Orphanet. The Portal for Rare Diseases and Orphan Drugs 2012. https://www.orpha.net/consor/cgi-bin/Education_AboutRareDiseases.php?lng=EN.

The The Food Drug Administration United, States. Rare diseases at FDA. https://www.fda.gov/patients/rare-diseases-fda. Accessed Dec 2022.

Medicines for rare diseases: orphan drugs. https://eur-lex.europa.eu/EN/legal-content/summary/medicines-for-rare-diseases-orphan-drugs.html. Accessed Dec 2022.

Ferreira CR. The burden of rare diseases. Am J Med Genet A. 2019;179(6):885–92.

Article  PubMed  Google Scholar 

Winter E, Schliebner S. Current advances in clinical trials for rare disease populations: spotlight on the patient. Curr Rev Clin Exp Pharmacol. 2022;17(1):39–45.

Article  PubMed  Google Scholar 

Borysowski J, Górski A. Ethics framework for treatment use of investigational drugs. BMC Med Eth. 2020;21(1):116.

Article  Google Scholar 

Food and Drug Administration. Food and Drug Administration modernization act of 1997. https://www.fda.gov/regulatory-information/selected-amendments-fdc-act/food-and-drug-administrationmodernization-act-fdama-1997. Accessed Feb 2022.

Food and Drug Administration. Expanded access program report. https://www.fda.gov/media/119971/download. Accessed Feb 2022.

European Medicines Agency. Guideline for compassionate use of medicinal products, pursuant to article 83 of regulation (EC) No 726/2004. https://www.ema.europa.eu/en/human-regulatory/research-development/scientific-guidelines. Accessed Feb 2022.

Part 312 - Investigational New Drug Application. https://ecfr.io/cgi-bin/textidx?SID=c7f297d02ba280e799a012f70d549fae&mc=true&node=pt21.5.312&rgn=div5#sp21.5.312.i. Accessed Feb 2022.

Fujiwara Y, Goto Y, Kanda S, Horinouchi H, Yamamoto N, Sakiyama N, Ando Makihara R, Ohe Y. Efficacy and safety of osimertinib in a Japanese compassionate use program. Jpn J Clin Oncol. 2017;47(7):625–9.

Article  PubMed  Google Scholar 

Rambaldi A, Iurlo A, Vannucchi AM, Martino B, Guarini A, Ruggeri M, von Bubnoff N, De Muro M, McMullin MF, Luciani S, et al. Long-term safety and efficacy of givinostat in polycythemia vera: 4-year mean follow up of three phase 1/2 studies and a compassionate use program. Blood Cancer J. 2021;11(3):53.

Article  PubMed  PubMed Central  Google Scholar 

Food and Drug Administration. Expanded Access (Compassionate Use) Submission Data.

Global Diagnostic Information Standard of the 11th Revision of the International Classification of Diseases. https://icd.who.int/browse11/l-m/zh. Accessed Jan 2023.

AIFA's Drug Database. https://farmaci.agenziafarmaco.gov.it/bancadatifarmaci/cerca-farmaco. Accessed Jan 2023.

Agencia Española de Medicamentosy Productos Sanitarios. https://www.aemps.gob.es/. Accessed Jan 2023.

The DailyMed database. https://dailymed.nlm.nih.gov/dailymed/. Accessed Jan 2023.

Health Products Regulatory Authority. https://www.hpra.ie/. Accessed Jan 2023.

Austrian Federal Office for Safety in Health Care. https://www.basg.gv.at/en/. Accessed Jan 2023.

Bundesministerium für Gesundheit. https://www.bundesgesundheitsministerium.de/. Accessed Jan 2023.

Medicines and Healthcare products Regulatory Agency. https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency. Accessed Jan 2023.

Armenia: Drug and Medical Technology Agency. http://www.bmsg.gv.at/bmsg/relaunch/gesundheit/welcome.htm. Accessed Jan 2023.

Therapeutic Goods Administration. https://www.tga.gov.au/. Accessed Jan 2023.

Taiwan Drug Administration. https://www.fda.gov.tw/TC/index.aspx. Accessed Jan 2023.

National medical products adminstration. https://www.nmpa.gov.cn/. Accessed Jan 2023.

L’Agence nationalede sécurité du médicamentet des produits de santé. https://ansm.sante.fr/. Accessed Jan 2023.

The Norwegian Medicines Agency. https://legemiddelverket.no/english.

Medicines Evaluation Board: CBG/MEB. https://english.cbg-meb.nl/. Accessed Jan 2023.

Federal Agency for Medicines and Health Products (FAMHP). https://www.famhp.be/en. Accessed Jan 2023.

Cecinati V, Giordano P, De Leonardis F, Grassi M, Arcamone G, De Mattia D, Santoro N. Hepatic veno-occlusive disease during chemotherapy for nephroblastoma: successful and safe treatment with defibrotide. Rep Clin Case Immunopharmacol Immunotoxicol. 2009;31(4):702–5.

Article  CAS  Google Scholar 

Fernández-Cooke E, Cruz-Rojo J, Gallego C, Romance AI, Mosqueda-Peña R, Almaden Y. Sánchez del Pozo J: tumor-induced rickets in a child with a central giant cell granuloma: a case report. Pediatrics. 2015;135(6):e1518-1523.

Article  PubMed  Google Scholar 

Gavin PJ, Katz BZ. Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children. Pediatrics. 2002;110(1 Pt 1):e9.

Article  PubMed  Google Scholar 

Hall MD, Odia Y, Allen JE, Tarapore R, Khatib Z, Niazi TN, Daghistani D, Schalop L, Chi AS, Oster W, et al. First clinical experience with DRD2/3 antagonist ONC201 in H3 K27M-mutant pediatric diffuse intrinsic pontine glioma: a case report. J Neurosurg Pediatr. 2019;23(6):719–25.

Article  PubMed  Google Scholar 

Zhu X, McDowell MM, Newman WC, Mason GE, Greene S, Tamber MS. Severe cerebral edema following nivolumab treatment for pediatric glioblastoma: case report. J Neurosurg Pediatr. 2017;19(2):249–53.

Article  PubMed  Google Scholar 

Forde K, Resta N, Ranieri C, Rea D, Kubassova O, Hinton M, Andrews KA, Semple R, Irvine AD, Dvorakova V. Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome. Orphanet J Rare Dis. 2021;16(1):109.

Article  PubMed  PubMed Central  Google Scholar 

Takahashi T, Prensner JR, Robson CD, Janeway KA, Weigel BJ. Safety and efficacy of gamma-secretase inhibitor nirogacestat (PF-03084014) in desmoid tumor: report of four pediatric/young adult cases. Pediatr Blood Cancer. 2020;67(10):e28636.

Article  CAS  PubMed  Google Scholar 

Hanzer M, Nebl A, Spendel S, Pilhatsch A, Urban C, Benesch M. Necrosis of a skin autograft after short-term treatment with sunitinib in a 14-year-old girl with metastatic alveolar soft part sarcoma of the thigh. Klin Padiatr. 2010;222(3):184–6.

Article  CAS  PubMed  Google Scholar 

Shee K, Ahn J, Hamouche F, Mena J, Chi T, Stoller ML. Nedosiran dramatically reduces serum oxalate in dialysis-dependent primary hyperoxaluria 1: a compassionate use case report. Urology. 2021;156:e147–9.

Article  PubMed  Google Scholar 

Serban M, Skotnicki AB, Colovic M, Jinca C, Klukowska A, Laguna P, Wolf DM. Clinical efficacy, safety and pharmacokinetic properties of the plasma-derived factor IX concentrate Haemonine in previously treated patients with severe haemophilia B. Haemophilia. 2012;18(2):175–81.

Article  CAS  PubMed  Google Scholar 

Chan D, Kaplan J, Gordon G, Desai J. Activity of the gamma secretase inhibitor AL101 in desmoid tumors: a case report of 2 adult cases. Curr Oncol (Toronto, Ont). 2021;28(5):3659–67.

Article  Google Scholar 

Kerber R, Lorenz E, Duraffour S, Sissoko D, Rudolf M, Jaeger A, Cisse SD, Camara AM, Miranda O, Castro CM, et al. Laboratory findings, compassionate use of favipiravir, and outcome in patients with Ebola virus disease, Guinea, 2015-A retrospective observational study. J Infect Dis. 2019;220(2):195–202.

Article  PubMed  PubMed Central  Google Scholar 

Rumi E, Milosevic JD, Casetti I, Dambruoso I, Pietra D, Boveri E, Boni M, Bernasconi P, Passamonti F, Kralovics R, et al. Efficacy of ruxolitinib in chronic eosinophilic leukemia associated with a PCM1-JAK2 fusion gene. J Clin Oncol: Off J Am Soc Clin Oncol. 2013;31(17):e269-271.

Article  Google Scholar 

Palomo-Arellano A, Cervigón-González I, Torres-Iglesias LM. Effectiveness of bosentan in the treatment of ischemic lesions in a case of thromboangiitis obliterans (Buerger disease): a case report. Dermatol Online J. 2011;17(7):4.

Article  PubMed  Google Scholar 

Wong HH, Bentley H, Bulusu VR, Anyaegbu G, Watkins J, Horan G, Hatcher H. Lorlatinib for the treatment of inflammatory myofibroblastic tumour with TPM4-ALK fusion following failure of entrectinib. Anticancer Drugs. 2020;31(10):1106–10.

Article  CAS  PubMed  Google Scholar 

Richardson PG, Elias AD, Krishnan A, Wheeler C, Nath R, Hoppensteadt D, Kinchla NM, Neuberg D, Waller EK, Antin JH, et al. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population. Blood. 1998;92(3):737–44.

CAS  PubMed  Google Scholar 

Hewison C, Bastard M, Khachatryan N, Kotrikadze T, Hayrapetyan A, Avaliani Z, Kiria N, Yegiazaryan L, Chumburidze N, Kirakosyan O, et al. Is 6 months of bedaquiline enough? Results from the compassionate use of bedaquiline in Armenia and Georgia. Int J Tuberc Lung Dis. 2018;22(7):766–72.

Article  CAS  PubMed  Google Scholar 

Wang ES, Aplenc R, Chirnomas D, Dugan M, Fazal S, Iyer S, Lin TL, Nand S, Pierce KJ, Shami PJ, et al. Safety of gemtuzumab ozogamicin as monotherapy or combination therapy in an expanded-access protocol for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2020;61(8):1965–73.

Article  CAS  PubMed  Google Scholar 

Hughes B, Yip D, Goldstein D, Waring P, Beshay V, Chong G. Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: case report. BMC Cancer. 2004;4:74.

Article  PubMed  PubMed Central  Google Scholar 

Konkle BA, Bauer KA, Weinstein R, Greist A, Holmes HE, Bonfiglio J. Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures. Transfusion. 2003;43(3):390–4.

Article  CAS  PubMed  Google Scholar 

Huang CE, Wu YY, Hsu CC, Chen YJ, Tsou HY, Li CP, Lai YH, Lu CH, Chen PT, Chen CC. Real-world experience with ropeginterferon-alpha 2b (Besremi) in philadelphia-negative myeloproliferative neoplasms. J Formos Med Assoc. 2021;120(2):863–73.

Article  CAS  PubMed  Google Scholar 

Alcaide J, Delgado M, Legeren M, Jurado JM, Blancas I, Pereda T, Lopez J, Garrido M, Sanchez MJ, Garcia JL, et al. Efficacy and safety of aflibercept in metastatic colorectal cancer pretreated with bevacizumab: a report of five cases. Oncol Lett. 2016;12(5):3127–34.

Article  PubMed  PubMed Central  Google Scholar 

Candelaria M, Burgos S, Ponce M, Espinoza R, Duenas-Gonzalez A. Encouraging results with the compassionate use of hydralazine/valproate (TRANSKRIP) as epigenetic treatment for myelodysplastic syndrome (MDS). Ann Hematol. 2017;96(11):1825–32.

Article  CAS  PubMed  Google Scholar 

Zt Y. L H: Compassionate use of polatuzumab vedotin in patients with relapsed/refractory diffuse large B-cell lymphoma: Report of one case and review of literature. Evid Based Med. 2020;20(02):72–5.

Google Scholar 

Robin C, Thiebaut A, Alain S, Sicre de Fontbrune F, Berceanu A, D’Aveni M, Ceballos P, Redjoul R, Nguyen-Quoc S, Benard N, et al. Letermovir for secondary prophylaxis of cytomegalovirus infection and disease after allogeneic hematopoietic cell transplantation: results from the French compassionate program. Biol Blood Marrow Transplant. 2020;26(5):978–84.

Article  CAS  PubMed