1e7ed2bc5b0df1b36cfb396dd13e2022 pmc_33668473.pdf a9bfcda31a6277f4695372b47d4a90ceef2f38bb pmc_33668473.pdf 283668dd925433cc8b6a6320232a5a43f1e9a18ee8d86becd7a8aa0312464ed8 pmc_33668473.pdf Title: Are Quality of Randomized Clinical Trials and ESMO-Magnitude of Clinical Benefit Scale Two Sides of the Same Coin, to Grade Recommendations for Drug Approval? Subject: The approval of a new drug for cancer treatment by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) is based on positive, well-designed randomized phase III clinical trials (RCTs). However, not all of them are analyzed to support the recommendations. For this reason, there are different scales to quantify and evaluate the quality of RCTs and the magnitude of the clinical benefits of new drugs for treating solid tumors. In this review, we discuss the value of the progression-free survival (PFS) as an endpoint in RCTs and the concordance between it and the overall survival (OS) as a measure of the quality of clinical trial designs. We summarize and analyze the different scales to evaluate the clinical benefits of new drugs such as the The American Society of Clinical Oncology value framework (ASCO-VF-NHB16) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the concordance between them, focusing on metastatic colorectal cancer (mCRC). We propose several definitions that would help to evaluate the quality of RCT, the magnitude of clinical benefit and the appropriate approval of new drugs in oncology. Keywords: quality randomized studies; ESMO-MCBS; drug approval Author: Adela Rodriguez, Francis Esposito, Helena Oliveres, Ferran Torres and Joan Maurel Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Feb 23 13:01:57 2021 CET ModDate: Tue Feb 23 13:05:10 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 712989 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- DUFXDP+VnURWPalladioL Type 1 Custom yes yes no 10 0 FLNPWT+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 AEOPJR+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 SDALTV+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 32 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 35 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 57 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 61 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 65 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes no 83 0 ICRTVP+CMSY10 Type 1 Builtin yes yes no 87 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 114 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 118 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 122 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 126 0 Arial TrueType WinAnsi no no no 133 0 ABCDEE+Palatino Linotype,BoldItalic TrueType WinAnsi yes yes no 136 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:28:59 CEST RepresentationInformation: pmc_33668473.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:09:03 CEST Size: 712989 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 338 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: How to Measure the Quality of Randomized Clinical Trials Destination: section.1 Children: Item: Title: Rating Quality of Evidence and Strength of Recommendations. Is It Time to Change? Destination: subsection.1.1 Item: Title: Progression-Free Survival Is a Vulnerable Endpoint Destination: subsection.1.2 Item: Title: Concordance between PFS and OS as a Measure of Quality of Clinical Trial Design (QCTD) Destination: subsection.1.3 Item: Title: How to Evaluate Clinical Benefit? Destination: section.2 Children: Item: Title: The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) Destination: subsection.2.1 Item: Title: ASCO Value Framework for Assessing Value in Cancer Care Destination: subsection.2.2 Item: Title: Concordance between ASCO-VF-NHB16 and ESMO-MCBS Destination: subsection.2.3 Item: Title: ASCO-VF and ESMO-MCBS as a Tool to Evaluate Medical Agency Approvals Destination: subsection.2.4 Item: Title: Final Conclusions Destination: section.3 Item: Title: References Destination: figure.caption.7 Info: Title: Are Quality of Randomized Clinical Trials and ESMO-Magnitude of Clinical Benefit Scale Two Sides of the Same Coin, to Grade Recommendations for Drug Approval? Author: Adela Rodriguez, Francis Esposito, Helena Oliveres, Ferran Torres and Joan Maurel Subject: The approval of a new drug for cancer treatment by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) is based on positive, well-designed randomized phase III clinical trials (RCTs). However, not all of them are analyzed to support the recommendations. For this reason, there are different scales to quantify and evaluate the quality of RCTs and the magnitude of the clinical benefits of new drugs for treating solid tumors. In this review, we discuss the value of the progression-free survival (PFS) as an endpoint in RCTs and the concordance between it and the overall survival (OS) as a measure of the quality of clinical trial designs. We summarize and analyze the different scales to evaluate the clinical benefits of new drugs such as the The American Society of Clinical Oncology value framework (ASCO-VF-NHB16) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the concordance between them, focusing on metastatic colorectal cancer (mCRC). We propose several definitions that would help to evaluate the quality of RCT, the magnitude of clinical benefit and the appropriate approval of new drugs in oncology. Keywords: quality randomized studies; ESMO-MCBS; drug approval Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Feb 23 13:01:57 CET 2021 ModDate: Tue Feb 23 13:05:10 CET 2021 ID: 0x821fb01454266def63aae92ad3faf77a, 0x821fb01454266def63aae92ad3faf77a Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: URYLRZ+URWPalladioL-BoldItal FontSubset: true FirstChar: 110 LastChar: 110 FontDescriptor: FontName: URYLRZ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: AEOPJR+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: AEOPJR+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ICRTVP+CMSY10 FontSubset: true FirstChar: 0 LastChar: 20 FontDescriptor: FontName: ICRTVP+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: SDALTV+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: SDALTV+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: DUFXDP+VnURWPalladioL FontSubset: true FirstChar: 161 LastChar: 226 FontDescriptor: FontName: DUFXDP+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: FLNPWT+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: FLNPWT+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 35, 759, 176, 795 Annotation: Subtype: Link Rect: 515, 759, 560, 795 Annotation: Subtype: Link Rect: 138, 641, 149, 654 Annotation: Subtype: Link Rect: 437, 641, 448, 654 Annotation: Subtype: Link Rect: 63, 346, 154, 355 Annotation: Subtype: Link Rect: 35, 334, 75, 343 Annotation: Subtype: Link Rect: 35, 162, 97, 184 Annotation: Subtype: Link Rect: 153, 89, 154, 98 Annotation: Subtype: Link Rect: 35, 77, 147, 86 Annotation: Subtype: Link Rect: 391, 243, 398, 252 ActionDest: 106 Annotation: Subtype: Link Rect: 454, 231, 461, 240 ActionDest: 106 Annotation: Subtype: Link Rect: 193, 193, 200, 202 ActionDest: 106 Annotation: Subtype: Link Rect: 456, 181, 463, 189 ActionDest: 106 Annotation: Subtype: Link Rect: 451, 118, 458, 127 ActionDest: 106 Annotation: Subtype: Link Rect: 318, 80, 325, 89 ActionDest: 106 Annotation: Subtype: Link Rect: 537, 80, 544, 89 ActionDest: 106 Annotation: Subtype: Link Rect: 127, 17, 264, 28 Annotation: Subtype: Link Rect: 422, 17, 558, 28 Annotation: Subtype: Link Rect: 35, 446, 87, 465 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 356, 737, 363, 746 ActionDest: 106 Annotation: Subtype: Link Rect: 549, 561, 556, 570 ActionDest: 106 Annotation: Subtype: Link Rect: 208, 435, 215, 444 ActionDest: 106 Annotation: Subtype: Link Rect: 212, 297, 219, 306 ActionDest: 141 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 247, 534, 259, 543 ActionDest: 141 Annotation: Subtype: Link Rect: 259, 534, 271, 543 ActionDest: 141 Annotation: Subtype: Link Rect: 368, 471, 380, 480 ActionDest: 141 Annotation: Subtype: Link Rect: 198, 383, 210, 392 ActionDest: 141 Annotation: Subtype: Link Rect: 487, 270, 499, 279 ActionDest: 141 Annotation: Subtype: Link Rect: 268, 132, 280, 141 ActionDest: 141 Annotation: Subtype: Link Rect: 280, 132, 292, 141 ActionDest: 141 Annotation: Subtype: Link Rect: 295, 132, 307, 141 ActionDest: 141 Annotation: Subtype: Link Rect: 231, 119, 243, 128 ActionDest: 141 Annotation: Subtype: Link Rect: 243, 119, 255, 128 ActionDest: 141 Annotation: Subtype: Link Rect: 516, 120, 528, 128 ActionDest: 141 Annotation: Subtype: Link Rect: 529, 120, 541, 128 ActionDest: 141 Annotation: Subtype: Link Rect: 544, 119, 556, 128 ActionDest: 141 Annotation: Subtype: Link Rect: 425, 94, 437, 103 ActionDest: 141 Annotation: Subtype: Link Rect: 438, 94, 450, 103 ActionDest: 141 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 531, 722, 543, 731 ActionDest: 141 Annotation: Subtype: Link Rect: 544, 722, 556, 731 ActionDest: 141 Annotation: Subtype: Link Rect: 381, 683, 388, 694 ActionDest: 80 Annotation: Subtype: Link Rect: 75, 563, 86, 571 ActionDest: 141 Annotation: Subtype: Link Rect: 77, 547, 88, 555 ActionDest: 141 Annotation: Subtype: Link Rect: 80, 531, 91, 540 ActionDest: 141 Annotation: Subtype: Link Rect: 77, 499, 88, 507 ActionDest: 141 Annotation: Subtype: Link Rect: 71, 467, 82, 475 ActionDest: 141 Annotation: Subtype: Link Rect: 78, 451, 89, 460 ActionDest: 141 Annotation: Subtype: Link Rect: 72, 430, 83, 438 ActionDest: 141 Annotation: Subtype: Link Rect: 303, 318, 310, 327 ActionDest: 106 Annotation: Subtype: Link Rect: 530, 318, 537, 327 ActionDest: 106 Annotation: Subtype: Link Rect: 193, 302, 200, 315 ActionDest: 91 Annotation: Subtype: Link Rect: 529, 293, 541, 302 ActionDest: 141 Annotation: Subtype: Link Rect: 544, 293, 556, 302 ActionDest: 145 Annotation: Subtype: Link Rect: 271, 252, 278, 264 ActionDest: 91 Annotation: Subtype: Link Rect: 90, 159, 101, 168 ActionDest: 141 Annotation: Subtype: Link Rect: 82, 138, 93, 146 ActionDest: 141 Annotation: Subtype: Link Rect: 84, 117, 95, 125 ActionDest: 141 Annotation: Subtype: Link Rect: 88, 101, 99, 109 ActionDest: 141 Annotation: Subtype: Link Rect: 90, 80, 100, 88 ActionDest: 145 Annotation: Subtype: Link Rect: 97, 58, 108, 67 ActionDest: 141 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 92, 693, 103, 702 ActionDest: 141 Annotation: Subtype: Link Rect: 92, 672, 103, 681 ActionDest: 145 Annotation: Subtype: Link Rect: 95, 657, 106, 665 ActionDest: 141 Annotation: Subtype: Link Rect: 83, 641, 94, 649 ActionDest: 145 Annotation: Subtype: Link Rect: 80, 625, 91, 633 ActionDest: 141 Annotation: Subtype: Link Rect: 92, 609, 103, 618 ActionDest: 145 Annotation: Subtype: Link Rect: 94, 593, 105, 602 ActionDest: 145 Annotation: Subtype: Link Rect: 89, 572, 100, 581 ActionDest: 145 Annotation: Subtype: Link Rect: 445, 139, 457, 148 ActionDest: 145 Annotation: Subtype: Link Rect: 458, 139, 470, 148 ActionDest: 145 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 510, 232, 522, 241 ActionDest: 145 Annotation: Subtype: Link Rect: 522, 232, 534, 241 ActionDest: 145 Annotation: Subtype: Link Rect: 519, 69, 526, 78 ActionDest: 106 Annotation: Subtype: Link Rect: 529, 69, 536, 78 ActionDest: 106 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 501, 584, 513, 593 ActionDest: 145 Annotation: Subtype: Link Rect: 516, 584, 528, 593 ActionDest: 145 Annotation: Subtype: Link Rect: 376, 446, 388, 455 ActionDest: 145 Annotation: Subtype: Link Rect: 389, 446, 401, 455 ActionDest: 145 Annotation: Subtype: Link Rect: 404, 446, 416, 455 ActionDest: 145 Annotation: Subtype: Link Rect: 454, 443, 461, 455 ActionDest: 97 Annotation: Subtype: Link Rect: 90, 261, 101, 269 ActionDest: 145 Annotation: Subtype: Link Rect: 79, 245, 90, 253 ActionDest: 145 Annotation: Subtype: Link Rect: 80, 229, 91, 238 ActionDest: 145 Annotation: Subtype: Link Rect: 91, 214, 102, 222 ActionDest: 145 Annotation: Subtype: Link Rect: 516, 126, 523, 138 ActionDest: 100 Annotation: Subtype: Link Rect: 348, 75, 355, 87 ActionDest: 103 Annotation: Subtype: Link Rect: 511, 65, 523, 75 ActionDest: 145 Annotation: Subtype: Link Rect: 526, 65, 538, 75 ActionDest: 148 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 390, 669, 397, 681 ActionDest: 106 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 101, 417, 111, 424 ActionDest: 145 Annotation: Subtype: Link Rect: 101, 383, 111, 391 ActionDest: 148 Annotation: Subtype: Link Rect: 102, 345, 112, 353 ActionDest: 148 Annotation: Subtype: Link Rect: 75, 279, 84, 287 ActionDest: 148 Annotation: Subtype: Link Rect: 105, 241, 115, 249 ActionDest: 148 Annotation: Subtype: Link Rect: 102, 213, 112, 220 ActionDest: 148 Annotation: Subtype: Link Rect: 102, 165, 112, 173 ActionDest: 148 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 314, 273, 352, 284 Annotation: Subtype: Link Rect: 464, 250, 502, 261 Annotation: Subtype: Link Rect: 395, 227, 432, 238 Annotation: Subtype: Link Rect: 438, 227, 474, 238 Annotation: Subtype: Link Rect: 118, 193, 155, 203 Annotation: Subtype: Link Rect: 161, 193, 197, 203 Annotation: Subtype: Link Rect: 242, 169, 279, 180 Annotation: Subtype: Link Rect: 486, 158, 524, 169 Annotation: Subtype: Link Rect: 59, 78, 97, 88 Annotation: Subtype: Link Rect: 103, 78, 139, 88 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 479, 721, 516, 732 Annotation: Subtype: Link Rect: 521, 721, 557, 732 Annotation: Subtype: Link Rect: 470, 698, 507, 709 Annotation: Subtype: Link Rect: 249, 664, 286, 674 Annotation: Subtype: Link Rect: 422, 640, 459, 651 Annotation: Subtype: Link Rect: 282, 594, 319, 605 Annotation: Subtype: Link Rect: 326, 594, 362, 605 Annotation: Subtype: Link Rect: 273, 572, 311, 582 Annotation: Subtype: Link Rect: 59, 538, 97, 548 Annotation: Subtype: Link Rect: 519, 514, 557, 525 Annotation: Subtype: Link Rect: 59, 503, 95, 513 Annotation: Subtype: Link Rect: 319, 469, 356, 479 Annotation: Subtype: Link Rect: 362, 469, 398, 479 Annotation: Subtype: Link Rect: 372, 445, 410, 456 Annotation: Subtype: Link Rect: 212, 423, 250, 433 Annotation: Subtype: Link Rect: 256, 423, 292, 433 Annotation: Subtype: Link Rect: 171, 388, 209, 398 Annotation: Subtype: Link Rect: 145, 354, 182, 364 Annotation: Subtype: Link Rect: 313, 318, 351, 329 Annotation: Subtype: Link Rect: 357, 318, 393, 329 Annotation: Subtype: Link Rect: 59, 273, 97, 283 Annotation: Subtype: Link Rect: 103, 273, 139, 283 Annotation: Subtype: Link Rect: 260, 238, 297, 249 Annotation: Subtype: Link Rect: 262, 204, 299, 214 Annotation: Subtype: Link Rect: 305, 204, 341, 214 Annotation: Subtype: Link Rect: 254, 157, 291, 168 Annotation: Subtype: Link Rect: 189, 123, 227, 134 Annotation: Subtype: Link Rect: 233, 123, 269, 134 Annotation: Subtype: Link Rect: 520, 88, 557, 99 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 488, 710, 525, 720 Annotation: Subtype: Link Rect: 104, 676, 141, 686 Annotation: Subtype: Link Rect: 104, 641, 141, 651 Annotation: Subtype: Link Rect: 450, 606, 488, 617 Annotation: Subtype: Link Rect: 59, 572, 97, 582 Annotation: Subtype: Link Rect: 103, 572, 139, 582 Annotation: Subtype: Link Rect: 59, 526, 97, 536 Annotation: Subtype: Link Rect: 103, 526, 139, 536 Annotation: Subtype: Link Rect: 167, 492, 204, 502 Annotation: Subtype: Link Rect: 211, 492, 247, 502 Annotation: Subtype: Link Rect: 435, 457, 472, 467 Annotation: Subtype: Link Rect: 478, 457, 514, 467 Annotation: Subtype: Link Rect: 332, 422, 370, 433 Annotation: Subtype: Link Rect: 158, 388, 196, 398 Annotation: Subtype: Link Rect: 520, 364, 557, 375 Annotation: Subtype: Link Rect: 520, 330, 557, 341 Annotation: Subtype: Link Rect: 59, 319, 95, 329 Annotation: Subtype: Link Rect: 458, 295, 495, 306 Annotation: Subtype: Link Rect: 417, 272, 454, 283 Annotation: Subtype: Link Rect: 225, 238, 262, 249 Annotation: Subtype: Link Rect: 269, 238, 305, 249 Annotation: Subtype: Link Rect: 477, 203, 514, 214 Annotation: Subtype: Link Rect: 521, 203, 557, 214 Annotation: Subtype: Link Rect: 480, 180, 517, 191 Annotation: Subtype: Link Rect: 59, 146, 97, 157 Annotation: Subtype: Link Rect: 103, 146, 139, 157 Annotation: Subtype: Link Rect: 100, 112, 137, 122 Annotation: Subtype: Link Rect: 515, 88, 553, 99 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 511, 709, 548, 720 Annotation: Subtype: Link Rect: 369, 617, 407, 628 Annotation: Subtype: Link Rect: 180, 572, 217, 582 Annotation: Subtype: Link Rect: 223, 572, 259, 582 Annotation: Subtype: Link Rect: 193, 538, 230, 548 Annotation: Subtype: Link Rect: 237, 538, 273, 548 Annotation: Subtype: Link Rect: 519, 503, 557, 513 Annotation: Subtype: Link Rect: 59, 492, 95, 502 Checksum: 4839d581 Type: CRC32 Checksum: 1e7ed2bc5b0df1b36cfb396dd13e2022 Type: MD5 Checksum: a9bfcda31a6277f4695372b47d4a90ceef2f38bb Type: SHA-1 Checksum: 283668dd925433cc8b6a6320232a5a43f1e9a18ee8d86becd7a8aa0312464ed8 Type: SHA-256