'Connor D, Nabbout R, et al. (IRDiRC Task Force). Targeting Shared Molecular Etiologies to Accelerate Drug Development for Rare Diseases. EMBO Molecular Medicine. 2023;e17159. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331571/
23. [23]European Medicines Agency. ICH Guideline E8(R1) on General Considerations for Clinical Studies. EMA.europa.eu, 2022. https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/ich-guideline-e8-r1-general-considerations-clinical-studies_en.pdf
24. [24]Jin Q, et al. Matching Patients to Clinical Trials with Large Language Models. Nature Communications. 2024;15(1). https://www.nature.com/articles/s41467-024-53081-z
25. [25]Jarow JP, Lemery S, Bugin K, Khozin S, Moscicki R. Impact of Expanded Access on FDA Regulatory Action and Product Labeling. Therapeutic Innovation & Regulatory Science. 2017;51(6):787-789. https://pmc.ncbi.nlm.nih.gov/articles/PMC6075680/
26. [26]U.S. Food and Drug Administration. Right to Try. FDA Patients page. https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try
27. [27]U.S. Food and Drug Administration. The Drug Development Process. FDA Patients page. https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process
28. [28]Kim ES, Bruinooge SS, Roberts S, et al. Broadening Eligibility Criteria to Make Clinical Trials More Representative: ASCO and Friends of Cancer Research Joint Research Statement. Journal of Clinical Oncology. 2017;35(33):3737-3744. https://pubmed.ncbi.nlm.nih.gov/28968170/
29. [29]Getz K, Stergiopoulos S, Short M, et al. New Benchmarks on Protocol Amendment Practices, Trends and Their Impact on Clinical Trial Performance. Therapeutic Innovation & Regulatory Science. 2024;58(2):368-377. https://pubmed.ncbi.nlm.nih.gov/38438658/