Followers | 228 |
Posts | 14852 |
Boards Moderated | 1 |
Alias Born | 03/29/2014 |
![](https://investorshub.advfn.com/uicon/467032.png?cb=1478627184)
Sunday, July 14, 2024 2:01:53 PM
Adjustment for Individual Patient Characteristics in ECPs
A fourth set of analyses was conducted to adjust for differences in the individual patient characteristics in the DCVax-L cohort vs. the ECPs. Propensity score matching could not be used because the ECP data were not accessible on a patient-by- patient basis, despite efforts to obtain such data. However, the percentages of specific patient characteristics were available for the ECP. Accordingly, we used Matching-Adjusted Indirect Comparison (MAIC) methodology (widely used in health economic analyses) to adjust for even small differences and re-assess survival outcomes6-8. This methodology applies a weight to each individual patient in the DCVax-L population in such a way that the sum of the weights for patients in each category for a characteristic achieves a match with the external control population. By way of example, if the external population included 50 males and 50 females and the DCVax-L population included 60 males and 40 females, the males would need to be down-weighted to achieve the required 50:50 balance. Applying a weight of 0.67 to each individual male and a weight of 1 to each individual female would achieve that balance, resulting in a new population with effectively 40 males and 40 females. When there are several characteristics to be matched (simultaneously), the mathematics by which the weights are applied to individual patients becomes more complex.
This matching was done on the characteristics of age, sex, race, MGMT methylation status, and KPS score, combined with one of either extent of resection or with residual disease. The MAIC weights required to adjust the DCVax-L cohort to match the characteristics of the external comparators were calculated in the statistical program ‘R’. These weights were checked to ensure that the characteristics of the re-weighted DCVax-L population matched those of the ECP, as well as for any outliers (particularly large weights) that could strongly influence the results of the analysis. Results between the unweighted and weighted (or matched) analyses were compared to confirm the results.
Also, please note... there were three additional analyses used:
1. Matched Comparator Studies for External Comparator Populations (ECP)
The nGBM and rGBM ECPs were determined by an independent expert firm (York Health Economics Consortium), and were comprised of patient data from the control arms of contemporaneous formal RCTs closely matched to the current study based on 14 criteria pre-specified in the SAP (7 for nGBM and 7 for rGBM). For nGBM the criteria included: 1) contemporaneous study time period; 2) reported outcomes (including survival); 3) same standard of care used (radiation and
temozolomide); 4) randomized study design; 5) patients aged >18; 6) KM curves available for survival and for subgroups; and 7) publication in English. The criteria for rGBM at first recurrence were similar., with one difference being that lomustine, bevacizumab or best supportive care were allowed as treatment for the control arms. Based on these criteria, 5 RCTs for nGBM and 10 RCTs for rGBM were matched to our study, and were designated as the ECPs in our SAP (eTable 1). These studies also met the “fit for purpose” criteria outlined by Mishra-Kalyani, et al.1 . The studies that contributed to the ECP provided high quality survival data, with overall lost to follow-up (ltfu) rates of 2% or less (except one study2 that had an ltfu rate of 6%). Similarly, the DCVax-L study had less than 2% of patients lost to follow-up.
2. Validation of the ECP Approach
To further validate the accuracy of the approach and rule out false positive results, each RCT comparator study was evaluated using the same [pooled] ECP that served as the control for the DCVax-L study, instead of using the original control arm in that RCT comparator study, in order to determine whether using this ECP would have changed the outcome originally reported (i.e., primary endpoint met or unmet). This analysis showed that the RCTs that originally failed to show statistically significant survival benefit also failed to show significant survival benefit when the treatment arm of the RCT was compared to our pooled ECP instead of to the original RCT controls, and the one RCT that had a positive outcome was also positive under this ECP approach.
3. Sensitivity Analyses
Although the ECP comparator studies were closely matched with the current study, small non-significant differences could potentially impact outcomes. To address this and further validate the nGBM ECP, we conducted 5 sensitivity analyses, removing each of the 5 comparator studies from the ECP, one at a time. We also conducted a 6th sensitivity analysis, removing 2 of the 5 nGBM comparator trials3, as it was unclear whether they excluded patients with early progression at the time of enrollment, as was done in our study and in 3 of the 5 comparators2,4,5.
https://cdn.jamanetwork.com/ama/content_public/journal/oncology/939074/coi220066supp2_prod_1674054620.80505.pdf?Expires=1723969269&Signature=upcw0yGHuhr3QjYaug7VkxKQ2OCQ2zAuqQJjGgRsCcrew5SKzUHDRRzA6mdDNA6FG3qY8CCazgAdqdFe6BHxuZhQn5QkjC3XBquNybj7HQ7epRJLj5VtvzfsoTLr9OR9iph5dtmCZAPI6QaHI3qYXoZscHX0IHGIiUxzc8Sudfe1p68DCxQbK38865Ajq8cDkmTEPp21zNPJNQt2kChQLI-OtWv0HS4h0u~wjQOLK9SxbqmccmFLeC-OVnjb66DtsClG1ia61BYKicL8cKlfrXSE1kGbPBY8npfDu6xFOW073cVYO-XuVHCQnHT-f6EkVen84zmzUAViPxFQXEHNVQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
All of these additional methods will hopefully prove satisfactory to overcoming any qualms about not having had access to the patient level data that would have had to have been supplied by competing companies (lol).
So there's (all) that, which should help to satisfy the scientific minds in control of approvals, even if it doesn't satisfy those greedy little hedge fund minds.
Recent NWBO News
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 09/03/2024 08:01:40 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 08/13/2024 08:01:24 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 08/09/2024 09:06:07 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 08/08/2024 08:30:09 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 08/02/2024 02:42:28 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 07/30/2024 11:49:38 PM
- Biophma Announces Exclusive In License for Dendritic Cell Technology, Sending Shares Higher • AllPennyStocks.com • 06/17/2024 04:40:00 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 06/04/2024 09:11:16 PM
- Form DEF 14A - Other definitive proxy statements • Edgar (US Regulatory) • 06/03/2024 09:22:55 PM
- Form PRE 14A - Other preliminary proxy statements • Edgar (US Regulatory) • 05/22/2024 08:13:36 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 05/10/2024 09:04:57 PM
- Form NT 10-K - Notification of inability to timely file Form 10-K 405, 10-K, 10-KSB 405, 10-KSB, 10-KT, or 10-KT405 • Edgar (US Regulatory) • 03/01/2024 10:04:38 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 12/02/2023 01:31:35 AM
- Form 8-K - Current report • Edgar (US Regulatory) • 11/16/2023 10:11:54 PM
- Epazz, Inc. (OTC Pink: EPAZ) ZenaDrone Demonstration to Defense Departments of UAE and Saudi Arabia • InvestorsHub NewsWire • 11/15/2023 12:19:31 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 11/09/2023 09:30:39 PM
- Epazz, Inc. (OTC Pink: EPAZ) US Navy Collaboration ZenaDrone 1000 • InvestorsHub NewsWire • 11/09/2023 01:00:34 PM
- Epazz, Inc. (OTC Pink: EPAZ) US Navy Collaboration ZenaDrone 1000 Extreme Weather Demo • InvestorsHub NewsWire • 11/07/2023 12:29:43 PM
FEATURED Element79 Gold Corp. Announces Sale of 100% Interest in Elder Creek, North Mill Creek, and Elephant Projects to 1472886 B.C. Ltd. • Sep 9, 2024 9:34 AM
Nightfood Holdings Inc. Completes Major Step on Uplist Journey by Closing Strategic All-Stock Acquisition of CarryoutSupplies.com • NGTF • Sep 10, 2024 8:15 AM
North Bay Resources Commences Gold Shipments, Fran Gold Project, British Columbia; Enters Taber Gold Mine JV, Sierra County, California • NBRI • Sep 9, 2024 9:15 AM
Simple Stock Loans Announces Unique Solutions For Investors Looking for Alternative Liquidity Amidst Recent Small Cap Rally Sep 6, 2024 9:30 AM
Reliant Coffee Debuts at #271 on the Inc. 5000 List of Fastest Growing Companies - Coffee Service Industry Disruptor Brews Up Exponential Growth Sep 5, 2024 11:51 AM
VAYK Confirms Receiving Revenue from First Airbnb Property with 1.4 Million Annual Revenue Goal • VAYK • Sep 4, 2024 9:34 AM