Clinical Trial 
Considerations to 
Support Accelerated 
Approval of Oncology 
Therapeutics 
Guidance for Industry 
 
DRAFT GUIDANCE
 
 
  This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit 
electronic comments to https://www.regulations.gov. Submit written comments to the Dockets 
Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, 
MD 20852. All comments should be identified with the docket number listed in the notice of availability 
that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (OCE/CDER) Lola Fashoyin-Aje at 240-402-0205 or 
(CBER) Office of Communication, Outreach and Development at 800-835-4709 or 240-402-8010.  
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Oncology Center of Excellence (OCE) 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
March 2023 
Clinical/Medical 
   
Clinical Trial 
Considerations to 
Support Accelerated 
Approval of Oncology 
Therapeutics 
Guidance for Industry 
 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information  Office of Communication, Outreach and Development 
Center for Drug Evaluation and Research  Center for Biologics Evaluation and Research 
Food and Drug Administration  Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002  Silver Spring, MD 20993-0002 
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353  Phone: 800-835-4709 or 240-402-8010 
Email: druginfo@fda.hhs.gov  Email: ocod@fda.hhs.gov 
https://www.fda.gov/drugs/guidance-compliance-regulatory- https://www.fda.gov/vaccines-blood-biologics/guidance-
information/guidances-drugs  compliance-regulatory-information-biologics/biologics-
  guidances 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Oncology Center of Excellence (OCE) 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
March 2023 
Clinical/Medical  
   
TABLE OF CONTENTS 
 
 
I.  INTRODUCTION..................................................................................................1 
II.  BACKGROUND ....................................................................................................1 
III.  RECOMMENDATIONS .......................................................................................3 
A.  Randomized Controlled Clinical Trials to Support Accelerated Approval .....4 
B.  Single-Arm Trials to Support Accelerated Approval .........................................7 
C.  Confirmatory Trial Following Accelerated Approval ........................................9 
 
 
 
 
 
 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
Clinical Trial Considerations to Support Accelerated Approval of 
1 
Oncology Therapeutics  
2 
Guidance for Industry1 
3 
4   
5   
6   
7  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
8  Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not 
9  binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the 
10  applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible 
11  for this guidance as listed on the title page. 
12   
13   
14   
15   
16  I.  INTRODUCTION  
17   
18  The purpose of this guidance is to provide recommendations to sponsors of anti-cancer drugs or 
19  biological products2 on considerations for designing trials intended to support accelerated 
20  approval.  
21   
22  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
23  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
24  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
25  the word should in Agency guidances means that something is suggested or recommended, but 
26  not required. 
27   
28   
29  II.  BACKGROUND 
30   
31  The accelerated approval pathway3 is commonly used for approval of oncology drugs in part due 
32  to the serious and life-threatening nature of cancer and because of available surrogate or 
33  intermediate clinical endpoints considered reasonably likely to predict clinical benefit. While a 
34  variety of trial designs and endpoints have historically been used to support accelerated approval, 
35  single-arm trial designs and response endpoints (with duration of response as supportive) have 
 
1 This guidance has been prepared by the Oncology Center of Excellence (OCE) in collaboration with the Center for 
Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) at the Food 
and Drug Administration.  
 
2 For the purposes of this guidance, references to drugs include drugs approved under section 505 of the Federal 
Food, Drug, and Cosmetic Act (21 U.S.C. 355) and biological products licensed under section 351 of the Public 
Health Service Act (42 U.S.C. 262). 
 
3 See section 506(c) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356(c)); 21 CFR part 314, subpart H; 
21 CFR part 601, subpart E. 
 
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36  most commonly been used in oncology. Response rate is a marker of drug activity because 
37  malignant tumors do not typically regress on their own, and because this endpoint can be 
38  interpreted in single-arm trials for monotherapy oncology drug regimens. However, there are 
39  limitations to the use of single-arm trials in support of accelerated approval, including but not 
40  limited to the following:  
41   
42    Safety databases are typically small and may not allow for the identification of rare, 
43  potentially serious adverse events. For identified serious adverse events, attribution of 
44  adverse events to the drug under study can be limited in the absence of a comparator arm.  
45   
46    Common time-to-event efficacy endpoints in oncology (e.g., tumor progression, survival) 
47  are generally uninterpretable due to failure to account for known and unknown 
48  confounding factors when comparing the results to an external control. FDA considers 
49  such endpoints exploratory and not adequate to be used as measures of efficacy in single-
50  arm trials intended to support approval.4  
51   
52    Low magnitude response rates generally may not be reasonably likely to predict clinical 
53  benefit (e.g., immunotherapy).5  
54   
55    For combination regimens, the contribution of the individual components to the claimed 
56  effect(s) generally may be challenging to establish.6  
57   
58    Reliance on cross-trial comparisons to historical trials to assess whether the observed 
59  treatment effect represents an improvement over available therapy is challenging.7 There 
60  can be differences across trials (e.g., in design, conduct, response assessment intervals, 
61  study population, etc.) which may or may not be easily discernible and which could lead 
62  to erroneous conclusions regarding observed differences in the response estimate between 
63  the investigational arm and a historical control (e.g., erroneously attributing differences in 
64  response rate to the investigational drug).  
65   
66  These and other limitations of single-arm trials can add uncertainty to the assessment of the 
67  safety and/or effectiveness of a drug such that accelerated approval based on a single-arm trial 
68  may not be justified in a given clinical setting.  
69   
70  When properly designed and executed, a randomized controlled trial can address the limitations 
71  of single-arm trials, including but not limited to, the following ways: 
72    
 
4 See the guidance for industry Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics (December 
2018). We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web 
page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
5 Beaver J, Pazdur R, 2021, Dangling Accelerated Approvals in Oncology, N Engl J Med, 384(18):e68.  
 
6 See 21 CFR 300.50. 
 
7 See 21 CFR 314.126(b)(2)(v).  
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73    A randomized controlled trial provides a more robust efficacy and safety assessment and 
74  allows for direct comparison to a concurrent control arm.  
75   
76    In cases wherein historical trials did not specifically evaluate the response rate for the 
77  standard of care treatment in a biomarker-selected population of interest (i.e., available 
78  therapy is approved for an all-comer population), assessing the new drug compared to the 
79  available therapy in the same trial provides a more accurate representation of the efficacy 
80  and safety of standard of care in the biomarker-defined cohort of patients.  
81   
82    In settings wherein the treatment landscape may have changed since completion of the 
83  trial(s) for available therapy, a randomized controlled trial enables comparable study 
84  populations to be studied.  
85   
86    While trials that support accelerated approval have typically been conducted in patients 
87  with refractory disease, a randomized controlled trial may allow for the evaluation of a 
88  new drug in an earlier treatment setting, thereby enabling access to a new drug earlier in 
89  the course of the disease when more patients are likely to benefit. 
90   
91    When clinical trial sites span several geographic regions as would be the case for trials 
92  that enroll participants internationally, a randomized controlled trial allows for an 
93  assessment of potential regional differences that may stem from multiple factors.  
94   
95  Another potential advantage to conducting a randomized controlled trial to support accelerated 
96  approval is that, in appropriate cases, longer term follow-up in the same trial could fulfill a 
97  postmarketing requirement to verify clinical benefit. This one-trial approach maintains 
98  efficiency in drug development and can provide early access to a drug using the accelerated 
99  approval pathway, while ensuring that a postmarketing trial is fully accrued and well underway 
100  to verify longer term benefit in a timely fashion.  
101   
102   
103  III.  RECOMMENDATIONS 
104   
105  Given the limitations of single-arm trials, a randomized controlled trial is the preferred approach 
106  to support an application for accelerated approval. Sponsors can, as appropriate, elect to conduct 
107  a single randomized controlled trial to support an accelerated approval and to verify clinical 
108  benefit (i.e., follow a one-trial approach) or, they can conduct separate trials  one to support 
109  the accelerated approval and another, a confirmatory trial, to verify clinical benefit.  
110   
111  Although a randomized controlled trial is the preferred approach, there can be circumstances 
112  wherein a single-arm trial is appropriate in the development of a drug for accelerated approval, 
113  for example when there are significant concerns about the feasibility of a randomized controlled 
114  trial. Careful consideration should be taken in determining whether a single-arm trial is 
115  appropriate in a particular clinical and regulatory context. Regardless of the approach under 
116  consideration, FDA recommends early discussion with the Agency before initiating and, as 
117  appropriate, during the conduct of, a trial(s).  
118   
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119  A.  Randomized Controlled Clinical Trials to Support Accelerated Approval 
120   
121  Sponsors can conduct separate randomized controlled trials  one trial with an early endpoint 
122  (e.g., response rate) to support the accelerated approval of the drug and a second trial powered 
123  for a longer-term clinical endpoint (e.g., progression-free survival (PFS) or overall survival 
124  (OS)) to verify clinical benefit. Alternatively, sponsors could design a single randomized 
125  controlled trial to support accelerated approval, that is also powered for the longer-term clinical 
126  endpoint with follow-up in the same trial to verify clinical benefit (i.e., one-trial approach).8 
127  Below are recommendations for addressing the design, conduct, and analyses of data for either 
128  two separate randomized controlled clinical trials or for using the one-trial approach for 
129  accelerated approval and to verify clinical benefit.  
130   
131  1.  Considerations for Two Randomized Controlled Clinical Trials  
132   
133    Waiting to initiate a randomized controlled confirmatory trial until after an accelerated 
134  approval has been granted can create challenges in enrolling participants due to the 
135  availability of the drug in clinical practice. Therefore, to help ensure the feasibility and 
136  timely completion of the trial intended to verify clinical benefit, FDA strongly 
137  recommends that this trial be well underway, if not fully enrolled, by the time of the 
138  accelerated approval action.9,10 
139   
140    To facilitate completion of the confirmatory trial, it may be acceptable to evaluate the 
141  drug in the same cancer type but in another line of therapy. For instance, for an 
142  accelerated approval granted for an indication in a refractory cancer setting, the 
143  confirmatory trial could be conducted in an earlier disease setting. This approach has the 
144  potential to provide access to effective drugs to patients with earlier-stage disease in 
145  which benefit may be greater, and it facilitates patient accrual when a drug has already 
146  received accelerated approval for a later-stage indication.11  
147   
148    Given the inherent and residual uncertainties regarding the clinical benefit of the drug at 
149  the time of accelerated approval, timely completion of the trial(s) intended to verify 
150  clinical benefit is critical. Confirmatory trials should be underway when the marketing 
151  application is submitted.12  
 
8 This one-trial approach may be an efficient way to verify clinical benefit for a drug after accelerated approval. 
Whether a single trial satisfies the substantial evidence requirement in section 505(d) of the Federal Food, Drug, and 
Cosmetic Act, should be discussed with FDA early in clinical development, no later than prior to initiating such a 
trial. 
 
9 See section 506(c) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356(c)). We note that section 506(c) of 
the Federal Food, Drug, and Cosmetic Act was recently amended to provide that FDA may require, as appropriate, 
a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of 
the applicable product.   
 
10 See the guidance for industry Expedited Programs for Serious Conditions  Drugs and Biologics (May 2014).  
 
11 Ibid, p.23.  
 
12 Ibid, p.22. 
4  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
152   
153  1.  Considerations for a Single Randomized Controlled Trial to Support Accelerated 
154  Approval and to Verify Clinical Benefit 
155   
156    If planning a one-trial approach that uses the same trial to potentially support 
157  accelerated approval with longer term follow-up to verify clinical benefit, sponsors 
158  should carefully assess the available preliminary clinical data prior to initiating the trial. 
159  FDA recommends selection of an endpoint for accelerated approval that is appropriate 
160  and feasible to evaluate earlier in the disease and earlier during the conduct of the trial.13 
161  Sponsors should also consider the natural history of the disease (e.g., indolent cancers), 
162  the mechanism of action of the investigational drug, the ability to reliably characterize 
163  measurable disease to assess response, and other context-specific factors in selecting the 
164  accelerated approval endpoint.  
165   
166    Preserving the integrity of the trial is critical in assessing the feasibility and 
167  appropriateness of the one-trial approach because the evaluation of the data and 
168  subsequent regulatory action on an accelerated approval application may inadvertently 
169  introduce bias. In assessing the potential for bias, sponsors should consider factors such 
170  as the anticipated impact of crossover (if permitted); the preliminary data on the drugs 
171  effects, including the toxicity profile, the treatment landscape, and the treatment used in 
172  the control arm, among other factors.   
173   
174    Before initiating the trial, sponsors should consider and discuss with FDA whether based 
175  on the available preliminary clinical data, the expected effect on response rate or other 
176  early endpoint is of a sufficient magnitude to be reasonably likely to predict clinical 
177  benefit. Depending on the disease course, the intended population, and guidance from 
178  FDA, use of endpoints other than response rate could also be evaluated in a one-trial 
179  approach together with subsequent evaluation of clinical benefit endpoints.  
180   
181    If the drug development program is intended to evaluate a combination regimen, sponsors 
182  should specify the approach for demonstrating the contribution of each component. 
183  Evidence should be provided to support the individual contribution of components to the 
184  claimed effect(s), which would generally come from multi-arm trials with interim 
185  analyses for futility or from the use of other adaptive trial design elements.14  
186   
187    Sponsors should carefully consider whether the results of the trial are adequate to support 
188  submission of an application. A requirement of accelerated approval is that the drug must 
189  demonstrate an effect on a surrogate endpoint or intermediate clinical endpoint that is 
190  reasonably likely to predict clinical benefit, and provide meaningful advantage over 
191  available therapy.15 Among the factors FDA considers in evaluating whether these 
 
13 See footnote 4.  
 
14 See the guidance for industry Adaptive Designs for Clinical Trials of Drugs and Biologics (December 2019).  
 
15 See footnote 10.  
 
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192  requirements have been met are the statistical significance and clinical meaningfulness of 
193  the treatment effect demonstrated on the endpoint, other context-specific evidence 
194  supporting why the observed effect is likely to predict clinical benefit, and whether the 
195  control arm represents the appropriate available therapy. 
196   
197    If the treatment landscape has evolved since initiation of the trial (e.g., the treatment on 
198  the control arm no longer reflects best available therapy), the decision regarding 
199  submission of an application for accelerated approval versus deferring submission of an 
200  application until the results to support traditional approval are available should be 
201  discussed with FDA. Ultimately, the determination of what constitutes available therapy 
202  is made at the time the regulatory decision is made rather than at the time the trial was 
203  initiated.16  
204   
205    The trial should be designed, executed, and analyzed in such a way as to ensure a robust 
206  assessment of the efficacy endpoints. The protocol should specify a plan to strongly 
207  control the overall false positive rate (type-I error) for the endpoint supporting 
208  accelerated approval and the endpoint supporting verification of clinical benefit. 
209   
210    The trial sample size should be chosen so that it has adequate power to detect a clinically 
211  meaningful and statistically significant improvement in both the endpoints for accelerated 
212  approval (e.g., response rate) and verification of clinical benefit (e.g., PFS or OS). The 
213  trial design can incorporate adaptive design elements (e.g., sample size re-estimation). 
214  With an adaptive design, sponsors should consider the type I error control based on the 
215  context of the between-arm comparisons, address the operational issues that this approach 
216  may raise, and design the trial with timely completion of the trial as a paramount 
217  consideration. For additional information, refer to the guidance for industry Adaptive 
218  Designs for Clinical Trials of Drugs and Biologics (December 2019). 
219   
220    For a response-based endpoint, the analysis to support accelerated approval could be 
221  based on a pre-specified number of initially randomized patients, while for a time-to-
222  event endpoint, pre-specifying the number of events is appropriate; in each case, the 
223  sponsor should ensure a robust assessment and reliable estimation at the earlier analysis 
224  time point. Analyses of efficacy to support accelerated approval should be avoided until 
225  the trial is close to or fully enrolled to mitigate potential challenges in accrual if an 
226  accelerated approval is granted. General considerations for determining the adequacy of 
227  the overall response rate (ORR) data to support accelerated approval are described in 
228  Section B below.  
229   
 
16 See footnote 10, p.4. 
  
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230    Measures should be in place to prevent circumstances that may jeopardize the trial results 
231  or trial integrity.17,18 For example, blinding of data for the endpoint supporting 
232  verification of clinical benefit should be maintained until the endpoints protocol-
233  specified analysis time point is reached to ensure a robust assessment of this endpoint.  
234   
235    In reviewing an application for accelerated approval, FDAs safety assessment may 
236  include evaluating whether the available data suggest a potential for harm from treatment 
237  on the investigational arm (e.g., detrimental effects on clinical endpoints such as OS). 
238  FDA may request summary results of the analysis on survival data to support such an 
239  assessment as part of an application submission and may request updated survival results 
240  during the course of the review of the application. Sponsors should specify a plan that 
241  describes measures to maintain study blind for such an analysis. 
242   
243  B.  Single-Arm Trials to Support Accelerated Approval 
244   
245  As described above, whether a single-arm trial is appropriate to support accelerated approval in a 
246  particular clinical and regulatory context should be discussed with FDA. This section outlines 
247  considerations for designing, conducting, and analyzing data from a single-arm trial intended to 
248  support accelerated approval when appropriate, and considerations for determining whether the 
249  data may be adequate for this purpose.  
250    
251  1.  Study Efficacy Considerations  
252   
253    Endpoints: In oncology, response rate is the most frequently used endpoint to support 
254  accelerated approval when the approval is based on data from single-arm trials. 
255  Appropriate criteria for assessing the response rate (e.g., ORR based on Response 
256  Evaluation Criteria in Solid Tumors [RECIST]19) should be used. In certain disease 
257  settings, measures of response other than ORR may be more appropriate to characterize 
258  efficacy (e.g., complete remission rate, major molecular response, etc.). Use of new 
259  response assessment criteria or modifications of established criteria should be supported 
260  by a strong underlying rationale and should be discussed with FDA at the trial design 
261  stage. Whenever possible, the method of assessing response used in the trial should be the 
262  same one used for product labeling.  
263   
264    Available therapy: Accelerated approval is reserved for drugs that are expected to 
265  provide a meaningful advantage (including an efficacy advantage) over available 
 
17 See the guidance for industry Establishment and Operation of Clinical Trial Data Monitoring Committees (March 
2006).  
 
18 See the guidance for industry Placebos and Blinding in Randomized Controlled Cancer Clinical Trials for Drug 
and Biological Products (August 2019).  
 
19 Eisenhauer EA, P Therasse, J Bogaerts, et al., 2009, New Response Evaluation Criteria in Solid Tumours: Revised 
RECIST guideline (version 1.1), Eur J Cancer, 45(2):228-247.  
 
7  Contains Nonbinding Recommendations 
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266  treatment.20,21 To facilitate the demonstration of advantage over available therapies, 
267  sponsors should pre-specify the historical trial(s) that will serve as the basis for the 
268  comparison, and the rationale for the selected trial(s). The time frame for the trial(s), trial 
269  size, clinical and demographic characteristics of the trial population, and any potential 
270  bias in the assessment of response, are some of the factors to consider in evaluating the 
271  applicability of a historical trial. FDA recognizes that it may be challenging, particularly 
272  for drugs being developed in molecularly defined patient populations, to identify a 
273  historical trial; in such cases, it may be appropriate to provide data to demonstrate that the 
274  magnitude of the treatment effect in the molecularly defined subgroup is better than in the 
275  historical trial.  
276   
277    Sample Size: A single-arm trial should be sized to permit adequate precision around the 
278  point estimate, provide robust estimation of the duration of response, and sufficiently 
279  describe the adverse event profile of the drug. 
280   
281  2.  Trial Analysis Considerations 
282   
283    When the efficacy endpoint is response rate, the adequacy of the result to support 
284  accelerated approval should be based on the magnitude and duration of response. 
285  Sponsors should consider the follow-up time necessary to adequately characterize the 
286  response rate and the durability of response in a particular disease setting (e.g., a rapidly 
287  progressing disease vs. an indolent disease). Statistical inferential procedures are not 
288  necessary to evaluate these endpoints in single-arm trials. In most cases, a minimum 
289  follow-up of six months after the response is needed for most of the responders to 
290  characterize durability of response. However, there may be instances where a longer 
291  minimum follow-up after response is necessary to adequately characterize clinical 
292  benefit. In some cases, FDA may request additional data on the durability of response 
293  during the review of an application. 
294   
295    The trial sample size and analysis population for response should be pre-specified. Given 
296  the small size of most single-arm trials, the analysis population is generally expected to 
297  be the entire trial population. Patients who have received at least one dose of the study 
298  drug would then be included in the analysis population regardless of whether they have 
299  had the opportunity to respond due to short follow-up time. Multiple increases to the 
300  study sample size with repeated looks at the data in the absence of a pre-specified plan 
301  may introduce bias in the assessment of efficacy and should be avoided.  
302   
303    To reduce the potential to introduce bias and to mitigate variance in the assessment of 
304  response, blinded independent central review (BICR) of the response assessment should 
 
20 See 21 CFR 314.500; see also section 506(c)(1)(A) (directing FDA to take into account the availability or lack of 
alternative treatments).   
 
21 See footnote 10.  
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305  be performed.22 A BICR charter that includes procedures for adjudication should be 
306  made available to FDA as part of a marketing application.  
307   
308    Generally, and in the appropriate clinical context, FDA has defined response rate as the 
309  sum of partial responses plus complete responses.23 When defined in this manner, 
310  response is a direct measure of a drugs antitumor activity which can be evaluated in a 
311  single-arm study. Stable disease should not be a component of response rate. Likewise, 
312  measures such as clinical benefit rate (e.g., response rate + stable disease > 6 months) 
313  should not be used. Such measures can largely reflect the natural history of disease, 
314  whereas reduction in tumor size represents a direct therapeutic effect. 
315   
316  C.  Confirmatory Trial Following Accelerated Approval 
317   
318  For drugs granted accelerated approval in oncology, postmarketing confirmatory trials have been 
319  required to verify and describe the anticipated clinical benefit.24 Such trials help address residual 
320  uncertainties regarding the relationship between the surrogate or intermediate endpoint to the 
321  ultimate clinical benefit.25 In order to minimize the duration of this uncertainty, FDA may 
322  require, as appropriate, that studies intended to verify clinical benefit be underway prior to 
323  approval, or within a specified time period after the date of approval, of the applicable product.26 
324  Postmarketing trials must be carried out with due diligence,27 and in accordance with the 
325  postmarketing trial conditions specified by FDA, which may include enrollment targets, the 
326  study protocol, and milestones, including the target date of study completion.28 An advantage of 
327  the one-trial approach is that a separate confirmatory trial may not be necessary. However, 
328  when a single-arm trial supports the accelerated approval, and FDA requires a postmarketing 
329  trial to evaluate PFS or OS, a separate randomized controlled trial may be needed. Early 
330  discussions with FDA regarding the design and initiation of both the trial intended to support 
331  accelerated approval and the postmarketing trial are recommended to provide evidence of 
332  clinical benefit in an expeditious manner. 
 
22 Ford R, Schwartz L, Dancey J, et al., 2009, Lessons learned from independent central review, Eur J Cancer, 
45:268-274.  
 
23 See footnote 4, p.9. 
  
24 21 CFR 314.510. 
 
25 Fashoyin-Aje LA, Mehta GU, Beaver JA, and Pazdur R, 2022, The On- and Off-Ramps of Oncology Accelerated 
Approval. N Engl J Med, 387(16): 1439-1442. 
 
26 See footnote 9. 
 
27 21 CFR 314.510.  
 
28 See Section 506(c)(2)(C) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356(c)(2)(C)). 
9