Category: 3. Business

  • Thames Water: advisers appointed to plan for company’s potential collapse | Water industry

    Thames Water: advisers appointed to plan for company’s potential collapse | Water industry

    UK ministers have appointed insolvency advisers to make contingency plans for the potential collapse of Thames Water.

    The company, which supplies 16 million customers, has been racing to pull together a deal to avoid financial collapse.

    In a development first reported by Sky News, Steve Reed, the environment secretary, has signed off the appointment of FTI Consulting to advise on plans for Thames Water to be placed into a special administration regime (SAR).

    The appointment indicates that FTI is the frontrunner to act as administrator if the government enacted an SAR, although a court would ultimately approve such a step.

    The government has been trying to avoid such an outcome, with the Treasury threatening that a potential £4bn bill from the SAR could be forced on to Reed’s department. This process would ensure that the taps stayed on for customers but would heap immediate costs on to the government.

    However, the government’s Water (Special Measures) Act contains a provision for SAR costs to be recouped from customer bills further down the line.

    Thames faced embarrassment earlier this year when its preferred bidder, KKR, pulled out of a deal at the last minute. Now, its class A creditors, who hold the bulk of the company’s senior debt, are in talks with the regulator, Ofwat, about a deal to inject capital into the company, which has £17.7bn of net debts and regulatory gearing of 84.4%.

    The company has been trying to get Ofwat to write off more than £1bn in expected fines from failures to invest in infrastructure to stop sewage spills, in order to secure a rescue deal. Chris Weston, chief executive of Thames Water, told a recent parliament committee that the company could not afford to pay these fines and continue to invest and operate as was expected by the regulator.

    A company spokesperson said: “Our focus remains on a holistic and fundamental recapitalisation, delivering a market-led solution, which includes targeting investment-grade credit ratings and returning the company to a stable financial foundation.

    “Constructive discussions with our many stakeholders continue.”

    Andy Prendergast, national secretary of the GMB union, said: “Thames Water has been sacrificed on the altar of privatisation. It’s sinking without a trace under a deluge of debt, while huge amounts of cash from inflated customer bills have flooded out to directors, shareholders and loan servicing.

    “If you want an advert for why private companies shouldn’t be involved in certain sectors, this is it. Yet another damning indictment of Thatcher’s terrible legacy.

    “The government must now intervene to find a water-tight solution that protects Thames’ millions of customers and gives immediate guarantees for the thousands of loyal workers and their pensions.”

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    Thames Water faced fury recently over plans to pay senior staff members millions in bonuses from a controversial £3bn loan granted by the class A creditors. The company has been banned from paying performance-related bonuses to its chief executive and chief financial officer because of its poor performance.

    A government spokesperson said: “The government will always act in the national interest on these issues.

    “The company remains financially stable, but we have stepped up our preparations and stand ready for all eventualities, including applying for a special administration regime if that were to become necessary.”

    FTI Consulting declined to comment.

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  • Ireland on watch as UKIPO prepares to drop ‘series’ trade marks

    Ireland on watch as UKIPO prepares to drop ‘series’ trade marks

    The UK Intellectual Property Office (UKIPO) will stop accepting series mark applications from the end of this year, bringing it in line with the European Intellectual Property Office (EUIPO).

    Currently companies in the UK can file six variations of a trademark with non-distinctive changes – such as colours – as part of the same application and have to pay only one application fee for this, but the rules are set to be streamlined within the next few months.

    Maureen Daly, an IP law expert and partner at Pinsent Masons, said the move would widen the IP regulation gap between the UK and Ireland.

    “While series applications can be tricky as they can give rise to objections if they are not properly drafted, they do provide brand owners – particularly SMEs – with flexibility as well as costs savings,” said Daly

    “This new development further sets the UK apart from Ireland.”

    The changes come as UKIPO looks to simplify the registration process for trade marks, with the current series mark system – which allow for up to six changes that do not substantially change the identity of the mark, such as colours or minor spelling variations – but this has created potential delays for filings over confusion as to what counts as a series.

    While the EUIPO does not allow series marks, Ireland’s national trade mark system currently does – but Daly warned that this may change depending on how reaction to the UK’s shift in approach lands with users of the service.

    She added: “While the Irish IP Office has not announced any plans to remove series marks, Irish businesses and legal advisors should monitor this because if the UK experience shows minimal negative impact, the Irish IP Office might consider adopting a similar move in the future.”

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  • Effect of High-Flow Nasal Oxygen Versus Conventional Oxygen Therapy on Postoperative Atelectasis in Obese Cardiac Surgical Patients: Randomized Controlled Trial

    Effect of High-Flow Nasal Oxygen Versus Conventional Oxygen Therapy on Postoperative Atelectasis in Obese Cardiac Surgical Patients: Randomized Controlled Trial


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  • India markets regulator looks to further ease regulations for foreign investors – Reuters

    1. India markets regulator looks to further ease regulations for foreign investors  Reuters
    2. Sebi comes bearing GIFT, moots steps to boost resident Indian participation in FPIs  The Economic Times
    3. SEBI Proposal: Domestic investors may get access to FPIs in IFSC  Zee Business
    4. India’s SEBI looking to simplify foreign investor regulations to boost capital By Investing.com  Investing.com
    5. SEBI seeks feedback on expanding FPI access for Indian investors  Prop News Time

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  • Alectinib Efficacy Post-Brigatinib Against Advanced ALK+ Non-Small Cel

    Alectinib Efficacy Post-Brigatinib Against Advanced ALK+ Non-Small Cel

    Renaud Descourt,1 Florian Guisier,2 Maurice Pérol,3 Jacques Cadranel,4 Helene Doubre,5 Michael Duruisseaux,6– 8 Stéphane Culine,9 Bertrand Mennecier,10 Olivier Bylicki,11 Christos Chouaid,12 Laurent Greillier13

    1Hopital La Cavale Blanche, CHU Brest, Brest, France; 2CHU Rouen, Rouen, France; 3CLCC Léon-Bérard, Lyon, France; 4Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Paris, France; 5Hôpital Foch, Suresnes, France; 6Department of Respiratory Medicine and Early Phase (EPSILYON), Louis Pradel Hospital, Hospices Civils de Lyon Cancer Institute, Lyon, France; 7Oncopharmacology Laboratory, Cancer Research Centre of Lyon, UMR INSERM 1052 CNRS 5286, Lyon, France; 8Claude Bernard University Lyon 1, University of Lyon, Lyon, France; 9Hôpital Saint-Louis, Assistance Publique des Hôpitaux de Paris, Paris, France; 10CHU Nancy, Nancy, France; 11HIA Sainte-Anne, Toulon, France; 12CHI Créteil, Créteil, France; 13Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Aix–Marseille Université, Marseille, France

    Correspondence: Renaud Descourt, Oncology department, Cavale Blanche Hospital, Brest University Hospital, Boulevard Tanguy-Prigent, Brest, 29200, France, Email [email protected]

    Background: Brigatinib and alectinib are next-generation anaplastic lymphoma kinase inhibitors (ALKis) showing efficacy against naïve and post-crizotinib-treated advanced ALK+ non-small-cell lung cancers (NSCLCs). Real-world data on alectinib efficacy after brigatinib failure are lacking.
    Methods: Alectinib efficacy was retrospectively assessed in patients previously treated with brigatinib during an early-access program (EAP) from 1 August 2016 to 21 January 2019. The primary endpoint was alectinib median progression-free survival (mPFS) according to local investigators.
    Results: Among the 183 patients included in the brigatinib EAP, 92 (50.3%) received ≥ 1 agent(s) post-brigatinib; 30 (16.4%) received alectinib, 19 (10.4%) immediately post-brigatinib; 11 (6%) after ≥ 1 other treatment line(s). With median follow-up at 25.5 (95% CI: 10.6– 30.5) months, mPFS on brigatinib for the study population (n = 30) was 13.6 (95% CI: 6.3– 17.7) months. For patients given alectinib immediately post-brigatinib, mPFS and median overall survival (mOS) were 4.8 (95% CI: 2.0– 12.5) and 27 (95% CI: 12.5–not reached (NR)) months, respectively. In this subgroup, brigatinib was discontinued for toxicity or progression for 5/19 (26%) or 14/19 (74%) patients, with mPFS lasting 12.5 (95% CI: 3.3– 17.9 and 3.4 (95% CI: 0.9– 9.2) months, respectively. For patients receiving ≥ 1 agent(s) between brigatinib and alectinib, with median follow-up at 13.3 (95% CI: 2.3– 31.5) months, mPFS and mOS were 5.0 (95% CI: 0.5– 18.8) and 19 (95% CI: 2.3–NR) months, respectively.
    Conclusion: According to the results of this retrospective real-world study, alectinib post-brigatinib showed limited overall activity but remains an option for patients with advanced ALK+ NSCLCs, especially when brigatinib was discontinued because of toxicity.

    Introduction

    Brigatinib and alectinib are second-generation anaplastic lymphoma kinase inhibitors (ALKis) and both are used as first-line standard-of-care for advanced ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC) based on the results of two randomized Phase 3 trials.1 The ALTA-1L trial compared brigatinib vs crizotinib as first-line therapy for ALK+ NSCLC; brigatinib significantly prolonged median progression-free survival (mPFS), the primary endpoint, from 11.1 to 24 months, according to the Blinded Independent Review Committee (BIRC) (HR: 0.48 [95% CI: 0.35–0.66]; p < 0.0001), with respective 3- and 4-year mPFS rates of 43% and 36%.2 The ALEX trial that compared alectinib vs crizotinib as first-line therapy for ALK+ NSCLC, also found mPFS to be significantly prolonged with alectinib (25 vs 11.1 months according to BIRC; HR: 0.50 [95% CI: 0.36–0.70]; p < 0.0001), with respective 3- and 4-year mPFS rates of 46.4% and 43.7%.3

    In the management of ALK-rearranged NSCLC, several studies, especially in real-world conditions, have demonstrated the positive prognostic impact of the therapeutic sequence.4,5 With this in mind, we have already made a focus on post-brigatinib lorlatinib efficacy in the real-world BrigALK2 study.6 Another interesting sequence is post-brigatinib alectinib efficacy for which data are scarce.

    BrigALK2 is a French, multicenter, retrospective, real-world study that evaluated brigatinib efficacy prescribed in an early-access program (EAP) in France, from 1 August 2016 to 21 January 2019. It enrolled 183 patients with pre-treated advanced ALK+ NSCLCs. For those heavily treated patients (median of two ALKis before brigatinib), mPFS and median overall survival (mOS) from brigatinib initiation were, respectively, 7.4 and 20.3 months.6

    The aim of this ancillary analysis was to assess alectinib efficacy when administered after brigatinib to patients with advanced ALK+ NSCLCs in a real-world setting.

    Patients and Methods

    Study Design and Patients

    As previously described, patients included in the BrigALK2 trial had advanced, ALK-rearranged NSCLC pre-treated with at least one ALKi, and had received brigatinib as part of its early access in France between August 1, 2016, and January 21, 2019. This analysis focused on alectinib efficacy post-brigatinib failure (toxicity or progressive disease). Patients were identified and included by each local investigator in participating centers. Alectinib could have been prescribed immediately post-brigatinib or after at least one other line of therapy.

    Data Collection

    Patient information, retrospectively collected from medical records and entered into a case-report form, included demographics and NSCLC characteristics, numbers and localizations of metastatic sites, numbers of previous treatments, reason for brigatinib discontinuation (progression or toxicity), therapeutic sequences, if any, between brigatinib and alectinib, and treatments after alectinib. All identified eligible patients were enrolled, without selection, in each participating center.

    Endpoints

    The primary endpoint was mPFS on alectinib, according to local investigators, defined as the time between alectinib onset and progression or death. Secondary endpoints were median duration of treatment (mDOT), mOS from alectinib onset, disease-control rate (DCR) and objective response rate (ORR). Each endpoint was evaluated according to therapeutic sequence, either alectinib initiation immediately post-brigatinib (brigatinib-alectinib) or after at least one intermediate line (chemotherapy or ALKi; brigatinib-X-alectinib).

    Statistical Analyses

    Patient characteristics were compared with a chi-square test or Fisher’s exact test for discrete variables. The Kaplan–Meier method was used to estimate PFS, DOT and OS for the entire population, subgroups defined by their therapeutic sequences and reason for brigatinib discontinuation. The Log rank test compared survival according to treatment sequence. Responses to treatment were assessed by local investigators applying RECIST 1.1 criteria. Statistical analyses were computed with SAS v9.4 software (SAS Institute, Cary, NC, USA).

    The study was conducted in accordance with French laws and regulations in force (law 78–17 of 6 January 1978 modified by laws 94–548 of 1 July 1994, 2002–303 of 4 March 2002, 2004–801 of 6 August 2004). The GFPC has committed to the French National Commission for Data Protection and Liberties (CNIL) to respect MR-004 reference methodology.

    Results

    During the brigatinib EAP, 183 patients managed in 66 centers were enrolled. At data cut-off date (7 July 2022), 92 (50.3%) patients had received at least one agent(s) post-brigatinib (ALKi or chemotherapy); 30 (16.4%) who received alectinib post-brigatinib—regardless of treatment line—constituted the study population (Figure 1). Median age was 53 years, and all NSCLCs had adenocarcinoma histology. Patients were heavily pre-treated with a median of four therapeutic lines before alectinib, receiving a median of three ALKis (Table 1). Under brigatinib, mPFS and mDOT were 13.6 (95% CI: 6,3–17,7) and 10.9 (95% CI: 6,2–20,2) months, respectively. Brigatinib was discontinued because of progression for 22 (73.3%) patients and toxicity for 8 (26.7%). Under brigatinib, the main progression site was the brain (71%), including 20% of patients with carcinomatous meningitis as progression.

    Table 1 Patients Characteristics

    Figure 1 Flowchart.

    Figure 2 Median overall survival curve for patients treated with the brigatinib-alectinib sequence (n=19).

    Figure 3 Median overall survival curve for patients treated with the brigatinib-X-alectinib sequence (n=11).

    Among the 30 patients, 19 (63%) received alectinib immediately post-brigatinib and 11 (37%) after at least one other chemotherapy or ALKi line (Figure 1).

    After median follow-up of 25.5 (95% CI: 10.6–30.5) months, brigatinib-alectinib–sequence patients’ mPFS and mOS were 4.8 (95% CI: 2.0–12.5) and 27.0 (95% CI: 12.5–not reached (NR)) months, respectively (Figure 2); alectinib ORR was 26.3% (5/19) with no complete responses, DCR was 63% and mDOT, 7.1 (95% CI: 2.1–18.2) months. For patients who discontinued brigatinib because of treatment-related adverse event(s)/toxicity, mPFS and mDOT lasted 12.5 (95% CI: 3.3–17.9) and 18.2 (95% CI: 3.4–21.6) months, respectively, vs 3.4 (95% CI: 0.9–9.2) and 5.7 (95% CI: 0.9–10.6) months for those who stopped brigatinib because of progression (Table 2).

    Table 2 Alectinib Efficacy Post-Brigatinib Failure According to Sequence

    For patients treated with alectinib after at least one other treatment line post-brigatinib, mPFS and mDOT were 5.0 (95% CI: 0.5–18.8) and 11.7 (95% CI: 0.7–21.5) months, respectively, mOS was 19.0 (95% CI: 2.3–NR) months (Figure 3) with ORR of 10% and DCR of 30% (Table 2).

    Discussion

    In this multicenter population of EAP patients with heavily pre-treated advanced ALK+ NSCLCs, alectinib immediately post-brigatinib showed limited overall activity with respective mPFS and mDOT of 4.8 and 7.1 months. Those durations, respectively, were dependent on whether brigatinib was discontinued for toxicity (12.5 and 18.2 months) or progression (3.4 and 5.7 months).

    Published data on post-brigatinib alectinib efficacy against advanced ALK+ NSCLCs are scarce. ALTA-L1-trial results of second-line ALKi, after progression on first-line brigatinib were reported recently. In that post hoc analysis, 40 patients received treatment post-brigatinib, an ALKi for 30, including alectinib for 8 of them.7 For the latter patients given the brigatinib-alectinib sequence, after a median follow-up of 17 months, mPFS and time to treatment discontinuation were 16.1 months and NR, respectively. The considerable difference between those results and ours can probably be explained by our patients having been heavily pre-treated, with a median of three ALKis before alectinib. Reasons for brigatinib discontinuation in the ALTA-L1 trial were not specified, whereas our results revealed very different efficacy profiles depending on whether patients stopped brigatinib because of toxicity or progression.

    To our knowledge, very few studies have examined the therapeutic sequences and efficacy of ALKi according to the cause of discontinuation, progression or toxicity. This seems to be the most important point to emerge from our analyses, all things being equal, of course, as this is a retrospective study with few patients in the analyses carried out. Such data are addressed in the CROWN trial, in the analysis of post-first-line treatments.8

    CROWN has recently revolutionized first-line management of ALK+ stage 4 NSCLC. Previously, lorlatinib was the standard second line TKI in cases of progression with first line alectinib or brigatinib, based on clinical trial7,9 and real-world data.10 More recently, CROWN trial demonstrated lorlatinib superiority over crizotinib as first-line therapy. A post-hoc analysis with 5 years of follow-up showed that the mPFS was NR on lorlatinib (NR [95% CI: 64.3–NR]) and 9.1 months [95% CI: 7.4–19] with crizotinib (HR: 0.19. [95% CI: 0.13–0.27], with respective 5-year mPFS rates of 60% vs 8%.11 Those findings clearly established lorlatinib as a first-line therapy option, but no direct comparison was made with a second-generation ALKi and, thus, the optimal sequence choice is not yet evident. Management after progression on first-line lorlatinib was reported in a CROWN-trial update: 33/149 (22.1%) patients received second-line therapy: 21/33 (63.6%) patients another ALKi, usually alectinib (12/21, 57.1%). On a first ALKi as subsequent post-lorlatinib therapy, mDOT was 9.6 months. Swimmer plots of data tended to show that patients benefiting the most from another ALKi were those who discontinued lorlatinib because of toxicity. Those preliminary data must be confirmed with future CROWN trial updates. Although the brigatinib-alectinib sequence has been poorly studied specifically, switching from one second-generation ALKi to another has been evaluated with other molecules. A single-arm, prospective, Phase II trial on 103 patients who had received a maximum of three treatment lines examined brigatinib efficacy after progression on ceritinib or alectinib.12 Those authors found disappointing clinical activity: ORR of 26.2%, and respective mPFS and mDOT of 3.8 and 6.3 months. Lin et al retrospectively analyzed 22 patients with alectinib-refractory advanced ALK+ NSCLCs in a multicenter population.13 Most of those patients had received brigatinib immediately after alectinib. That strategy had limited efficacy, with PFS at 4.4 months and ORR of 17%. All those studies analyzed second-generation ALKi efficacy in the event of progression, whereas, notably, our study results showed greater efficacy in patients who had discontinued brigatinib because of toxicity.

    The data available for our study population did not allow us to analyze the resistance mechanisms at progression on brigatinib. Such investigations were not routine practice when the brigatinib EAP was ongoing. However, identification of a resistance mutation at disease progression might help adapt subsequent treatments. Unfortunately, information on ALKi activity according to resistance mechanisms determined on rebiopsy specimens obtained at progression are limited and derived from retrospective series. For example, Lin et al had those data for only 9 patients, with tissue or liquid biopsies obtained at progression on alectinib.13 A resistance mutation was found in 6/9 (66.7%) specimens and theoretical brigatinib-susceptibility mutations were found in 5/6 (83.3%) samples. On brigatinib, one patient had a partial response or progressed and three achieved stable disease.

    Our study has several limitations. First is its retrospective design without data monitoring. Treatment assessment was not centralized, so local investigator-assessment bias cannot be excluded. In this real-world study, alectinib efficacy was evaluated in heavily pre-treated patients having received a median of four previous lines. Therefore, we cannot rule out a potential immortality time bias that limits interpretation of the results obtained. However, one of the strengths of this study is the absence of stringent criteria for study inclusion, meaning that the population is representative of real-world, heavily treated patients with advanced ALK+ NSCLCs.14

    Conclusion

    According to the results of our retrospective real-world study, alectinib post-brigatinib showed limited overall activity but seems to remain an interesting option for patients with advanced ALK+ NSCLCs who discontinued brigatinib because of toxicity.

    Data Sharing Statement

    The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

    Ethics Approval

    The study conformed to the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines and was approved by the ethics committee Ile de France II Protocol: GFPC 02-2019, date of approval: May 25, 2020. N°20.03.24.67745.

    Informed Consent Statement

    Patients received written and oral information on the study and gave their consent to participate in the study and for the use of their medical data for research purposes.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Funding

    This study received an academic grant from Takeda.

    Disclosure

    Dr Renaud Descourt reports personal fees and non-financial support from AstraZeneca, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Takeda, and Chugai, outside the submitted work. Prof. Dr Florian Guisier reports grants, personal fees from Roche, grants, personal fees from Takeda, grants, personal fees from Pfizer, during the conduct of the study; personal fees from Astra Zeneca, personal fees from BMS, personal fees from Johnson & Johnson, personal fees from MSD, grants, personal fees from Pfizer, grants, personal fees from Roche, personal fees from Sanofi, grants, personal fees from Takeda, personal fees from Viatris, personal fees from Amgen, personal fees from Regeneron, outside the submitted work; Dr Maurice Pérol reports personal fees, non-financial support from Takeda, personal fees, non-financial support from Roche, personal fees, non-financial support from Pfizer, personal fees, non-financial support from AstraZeneca, personal fees, non-financial support from MSD, personal fees from BMS, personal fees, non-financial support from Janssen, personal fees, non-financial support from Amgen, personal fees from Nuvation Bio, personal fees from AnHeart Therapeutics, personal fees from AbbVie, personal fees from Daiichi Sankyo, outside the submitted work; Dr Jacques Cadranel reports personal fees from AZ, personal fees from Takeda, personal fees from Pfizer, personal fees from Roche, personal fees from MSD, personal fees from Daiichi, outside the submitted work; Dr Helene Doubre reports non-financial support, travel expenses from Takeda, non-financial support, travel expenses from Pfizer, non-financial support, travel expenses from MSD, non-financial support, travel expenses from Novartis, non-financial support from Bristol Myers Squibb, non-financial support from Roche, personal fees, non-financial support, travel expenses from leo Pharma, outside the submitted work; Professor Michael Duruisseaux reports non-financial support from Roche, during the conduct of the study; personal fees, non-financial support from Roche, non-financial support from Takeda, personal fees from Pfizer, outside the submitted work; Dr Stéphane Culine reports personal fees from Astellas, personal fees from Bayer, personal fees from Bristol-Myers Squibb, personal fees from Ipsen, personal fees from Johnson and Johnson, personal fees from Merck, personal fees from MSD, outside the submitted work; Dr Bertrand Mennecier reports personal fees from Takeda for lectures, invitation in congress from Takeda. Professor Olivier Bylicki reports personal fees, travel for congress from MSD, personal fees, travel for congress from ASTRA-ZENECA, outside the submitted work; Dr Christos Chouaid reports grants, personal fees, non-financial support from Boehringer Ingelheim, Hoffman-Roche, Takeda, BMS, MSD, Astra Zeneca, Amgen, Janssen and Pfizer, during the conduct of the study; Prof. Dr Laurent Greillier reports grants, personal fees, non-financial support from BMS, grants, personal fees, non-financial support from MSD, grants, personal fees, non-financial support from Takeda, grants, personal fees, non-financial support from Pfizer, grants, personal fees, non-financial support from Roche, grants, personal fees, non-financial support from Amgen, grants, personal fees, non-financial support from Sanofi, grants, personal fees, non-financial support from J&J, grants, personal fees, non-financial support from Lilly, grants, personal fees, non-financial support from Novartis, grants, personal fees, non-financial support from Regeneron, outside the submitted work. The authors report no other conflicts of interest in this work.

    References

    1. Hendriks LE, Kerr KM, Menis J, et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(4):339–357. doi:10.1016/j.annonc.2022.12.009

    2. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK inhibitor-naive advanced ALK-positive NSCLC: final results of phase 3 ALTA-1L trial. J Thorac Oncol. 2021;16(12):2091–2108. doi:10.1016/j.jtho.2021.07.035

    3. Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056–1064. doi:10.1016/j.annonc.2020.04.478

    4. Chazan G, Franchini F, Shah R, et al. Real-world treatment and outcomes in ALK-rearranged NSCLC: results from a large U.S.-based database. JTO Clin Res Rep. 2024;5(8):100662. doi:10.1016/j.jtocrr.2024.100662

    5. Duruisseaux M, Besse B, Cadranel J, et al. Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study. Oncotarget. 2017;8(13):21903–21917. doi:10.18632/oncotarget.15746

    6. Descourt R, Pérol M, Rousseau-Bussac G, et al. Brigatinib for pretreated, ALK-positive, advanced non-small-cell lung cancers: long-term follow-up and focus on post-brigatinib lorlatinib efficacy in the multicenter, real-world BrigALK2 study. Cancers. 2022;14(7):1751. doi:10.3390/cancers14071751

    7. Ahn MJ. Real-world outcomes of 2L ALK TKIs following 1L brigatinib for patients with ALK+ NSCLC from the ALTA-1L Trial. J Thorac Oncol. 2010;5:S200. doi:10.1097/JTO.0b013e3181dd0a8d

    8. Solomon BJ, Bauer TM, Mok TSK, et al. Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study. Lancet Respir Med. 2023;11(4):354–366. doi:10.1016/S2213-2600(22)00437-4

    9. Felip E, Shaw AT, Bearz A, et al. Intracranial and extracranial efficacy of lorlatinib in patients with ALK-positive non-small-cell lung cancer previously treated with second-generation ALK TKIs. Ann Oncol. 2021;32(5):620–630. doi:10.1016/j.annonc.2021.02.012

    10. Baldacci S, Besse B, Avrillon V, et al. Lorlatinib for advanced anaplastic lymphoma kinase-positive non-small cell lung cancer: results of the IFCT-1803 LORLATU cohort. Eur J Cancer. 2022;166:51–59. doi:10.1016/j.ejca.2022.01.018

    11. Solomon BJ, Liu G, Felip E, et al. Lorlatinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer: 5-year outcomes from the phase III CROWN study. J Clin Oncol. 2024;42(29):3400–3409. doi:10.1200/JCO.24.00581

    12. Ou SHI, Nishio M, Ahn MJ, et al. Efficacy of brigatinib in patients with advanced ALK-positive NSCLC who progressed on alectinib or ceritinib: ALK in lung cancer trial of brigAtinib-2 (ALTA-2). J Thorac Oncol. 2022;17(12):1404–1414. doi:10.1016/j.jtho.2022.08.018

    13. Lin JJ, Zhu VW, Schoenfeld AJ, et al. Brigatinib in patients with alectinib-refractory ALK-positive NSCLC. J Thorac Oncol. 2018;13(10):1530–1538. doi:10.1016/j.jtho.2018.06.005

    14. Mudumba R, Nieva JJ, Padula WV. First-line alectinib, brigatinib, and lorlatinib for advanced anaplastic lymphoma kinase-positive non-small cell lung cancer: a cost-effectiveness analysis. Value Health. 2025;28:S1098–3015(25)02284–3. doi:10.1016/j.jval.2025.03.014

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  • Tech Mahindra and Coresight Research Release Report Highlighting Key Global Trends for Building the “Store of the Future”

    Tech Mahindra and Coresight Research Release Report Highlighting Key Global Trends for Building the “Store of the Future”

    Pune, August 12th 2025 – Tech Mahindra (NSE: TECHM), a leading global provider of
    technology consulting and digital solutions to enterprises across industries, in collaboration
    with Coresight Research, a leading research and advisory firm specializing in retail and
    technology, unveiled a global survey report titled “Store of the Future: Unlocking
    Performance Through Innovation.”
    The report provides timely, data-backed insights into
    how retailers are modernizing their in-store operations by focusing on unifying the shopper
    journey, enhancing the shopper experience, optimizing labor productivity, and maximizing
    store sales – the four pillars of building the “Store of the Future.”

    The report defines the store of the future as a technology-enabled, data-integrated retail
    environment designed to elevate customer journey while driving back-end efficiency. Based
    on a survey of 360 retail decision-makers across North America and Europe, the findings
    highlight how leading retailers are turning to technology to solve core operational challenges,
    from ineffective store management to inventory inaccuracies – with 92% actively investing in
    tools to enhance in-store operations.


    Sampath Saagi, Head of Diverse Industry Verticals Group (DIG), Americas, Tech
    Mahindra,

    said,
    “The “Store of the Future” is more than just a connected space, it’s a
    dynamic, data-driven environment where seamless customer experiences meet operational
    efficiency. This report envisions equipping retailers with actionable insights and a practical

    roadmap to navigate their transformation journey – helping them identify where to invest,
    improve store performance, and deliver greater value to customers. Through our
    collaboration with Coresight Research, we aim to empower the industry with data-led
    strategies for building smarter, future-ready stores.”


    Key findings highlight an industry in transition:

    • 92% of retailers are actively investing in technologies to boost in-store operations.

    • 84% of respondents acknowledge persistent operational inefficiencies that affect
      margins and revenue.

    • Enhancing shopper experience emerged as the top priority for 40% of retailers
      building future-ready stores.

    • 57% are investing in advanced data analytics, making it the most widely adopted
      technology, while automated inventory tracking is seen as the most critical need.

    • Retailers anticipate that technology will drive benefits, including improved product
      availability, greater automation, and real-time data insights.

    • Automated inventory tracking is viewed as the most critical capability for future store
      operations.

    • The top three benefits of technology adoption are greater product availability,
      increased automation, and access to real-time data.

    The report outlines that despite widespread optimism towards technologies, challenges
    remain, such as high implementation costs and data security concerns, that continue to slow
    adoption, underscoring the need for a phased, strategic approach to digital transformation.

    Deborah Weinswig, CEO and Founder of Coresight Research, said,

    “Building the “Store
    of the Future” goes beyond deploying isolated technologies; it requires a clear understanding
    of core operational challenges and a cohesive blueprint to solve them. Success hinges on
    aligning investments with both near-term performance goals and long-term scalability to
    create a true competitive edge.”

    The report provides global retailers a roadmap for building scalable, secure, and future-
    ready retail environments – “Store of the Future.”

    For more information about Tech Mahindra’s retail solutions, click here

    About Tech Mahindra

    Coresight Research is a research and advisory firm specializing in retail and technology.
    Established in 2018 by leading global retail analyst Deborah Weinswig, the firm is
    headquartered in New York, with offices in London, Lagos, Hong Kong, Shanghai and
    Mangalore (India). The firm provides data-driven analysis and strategic advisory to clients
    including retailers, brands, real estate owners, enterprise technology companies,
    accelerators and more. For more information, please visit https://coresight.com/

    About Tech Mahindra

    Tech Mahindra (NSE: TECHM) offers technology consulting and digital solutions to global enterprises across industries, enabling transformative scale at unparalleled speed. With Cisco Confidential 150,000+ professionals across 90+ countries helping 1100+ clients, Tech Mahindra provides a
    full spectrum of services including consulting, information technology, enterprise applications,
    business process services, engineering services, network services, customer experience &
    design, AI & analytics, and cloud & infrastructure services. It is the first Indian company in the
    world to have been awarded the Sustainable Markets Initiative’s Terra Carta Seal, which
    recognizes global companies that are actively leading the charge to create a climate and nature-
    positive future. Tech Mahindra is part of the Mahindra Group, founded in 1945, one of the
    largest and most admired multinational federation of companies. For more information on how TechM can partner with you to meet your Scale at Speed™ imperatives, please visit https://www.techmahindra.com

    For more information on Tech Mahindra, please contact:

    [email protected]

    Abhilasha Gupta, Global Head – Corporate Communications & Public Affairs, Tech
    Mahindra

    Email: [email protected] ; [email protected]

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  • Inside the lab-driven quest for the ultimate high

    Inside the lab-driven quest for the ultimate high

    Later stages for some products include one in which the crude extract is purified, with fats, waxes, lipids, and other solids filtered out. Other products cook for 24 to 36 hours in a vacuum oven to purge away residual solvent, the pressure inside the oven lowered so that the solvent evaporates without any of the good stuff boiling off.

    Using solvents isn’t the only way to make an extract. Raw Garden sends a small amount of its harvest to a partner facility, where it’s turned into a hashish-like product called rosin via a simpler process, using only ice water, heat, and pressure. But hydrocarbon extraction is scalable and highly efficient: Raw Garden’s facility processes around 1,200 pounds of cannabis a day, and has plans to expand.

    This isn’t to say there’s no art to it. A concentrate’s consistency—that is, whether the live resin turns into something creamy or crispy or oily—results from the strain one starts with, as well as small, inspired interventions during extraction. What if we whipped the extract before purging it? What if we cured it so that crystals form? Extract bound for vape cartridges sometimes involves an additional step, in which terpenes are evaporated and collected in a distillation column, then selectively reinserted to achieve specific scent and flavor profiles. In Raw Garden’s vape lab, a colorful aroma wheel shows a hundred-plus fragrances one might allegedly encounter in cannabis, like apricot, sage, pine tar, and espresso. “We’re taking aromatic compounds from plants,” says vice president of agricultural operations Casey Birthisel. “There’s a lot here that’s parallel to the perfume industry.”

    Some medical professionals see more alarming parallels, however, to drugs ostensibly harder than cannabis. The sky-high potency of concentrates has raised red flags, as multiple epidemiological studies have found correlations between their frequent use and increased risks of psychosis and cannabis use disorder, a form of dependence. Those risks seem particularly acute for teenagers. Colorado and Washington, the first states to legalize recreational pot, are among the states where bills to limit THC potency have been introduced, then rejected or withdrawn amid industry pushback.

    Meanwhile, according to analyst Adams, sales of marijuana flower made up about 70 percent of the recreational market when the first legal retailers opened in Colorado in 2014. Today, according to point-of-sale data from Adams and market research firm BDSA, that number has dropped to 40 percent. In the same span, sales of vaping and dabbing products have climbed from around 15 percent of the legal market to 32 percent, though the pace of that growth now seems to be slowing.


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  • Physician turnover in China, 2011–2021: a nationwide longitudinal study | Human Resources for Health

    Physician turnover in China, 2011–2021: a nationwide longitudinal study | Human Resources for Health

    Using data from nearly 3.7 million Chinese physicians spanning 11 years, we found that between 2011 and 2021, 19.4% of physicians changed workplace at least once, and the national annual physician turnover rate increased from 1.6 to 4.4%. Geographically, physician turnover in China tended to favor more economically developed regions, such as the eastern region, urban areas, and provincial capital cities. Institutionally, physician turnover between different types of institutions demonstrated reciprocal exchanges with nearly balanced volumes, but there has been a growing appeal for primary care physicians. Younger physicians, those with higher degrees, and those with senior professional titles were more likely to change their workplaces. Non-permanent employment contracts, lower income, heavy workload, and working in rural areas or for a primary care institution were also risk factors for physician turnover.

    Given the limited nationwide research on physician turnover, we identified only one study applied comparable definition of turnover in U.S. reporting national physician turnover rates using Medicare billing data, which increased from 3.7% (2010) to 4.2% (2020). Since 2014, the rate stabilized above 4%, peaking at 4.3% in 2018 [24]. This study reported similar level of national turnover rate but a more significant increase over the past decade. According to a previous survey conducted in 2013 across 11 western Chinese provinces, approximately 29.1% of the 5046 rural health workers indicated intentions to leave [25]. Their results were higher than our finding of 19.4%, which can be attributed to the fact that turnover intentions are generally higher than actual turnover [26]. Furthermore, their study participants came from the western region and rural areas, which were found to have higher turnover risk in this study. Monitoring the long-term dynamics of physician turnover in China is necessary to determine whether the rate will continue to rise or stabilize and whether it will be influenced by relevant policies.

    Our analysis identified increased NTR in primary care institutions. In comparison, a survey of Chinese primary care physicians in 2005 reported that over 8% of health workers left primary care institutions annually, with the majority moving to higher level healthcare facilities [27]. Such improvements were most likely attributable to China’s substantial investments in primary care institutions in underserved areas [17]. Our findings indicated that economically developed regions, such as eastern China and urban areas, demonstrated stronger attractiveness to mobile physicians, which is consistent with research findings from other countries. A 2015 study of Australian general practitioners found a net turnover trend toward major cities [28], while another investigation into Australian primary care physician retention also identified remoteness as a critical factor influencing workforce turnover [29]. Similarly, a nationwide study of all general practices in the UK between 2007 and 2019 revealed that practices in the most deprived areas had higher turnover rates [30]. In terms of the direction of turnover, the overall physician mobility is relatively consistent with the population flow. According to the national population census data released by China, from 2010 to 2021, the proportion of urban population increased by 14.2 percentage points. Guangdong province is the largest province in terms of physician turnover inflow and has also experienced a population increase of 21.7 million over the past decade. The northeast region, as a major turnover-outflow area, has seen a population decrease of 11.0 million.

    Our findings indicate that 14.4% of physician turnover occurred between provinces during the study period, although this proportion is increasing. Similar patterns have been observed in studies from Australia, with just 10% of physician mobility occurring across states [28]. Besides, between 2011 and 2021, while some provinces experienced net turnover losses, the total number of physicians and physician density in all provinces of China increased significantly [16] due to substantial physician inflows during this period. Therefore, current physician turnover is unlikely to have a significant impact on the geographic distribution. However, future studies should quantify such impacts to mitigate potential adverse effects. In addition, given the declining trend in physician inflows, physician turnover may increasingly influence geographic distribution in China in the future.

    This study also discovered several turnover circuits in the Beijing–Tianjin–Hebei urban agglomeration, the Sichuan–Chongqing urban agglomeration, and the Yangtze River Delta region (Shanghai, Jiangsu, Zhejiang, Anhui), which align to China’s regional coordinated development strategies [13]. These areas exhibit geographical proximity but disparities in socioeconomic development levels and medical service capacity. Under the framework of these strategies, standardized professional title evaluation systems and unified social security policies have been implemented across regions, ensuring continuity in benefits for mobile physicians and effectively reducing institutional barriers to talent exchange. Notably, regional collaborations have been significantly enhanced, such as jointly established regional medical centers and delivered telemedicine care, which may encourage the formation of turnover circuits. For instance, elite medical hubs in Beijing and Shanghai that construct regional medical centers usually require physicians to undertake rotational assignments of months in partner regions (e.g., Tianjin, Anhui), exposing them to the professional and living environments of less-developed areas, which has been found to be positive factor to foster the willingness to relocate and practice in underserved regions [31]. Conversely, physicians in less-developed areas gain access to joint training programs and academic exchanges, improving job satisfaction while creating pathways for career advancement to higher tier institutions. However, further research is needed to investigate the turnover patterns within these circuits, as well as the mechanisms for addressing or exacerbating the imbalanced allocation of medical resources.

    This study explored the factors that influence physician turnover in China and found that younger physicians, those with higher levels of education, senior professional titles, lower income, and heavier workloads, as well as those working in rural areas or primary care medical institutions, were more likely to leave their current jobs. Previous studies on the factors influencing physician turnover in individual provinces in China or other countries [30, 32, 33], as well as studies on the factors influencing physician turnover intentions [11, 12, 34], have yielded similar results. Over the past decade, physician turnover in China has been characterized by competition for highly educated and senior professional-level talents in developed regions. Non-permanent employment contracts were found to be an important risk factor for physician turnover in this study, which is consistent with the findings of a study conducted in Hubei, China [35]. Physicians with permanent employment contracts are more likely to feel a greater sense of belonging and are more loyal to their workplace.

    To the best of our knowledge, this is the first study to report turnover among 3.7 million Chinese physicians across the Chinese mainland over an 11-year period. We developed a cohort based on individual-level data, allowing us to not only quantify the level, trajectory, and characteristics of Chinese physician turnover but also to identify individual and institutional factors that influence physician turnover. However, this study has limitations. First, we define turnover rate as the first recorded job change between 2011 and 2021, ignoring job changes that some physicians may have experienced prior to 2011. Nonetheless, our findings suggest that physician turnover prior to 2011 was likely to be low and had little impact on our results. Second, although CHSI requires institutions to update physician information, such as education and professional titles on an annual basis, some institutions may fail to keep up with changes in a timely manner, potentially underestimating the proportion of physicians with higher education levels and senior professional titles in the retention group. However, as more medical institutions use the data collection system for personnel management, and many provinces use it as a qualification check for professional title evaluation, the impact of this issue on our results is being mitigated. Third, the lack of physician turnover causality data prevents differentiation between voluntary (e.g., career transitions) and involuntary turnover (e.g., layoffs), which, however, might require distinct policy interventions. Fourth, the data we used is collected for government management purposes and reported by institutions, with little information on individual physician characteristics, such as marital status and families, which could be potential confounding factors. Fifth, due to limited access to related data, we could not integrate social factors such as population mobility, demographic shifts, and regional healthcare demand patterns into consideration, which would have further enhanced the policy relevance of our findings.

    In summary, China is experiencing a rising turnover rate. Future policies should pay more attention to central, northeastern regions, and rural areas while continue strengthening the primary care physician workforce. Effective intervention may prioritize young professionals and senior experts by ensuring competitive salary packages, and controlling work-related burnout—measures proven effective by multiple studies [36]. Although current mobility patterns may not yet significantly impact overall distribution, continuous monitoring is necessary to guide physician turnover. If physicians continue to concentrate in developed regions, it may increase the fiscal load on healthcare systems and reduce operational efficiency [37]. This study also aims to provide an actionable solution for monitoring nationwide physician mobility by longitudinally linking individual-level administrative data, potentially addressing research gaps in other countries. Finally, updated health workforce data are crucial for understanding the dynamic changes in medical human resources. This will support evidence-based policy advocacy, scientific workforce planning, and effective governance at the regional, national, and global levels.

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  • Musk says he plans to sue Apple for not featuring X or Grok among its top apps

    Musk says he plans to sue Apple for not featuring X or Grok among its top apps

    Billionaire SpaceX, Tesla and X owner Elon Musk says he plans to sue Apple for not featuring X and its Grok artificial intelligence chatbot app in its top recommended apps in its App Store.

    Musk posted the comments on X late Monday, saying, “Hey @Apple App Store, why do you refuse to put either X or Grok in your ‘Must Have’ section when X is the #1 news app in the world and Grok is #5 among all apps? Are you playing politics? What gives? Inquiring minds want to know.”

    Grok is owned by Musk’s artificial intelligence startup xAI.

    Musk went on to say that “Apple is behaving in a manner that makes it impossible for any AI company besides OpenAI to reach #1 in the App Store, which is an unequivocal antitrust violation. xAI will take immediate legal action.”

    He gave no further details.

    There was no immediate comment from Apple, which has faced various allegations of antitrust violations in recent years.

    A federal judge recently found that Apple violated a court injunction in an antitrust case filed by Fortnite maker Epic Games.

    Regulators of the 27-nation European Union fined Apple 500 million euros in April for breaking competition rules by preventing app makers from pointing users to cheaper options outside its App Store.

    Last year, the EU fined the U.S. tech giant nearly $2 billion for unfairly favoring its own music streaming service by forbidding rivals like Spotify from telling users how they could pay for cheaper subscriptions outside of iPhone apps.

    As of early Tuesday, the top app in Apple’s App Store was TikTok, followed by Tinder, Duolingo, YouTube and Bumble. Open AI’s ChatGPT was ranked 7th.

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  • Delivery drones are coming to more US neighborhoods after getting off to a slow start

    Delivery drones are coming to more US neighborhoods after getting off to a slow start

    Delivery drones are so fast they can zip a pint of ice cream to a customer’s driveway before it melts.

    Yet the long-promised technology has been slow to take off in the United States. More than six years after the Federal Aviation Administration approved commercial home deliveries with drones, the service mostly has been confined to a few suburbs and rural areas.

    That could soon change. The FAA proposed a new rule last week that would make it easier for companies to fly drones outside of an operator’s line of sight and therefore over longer distances. A handful of companies do that now, but they had to obtain waivers and certification as an air carrier to deliver packages.

    While the rule is intended to streamline the process, authorized retailers and drone companies that have tested fulfilling orders from the sky say they plan to make drone-based deliveries available to millions more U.S. households.

    Walmart and Wing, a drone company owned by Google parent Alphabet, currently provide deliveries from 18 Walmart stores in the Dallas area. By next summer, they expect to expand to 100 Walmart stores in Atlanta; Charlotte, North Carolina; Houston; and Orlando and Tampa, Florida.

    After launching its Prime Air delivery service in College Station, Texas, in late 2022, Amazon received FAA permission last year to operate autonomous drones that fly beyond a pilot’s line of sight. The e-commerce company has since expand its drone delivery program to suburban Phoenix and has plans to offer the service in Dallas, San Antonio, Texas, and Kansas City.

    The concept of drone delivery has been around for well over a decade. Drone maker Zipline, which works with Walmart in Arkansas and the Dallas-Fort Worth area, began making deliveries to hospitals in Rwanda in 2016. Israel-based Flytrex, one of the drone companies DoorDash works with to carry out orders, launched drone delivery to households in Iceland in 2017.

    But Wing CEO Adam Woodworth said drone delivery has been in “treading water mode” in the U.S. for years, with service providers afraid to scale up because the regulatory framework wasn’t in place.

    “You want to be at the right moment where there’s an overlap between the customer demand, the partner demand, the technical readiness and the regulatory readiness,” Woodworth said. “I think that we’re reaching that planetary alignment right now.”

    DoorDash, which works with both Wing and Flytrex, tested drone drop-offs in rural Virginia and greater Dallas before announcing an expansion into Charlotte. Getting takeout food this way may sound futuristic, but it’s starting to feel normal in suburban Brisbane, Australia, where DoorDash has employed delivery drones for several years, said Harrison Shih, who leads the company’s drone program.

    “It comes so fast and it’s something flying into your neighborhood, but it really does seem like part of everyday life,” Shih said.

    Even though delivery drones are still considered novel, the cargo they carry can be pretty mundane. Walmart said the top items from the more than 150,000 drone deliveries the nation’s largest retailer has completed since 2021 include ice cream, eggs and Reese’s Peanut Butter Cups.

    Unlike traditional delivery, where one driver may have a truck full of packages, drones generally deliver one small order at a time. Wing’s drones can carry packages weighing up to 2.5 pounds. They can travel up to 12 miles round trip. One pilot can oversee up to 32 drones.

    Zipline has a drone that can carry up to 4 pounds and fly 120 miles round trip. Some drones, like Amazon’s, can carry heavier packages.

    Once an order is placed, it’s packaged for flight and attached to a drone at a launch site. The drone automatically finds a route that avoids obstacles. A pilot observes as the aircraft flies to its destinations and lowers its cargo to the ground with retractable cords.

    Shakiba Enayati, an assistant professor of supply chain and analytics at the University of Missouri, St. Louis, researches ways that drones could speed the delivery of critical health supplies like donated organs and blood samples. The unmanned aircraft offer some advantages as a transport method, such as reduced emissions and improved access to goods for rural residents, Enayati said.

    But she also sees plenty of obstacles. Right now, it costs around $13.50 per delivery to carry a package by drone versus $2 for a traditional vehicle, Enayati said. Drones need well-trained employees to oversee them and can have a hard time in certain weather.

    Drones also can have mid-air collisions or tumble from the sky. But people have accepted the risk of road accidents because they know the advantages of driving, Enayati said. She thinks the same thing could happen with drones, especially as improved technology reduces the chance for errors.

    Woodworth added that U.S. airspace is tightly controlled, and companies need to demonstrate to the FAA that their drones are safe and reliable before they are cleared to fly. Even under the proposed new rules, the FAA would set detailed requirements for drone operators.

    “That’s why it takes so long to build a business in the space. But I think it leads to everybody fundamentally building higher quality things,” Woodworth said.

    Others worry that drones may potentially replace human delivery drivers. Shih thinks that’s unlikely. One of DoorDash’s most popular items is 24-packs of water, Shih said, which aren’t realistic for existing drones to ferry.

    “I believe that drone delivery can be fairly ubiquitous and can cover a lot of things. We just don’t think its probable today that it’ll carry a 40-pound bag of dog food to you,” Shih said.

    DoorDash said that in the areas where it offers drone deliveries, orders requiring the services of human delivery drivers also increase.

    That’s been the experience of John Kim, the owner of PurePoke restaurant in Frisco, Texas. Kim signed on to offer drone deliveries through DoorDash last year. He doesn’t know what percentage of his DoorDash customers are choosing the service instead of regular delivery, but his overall DoorDash orders are up 15% this year.

    Kim said he’s heard no complaints from drone delivery customers.

    “It’s very stable, maybe even better than some of the drivers that toss it in the back with all the other orders,” Kim said.

    For some, drones can simply be a nuisance. When the FAA asked for public comments on Amazon’s request to expand deliveries in College Station, numerous residents expressed concern that drones with cameras violated their privacy. Amazon says its drones use cameras and sensors to navigate and avoid obstacles but may record overhead videos of people while completing a delivery.

    Other residents complained about noise.

    “It sounds like a giant nagging mosquito,” one respondent wrote. Amazon has since released a quieter drone.

    But others love the service. Janet Toth of Frisco, Texas, said she saw drone deliveries in Korea years ago and wondered why the U.S. didn’t have them. So she was thrilled when DoorDash began providing drone delivery in her neighborhood.

    Toth now orders drone delivery a few times a month. Her 9-year-old daughter Julep said friends often come over to watch the drone.

    “I love to go outside, wave at the drone, say ‘Thank you’ and get the food,” Julep Toth said.

    ___

    AP Video Journalist Kendria LaFleur contributed from Frisco, Texas.

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