scholarly journals Time to inclusion in clinical guidance documents for non-oncological orphan drugs and biologics with expedited FDA designations: a retrospective survival analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e057744
Author(s):  
Ryan Rodriguez ◽  
Rachel Brunner ◽  
Samantha Spencer ◽  
Dima M Qato
Keyword(s):  
Survival Analysis ◽  
Fast Track ◽  
Orphan Drugs ◽  
Priority Review ◽  
Guidance Document ◽  
Entire Cohort ◽  
Fda Approval ◽  
Life Threatening ◽  
Guidance Documents ◽  
Accelerated Approval

ObjectivesDrug and biological products that treat rare, serious or life-threatening conditions can receive US Food and Drug Administration (FDA) orphan designation and expedited programme designations (accelerated approval, breakthrough therapy, fast track or priority review) meant to incentivise development. Timely recommendations from guidance documents may encourage more rapid and appropriate use and access to these medicines for serious conditions. We sought to determine time between FDA approval and inclusion in guidance documents for non-oncological orphan products overall and by number and type of expedited programme designations.Design and settingRetrospective survival analysis of non-oncological orphan products with ≥1 expedited designation approved since 1992. In June 2020, PubMed, Turning Research into Practice and Guideline Central databases were searched to identify guidance documents influencing US practice that included each product.Main outcomes and measuresThe primary outcome was time to guidance inclusion, defined as any recommendation on use provided within the recommendation framework used by the guidance document.ResultsAmong 135 included non-oncological orphan products, 97.0% (n=131) were designated with priority review, 49.6% (n=67) fast track, 16.3% (n=22) breakthrough therapy and 14.1% (n=19) accelerated approval. Sixty per cent of products (n=81) received ≥2 designations. Overall, 74.1% (n=100) were included in a guidance document. The median time to inclusion was 2.87 years (IQR 2.21–4.18) for the entire cohort. In survival analyses, guidance inclusion was more likely to occur earlier for products with ≥2 designations (HR, 1.84; 95% CI 1.21 to 2.79) and for those with fast-track designation compared with priority review (HR 1.40; 95% CI 1.02 to 2.0). Of 35 products not included in a guidance document, 54.3% (n=19) were approved in 2018 or later.ConclusionsAmong non-oncological orphan products with priority designations, nearly 3 years had passed between FDA approval and inclusion in any guidance document. These findings suggest that despite efforts to expedite availability, appropriate access to these treatments may be delayed because of the lack of timely guidance on their use in clinical practice.

Faster approvals?: Trends in the use of FDA’s expedited approval programs for oncology medications.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18270-e18270
Author(s):  
Lisa Ambrosini Vadola ◽  
Monique A Pond ◽  
Ann Winter-Vann ◽  
Robin Whitsell
Keyword(s):  
Health Care Providers ◽  
Fast Track ◽  
Priority Review ◽  
Pharmaceutical Companies ◽  
Care Providers ◽  
Regulatory Pathways ◽  
Oncology Drug ◽  
Accelerated Approval ◽  
Fast Track Designation ◽  
Speed To Market

e18270 Background: With the importance of speed-to-market and addressing unmet needs, pharmaceutical companies have sought accelerated approvals through the Food and Drug Administration (FDA). Introduced with the FDA Safety and Innovation Act (FDASIA) of 2012, Breakthrough Therapy Designation (BTD) has become an important mechanism for approval of serious and life-threatening conditions that do not have adequate therapies. Notably, these pathways have been ill-understood by both pharmaceutical companies and health care providers. This study assessed how BTD and other FDA designations have played a role in the approval of oncology drug marketing applications and evaluated trends in the use of these regulatory pathways. Methods: We analyzed publicly available data on novel oncology drug approvals by the FDA from 2012-2016, including the 4 expedited programs for serious conditions (BTD, Accelerated Approval, Fast Track, and Priority Review). Results: Of the 43 novel oncology drugs approved by the FDA between 2012-2016, 42 used at least 1 of the expedited approval programs, including 65% that used ≥2 programs and 35% that used ≥3 programs. The BTD has been used by 15 of the 43 (35%) approved novel oncology drugs since 2012. The use of the BTD, Accelerated Approval pathway, and Priority Review designation among approved oncology drugs has generally increased each year from 2012-2016, while the use of the Fast Track designation has decreased over the same time period. Conclusions: Companies seeking oncology approvals often use more than one expediting strategy. Alone or in combinations, the BTD, Accelerated Approval, and Priority Review have been shown to play an increasingly important role in oncology drug development. Data collected between 2012-2016 suggest that use of BTD is growing more common, while use of the Fast Track designation has decreased among approved oncology drugs. Additional expedited approval programs have remained steady or increased since the FDA introduced BTD. Based on these observations, we anticipate use of the BTD, Accelerated Approval, and Priority Review designation will grow in future oncology drug applications.

scholarly journals The Potential Benefit of Expedited Development and Approval Programs in Precision Medicine

2021 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Ariel Kantor ◽  
Susanne B. Haga
Keyword(s):  
Precision Medicine ◽  
Fast Track ◽  
Unmet Needs ◽  
Drug Approval ◽  
Priority Review ◽  
The Us ◽  
Causes Of Disease ◽  
Accelerated Approval ◽  
Legislative Changes ◽  
Innovative Drugs

Background: Increased understanding of the molecular causes of disease has begun to fulfill the promise of precision medicine with the development of targeted drugs, particularly for serious diseases with unmet needs. The drug approval regulatory process is a critical component to the continued growth of precision medicine drugs and devices. To facilitate the development and approval process of drugs for serious unmet needs, four expedited approval programs have been developed in the US: priority review, accelerated approval, fast track, and breakthrough therapy programs. Methods: To determine if expedited approval programs are fulfilling the intended goals, we reviewed drug approvals by the US Food and Drug Administration (FDA) between 2011 and 2017 for new molecular entities (NMEs). Results: From 2011 through 2017, the FDA approved 250 NMEs, ranging from 27 approvals in 2013 to 46 in 2017. The NME approvals spanned 22 different disease classes; almost one-third of all NMEs were for oncology treatments. Conclusions: As these pathways are utilized more, additional legislative changes may be needed to re-align incentives to promote continued development of innovative drugs for serious unmet needs in a safe, efficacious, and affordable manner.

scholarly journals 1235. On the Edge of Tomorrow: Expedited Regulatory Pathways for Anti-Infective Therapies

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S637-S637
Author(s):  
Cem Atillasoy ◽  
Panagiotis Gourlias
Keyword(s):  
Infectious Disease ◽  
Infectious Diseases ◽  
Drug Development ◽  
Orphan Drug ◽  
Fast Track ◽  
Orphan Drug Status ◽  
Priority Review ◽  
Drug Status ◽  
Development Programs ◽  
Accelerated Approval

Abstract Background The FDA has developed expedited review programs and pathways to increase drug development for products that have a major clinical benefit. These programs include: Fast Track, Orphan Drug Status, Accelerated Approval, Priority Review, Breakthrough Therapy (BTD) and Qualified Infectious Disease Products (QIPD). Given the heightened awareness of infectious diseases--and emerging global threats, such as resistant bacteria and Ebola—academia and industry have developed and received approval for 88 new infectious disease agents. The objective of this study was to assess the use of expedited review pathways for the 88 anti-infective agents that were approved between 2001-2020. FDA Expedited Drug Development Programs Methods We analyzed the FDA Drug Approval Database entitled, “Compilation of CDER New Molecular Entity (NME) Drug and New Biologic Approvals” for anti-infective therapies that were approved after 2000. Anti-infective therapies were defined as agents that were used to treat or prevent infectious diseases and include antibiotics, antivirals and antifungals. Our analysis focused on a comparison of the percentage of approved anti-infective agents that used each of the aforementioned designations across 2 decades (2001-2010 & 2011-2020). A drug may have one, none, or multiple of these designations. Results There were significant differences in the percentage of anti-infective agents approved with priority review, fast track and accelerated approval in 2001-2010 compared to 2011-2020 (See Results Figure 1) BTD and QIDP did not exist until 2012, thus preventing comparisons between decades. QIDP • Between 2012-2020, 16 anti-infectives have been approved with QIDP. From 2017-2020, 40% (n=10) of approved anti-infectives had QIDP. Orphan Drug Status: • Between 2017-2020, 32% of anti-infectives approved have the orphan drug designation. Comparison of FDA Expedited Drug Development Programs use between 2001-2010 and 2011-2020 Conclusion Our findings indicate Priority Review and Fast Track use has increased since 2010 among anti-infective products. Additionally, our analyses indicate that since 2017 there has been increased use of Orphan Drug Status and QIDP. However, there has been limited use of Breakthrough Therapy and Accelerated Approvals. These two pathways should be increasingly considered by academia, industry and the FDA to further expedite innovative anti-infective development. Disclosures All Authors: No reported disclosures

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies

2019 ◽  
Vol 143 (1) ◽  
pp. 73-77
Author(s):  
Anat Gafter-Gvili ◽  
Ariadna Tibau ◽  
Pia Raanani ◽  
Daniel Shepshelovich
Keyword(s):  
Hematological Malignancies ◽  
New Drugs ◽  
Priority Review ◽  
Regulatory Review ◽  
Regulatory Pathways ◽  
The Us ◽  
Black Box Warnings ◽  
Accelerated Approval ◽  
Drug Approvals ◽  
Approved Drugs

The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115–316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.

Evaluation of Orphan Products by the U.S. Food and Drug Administration

1992 ◽  
Vol 8 (4) ◽  
pp. 647-657 ◽  
Author(s):  
Marlene E. Haffner ◽  
John V. Kelsey
Keyword(s):  
Drug Administration ◽  
Rare Diseases ◽  
Food And Drug Administration ◽  
Orphan Drugs ◽  
Marketing Approval ◽  
Drug Products ◽  
Governmental Agencies ◽  
Number Of Patients ◽  
Life Threatening ◽  
The U.S

AbstractOrphan drug products generally are used in treating or preventing rare diseases. The small number of patients available for study may create special problems in the evaluation of these products. This paper examines some of the special problems that are associated with the design and implementation of studies to evaluate the safety and efficacy of orphan drugs. The U.S. Food and Drug Administration (FDA) has not established special criteria for evaluating orphan drugs per se, but the FDA has been flexible in evaluating drug products that present special problems, especially when these products are for treatment of serious of life-threatening illnesses. The FDA and other U.S. governmental agencies also have taken steps to promote the development and availability of drugs for rare diseases, including making these products available to patients who are in need, even before the drugs have full FDA marketing approval.

Contemporary outcomes for adults with AML requiring ICU admission.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7025-7025
Author(s):  
Danielle Hammond ◽  
Koji Sasaki ◽  
Alexis Geppner ◽  
Fadi Haddad ◽  
Shehab Mohamed ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Cancer Center ◽  
Hospital Death ◽  
Entire Cohort ◽  
Morbidity Burden ◽  
Icu Admission ◽  
Poor Risk ◽  
Line Therapy ◽  
Co Morbidity ◽  
Life Threatening

7025 Background: Patients (pts) with AML frequently encounter life-threatening complications requiring transfer to an intensive care unit (ICU). Methods: Retrospective analysis of 145 adults with AML requiring ICU admission at our tertiary cancer center 2018-19. Use of life-sustaining therapies (LSTs) and overall survival (OS) were reported using descriptive statistics. Logistic regression was used to identify risk factors for in-hospital death. Results: Median age was 64 yrs (range 18-86). 47% of pts had an ECOG status of ≥ 2 with a median of at least 1 comorbidity (Table). 117 pts (81%) had active leukemia at admission. 68 pts (47%) had poor-risk cytogenetics (CG) and 32 (22%) had TP53-mutated disease. 61 (42%), 27 (19%) and 57 pts (39%) were receiving 1st, 2nd and ≥ 3rd line therapy. 33 (23%) and 70 pts (48%) were receiving intensive and lower-intensity chemotherapy, respectively, and 77 pts (53%) were concurrently on venetoclax. Most common indications for admission were sepsis (32%), respiratory failure (24%) and leukocytosis (12%); Table outlines additional ICU admission details. Median OS from the date of ICU admission was 2.0 months (mo) for the entire cohort and 6.9, 1.6 and 1.2 mo in pts with favorable-, intermediate- and poor-risk CG. Median OS of pts receiving frontline vs. ≥ 2nd line therapy was 4.2 vs. 1.4 mo (P<0.001). Median OS in pts requiring 0-1 vs. 2-3 LSTs was 4.1 vs. 0.4 mo (P<0.001). OS was not different by age, co-morbidity burden nor therapy intensity. In a multivariate analysis that included SOFA scores, only adverse CG (OR 0.35, P = 0.028), and need for intubation with mechanical ventilation (IMV; OR 0.19, P = 0.009) were associated with increased odds of in-hospital mortality. Conclusions: A substantial portion of pts with AML survive their ICU admission with sufficient functionality to return home and receive subsequent therapy. In contrast to general medical populations, age, co-morbidities, and SOFA scores were not independently predictive of in-hospital mortality. Disease CG risk and the need for IMV were the strongest predictors of ICU survival. This suggests that many pts with AML can benefit from ICU care.[Table: see text]

Diverting Loop Ileostomy for Clostridium Difficile Colitis: A Systematic Review and Meta-analysis

2020 ◽  
Vol 86 (10) ◽  
pp. 1269-1276
Author(s):  
Adam D. Shellito ◽  
Marcia M. Russell
Keyword(s):  
Clostridium Difficile ◽  
Meta Analysis ◽  
Loop Ileostomy ◽  
Patient Characteristics ◽  
Specific Patient ◽  
Entire Cohort ◽  
Significant Difference ◽  
Threatening Condition ◽  
Life Threatening ◽  
Diverting Loop Ileostomy

Diverting loop ileostomy (DLI) with colonic lavage has been proposed as an alternative to total abdominal colectomy (TAC) for fulminant Clostridium difficile infection (CDI). Controversy exists regarding the mortality benefit and outcomes of this surgical approach. We conducted a MEDLINE database search for articles between 1999 and 2019 pertaining to DLI for the surgical treatment of CDI. Five articles met the inclusion criteria. Four studies were retrospective and one was a prospective matched cohort study. 3683 patients were included in the 5 studies; 733 patients (20%) underwent DLI, while 2950 patients (80%) underwent TAC. The only shared outcome measure across all 5 studies was mortality. The overall mortality rate for the entire cohort undergoing both procedures was 30.3%. There was no statistically significant difference in pooled mortality between DLI and TAC (OR: .73; 95% CI, .45-1.2; P = .22). Reporting of other postoperative outcomes was variable. Fulminant CDI remains a life-threatening condition with high mortality. Loop ileostomy may be a viable surgical alternative to total colectomy with similar mortality; however, further work is needed to determine specific patient characteristics that warrant routine use of DLI.

scholarly journals Diversity for diversity: A “fast track” nursing service model to complement conventional emergency medicine service in a busy urban area emergency department

2020 ◽  
pp. 102490792093170
Author(s):  
Ng Hing Yin ◽  
Fan Kin Ping ◽  
Lo Chor Man
Keyword(s):  
Emergency Department ◽  
Patient Satisfaction ◽  
Fast Track ◽  
Waiting Times ◽  
Clinical Protocols ◽  
Service Model ◽  
Nursing Service ◽  
Life Threatening ◽  
Emergency Department Patients ◽  
High Level

Background: In a busy local emergency department, patients with certain non-life-threatening conditions which only require relatively quick and straightforward management may encounter long waiting times. A new service model called the “Fast Track” Nursing Service attempts to lessen the service load of the regular service queues and to improve patient outcomes. Objectives: This article reports the service outcomes of the Fast Track Nursing Service. Methods: Nurses at our department are selected and trained under clinical protocols specially developed for this service. Assessments and quality assurance audits ensure the quality of service. Results: This service resulted in comparatively shorter waiting times for patients included in predetermined clinical protocols. There was also a high level of patient satisfaction with this service. Conclusion: Our Fast Track Enhanced Nursing service is a model of tailored service diversification to shorten waiting times, thus improving patient satisfaction and outcome.

Hidden Politics? Assessing Lobbying Success During US Agency Guidance Development

2020 ◽  
Vol 30 (4) ◽  
pp. 548-562 ◽  
Author(s):  
Susan Webb Yackee
Keyword(s):  
Interest Groups ◽  
Development Process ◽  
Guidance Document ◽  
Public Attention ◽  
Policy Success ◽  
Government Documents ◽  
Us Government ◽  
Guidance Documents ◽  
The Relationship ◽  
Guidance Development

Abstract I test the proposition that interest groups achieve greater policy success when they lobby during the agency guidance document development process as opposed to the notice and comment process. Policymaking via guidance documents often receives lower levels of public attention, which provides greater flexibility to accommodate lobbying requests. I analyze the hypothesis during the creation of 41 rules by one US government agency—20 of which were promulgated using the notice and comment process and 21 via the guidance document process. I measure regulatory policy change using a content analysis of government documents and lobbying texts, and I also incorporate a telephone survey of interest groups who lobbied on these same rules. I find that interest groups perceive—and achieve—greater policy success when lobbying during the agency guidance process. The results yield new insights into the relationship between lobbying and regulatory policymaking.

scholarly journals International Council for Standardization in Haematology Recommendations for Hemostasis Critical Values, Tests, and Reporting

2019 ◽  
Vol 46 (04) ◽  
pp. 398-409 ◽  
Author(s):  
Robert C. Gosselin ◽  
Dorothy Adcock ◽  
Akbar Dorgalaleh ◽  
Emmanuel J. Favaloro ◽  
Giuseppe Lippi ◽  
...  
Keyword(s):  
Ad Hoc ◽  
Test List ◽  
Published Data ◽  
Guidance Document ◽  
International Council ◽  
Hospital Managers ◽  
Coagulation Tests ◽  
Good Laboratory ◽  
Guidance Documents ◽  
Institutional Stakeholders

AbstractThis guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH), the aim of which is to provide hemostasis-related guidance documents for clinical laboratories. The current ICSH document was developed by an ad hoc committee, comprising an international collection of both clinical and laboratory experts. The purpose of this ICSH document is to provide laboratory guidance for (1) identifying hemostasis (coagulation) tests that have potential patient risk based on analysis, test result, and patient presentations, (2) critical result thresholds, (3) acceptable reporting and documenting mechanisms, and (4) developing laboratory policies. The basis for these recommendations was derived from published data, expert opinion, and good laboratory practice. The committee realizes that regional and local regulations, institutional stakeholders (e.g., physicians, laboratory personnel, hospital managers), and patient types (e.g., adults, pediatric, surgical) will be additional confounders for a given laboratory in generating a critical test list, critical value thresholds, and policy. Nevertheless, we expect this guidance document will be helpful as a framework for local practice.

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