Tilauksesta suunnitteluun ohjautuvan tilaus-toimitusketjun analyysi

Tiivistelmä. Tämän tutkimuksen tavoitteena on perehtyä Conlog Oy:n erään projektituotteen tilaustoimitusketjun nykytilaan. Käytännössä kaikki yrityksen tuotteista ovat räätälöitäviä, mutta projektien vaativuusaste riippuu usein tuotteiden sisältämän tekniikan määrästä ja laadusta. Tästä syystä tutkimuksen kohteeksi haluttiin valita asiakkaan lähtökohdista räätälöitävä tuote, joka sisältää verrattain paljon tekniikkaa. Voidaankin puhua tilauksesta suunnitteluun ohjautuvasta tuotantostrategiasta. Tämä asettaa etenkin yrityksen projektinjohdon, suunnittelun, hankinnan ja niiden prosessien vaatimustason korkealle. Nykytilan analyysin perusteella pyritään tuomaan esille toimitusketjun kannalta oleellisia, mahdollisen jatkokehittämisen arvoisia kohtia. Koska tilaus-toimitusketjut liittyvät mitä suurimmilta osin prosesseihin, syvennytään prosesseihin ensin kirjallisuuskatsauksessa ja myöhemmin varsinaisessa nykytilan kuvaamisessa. Tilaustoimitusketjuilla voidaan yleisesti ottaen katsoa olevan sekä yrityksen sisäinen, että ulkoinen ulottuvuus. Tutkimuksessa suoritetaankin katsaus yrityksen sisäisiin tilaustoimitusketjun prosesseihin, josta siirrytään tarkastelemaan ketjua laajemmasta perspektiivistä. Tämä työ on tapaustutkimus, jossa pääasiallisena tiedonkeruumenetelmänä on hyödynnetty yrityksen avainhenkilöiden haastatteluita laadullisen tutkimuksen menetelmin. Muita tietolähteitä ovat olleet esimerkiksi yrityksen tietojärjestelmät ja arkistot sekä työntekijöiden henkilökohtaiset kirjanpidot ja sähköpostikeskustelut. Tutkimuksen peruslähtökohtana tunnistettiin yrityksen tuotantostrategia (tilauksesta suunnitteluun, engineer-to-order) sekä tilaus-toimitusprosessi aliprosesseineen. Yrityksen aiemmissa prosessikuvauksissa ei tilaus-toimitusprosessia ole tunnistettu sellaisenaan. Prosesseista pyrittiin luomaan todenmukaiset kuvaukset, jotta prosesseissa mahdollisesti ilmenevä tarpeeton monimutkaisuus saataisiin tuotua esille jatkokehittämisen pohjaksi. Tutkittavan tilaus-toimitusketjun suurimmat haasteet vaikuttavat liittyvän informaation virtaukseen ketjun osapuolten ja prosessien välillä ja ketjun toiminnan kehittämiseen liittyviä ehdotuksia esitetään työn lopussa. Vaikka ehdotukset perustuvat nyt tutkittavan toimitusketjun haasteisiin, ovat ne luonteeltaan sellaisia, että niitä on mahdollista toteuttaa laaja-alaisesti kohdeyrityksessä.Analysis of an engineer-to-order supply chain. Abstract. The purpose of this thesis is to examine the current state of the order-supply chain of the selected project for the target company. Virtually all the company’s products are customizable, but the degree of customization and therefore complexity of projects often depends on the amount and quality of the technology they contain. For this reason, the aim was to select a customer customized product that contains a relatively large amount of technology. Thus, the products can be said to be engineered-to-order. This sets high requirements for the company’s project management, design, sourcing and the processes of those. The analysis of the current situation seeks to highlight relevant points in the supply chain that deserve further development. As supply chains are largely process-related, the study will first delve into the processes in the literature review and later in the actual current state description. Supply chains can generally be considered to have both an internal and an external dimension. The starting point of the study was to look at the company’s internal supply chain processes, from which it is natural to move into a wider perspective of the chain. This thesis is a case study where qualitative methods have been utilized. Interviews with key personnel have been the primary method of data collection while other sources of information have included company information systems and archives, as well as employee personal records and email conversations. The basic premise of this study was to identify the company’s production strategy (engineer-to-order) and the order-delivery process with its sub-processes. In the company’s previous process descriptions, the order-delivery process had not been identified as such. Process mapping and descriptions were aimed to be created to be as realistic as possible in order to highlight any unnecessary complexity of the processes as a basis for further development. According to the results of the study, the major challenges in the order-supply chain are related to the flow of information between the parties and processes in the chain and the related development proposals are presented at the end of the thesis. Although the proposals are based on the challenges of the selected supply chain, they are capable of being implemented on a wider perspective in the target company as well

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial

BACKGROUND: As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. METHODS: We did a randomised, open-label, phase 3 trial at 133 hospitals and research centres in 21 countries. We enrolled patients (aged 6518 years) with a diagnosis of multiple myeloma and measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2, who received one to three previous regimens, including a lenalidomide-containing regimen for at least two consecutive cycles. We randomly assigned patients (1:1) to bortezomib and dexamethasone with or without pomalidomide using a permutated blocked design in blocks of four, stratified according to age, number of previous regimens, and concentration of \u3b2(2) microglobulin at screening. Bortezomib (1\ub73 mg/m(2)) was administered intravenously until protocol amendment 1 then either intravenously or subcutaneously on days 1, 4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg [10 mg if age >75 years]) was administered orally on the same days as bortezomib and the day after. Patients allocated pomalidomide received 4 mg orally on days 1-14. Treatment cycles were every 21 days. The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by an independent review committee. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered at ClinicalTrials.gov, number NCT01734928; patients are no longer being enrolled. FINDINGS: Between Jan 7, 2013, and May 15, 2017, 559 patients were enrolled. 281 patients were assigned pomalidomide, bortezomib, and dexamethasone and 278 were allocated bortezomib and dexamethasone. Median follow-up was 15\ub79 months (IQR 9\ub79-21\ub77). Pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared with bortezomib and dexamethasone (median 11\ub720 months [95% CI 9\ub766-13\ub773] vs 7\ub710 months [5\ub788-8\ub748]; hazard ratio 0\ub761, 95% CI 0\ub749-0\ub777; p<0\ub70001). 278 patients received at least one dose of pomalidomide, bortezomib, and dexamethasone and 270 patients received at least one dose of bortezomib and dexamethasone, and these patients were included in safety assessments. The most common grade 3 or 4 treatment-emergent adverse events were neutropenia (116 [42%] of 278 patients vs 23 [9%] of 270 patients; nine [3%] vs no patients had febrile neutropenia), infections (86 [31%] vs 48 [18%]), and thrombocytopenia (76 [27%] vs 79 [29%]). Serious adverse events were reported in 159 (57%) of 278 patients versus 114 (42%) of 270 patients. Eight deaths were related to treatment; six (2%) were recorded in patients who received pomalidomide, bortezomib, and dexamethasone (pneumonia [n=2], unknown cause [n=2], cardiac arrest [n=1], cardiorespiratory arrest [n=1]) and two (1%) were reported in patients who received bortezomib and dexamethasone (pneumonia [n=1], hepatic encephalopathy [n=1]). INTERPRETATION: Patients with relapsed or refractory multiple myeloma who previously received lenalidomide had significantly improved progression-free survival when treated with pomalidomide, bortezomib, and dexamethasone compared with bortezomib and dexamethasone. Adverse events accorded with the individual profiles of pomalidomide, bortezomib, and dexamethasone. This study supports use of pomalidomide, bortezomib, and dexamethasone as a treatment option in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. FUNDING: Celgene

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial

Background As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide.Methods We did a randomised, open-label, phase 3 trial at 133 hospitals and research centres in 21 countries. We enrolled patients (aged >= 18 years) with a diagnosis of multiple myeloma and measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2, who received one to three previous regimens, including a lenalidomide-containing regimen for at least two consecutive cycles. We randomly assigned patients (1:1) to bortezomib and dexamethasone with or without pomalidomide using a permutated blocked design in blocks of four, stratified according to age, number of previous regimens, and concentration of beta(2) microglobulin at screening. Bortezomib (1.3 mg/m(2)) was administered intravenously until protocol amendment 1 then either intravenously or subcutaneously on days 1,4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg [10 mg if age >75 years]) was administered orally on the same days as bortezomib and the day after. Patients allocated pomalidomide received 4 mg orally on days 1-14. Treatment cycles were every 21 days. The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by an independent review committee. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered at ClinicalTrials.gov, number NCT01734928; patients are no longer being enrolled.Findings Between Jan 7, 2013, and May 15,2017,559 patients were enrolled. 281 patients were assigned pomalidomide, bortezomib, and dexamethasone and 278 were allocated bortezomib and dexamethasone. Median follow-up was 15.9 months (IQR 9.9-21.7). Pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared with bortezomib and dexamethasone (median 11.20 months [95% CI 9.66-13-73] vs 7.10 months [5.88-8-48]; hazard ratio 0.61, 95% CI 0.49-0-77; p<0-0001). 278 patients received at least one dose of pomalidomide, bortezomib, and dexamethasone and 270 patients received at least one dose of bortezomib and dexamethasone, and these patients were included in safety assessments. The most common grade 3 or 4 treatment-emergent adverse events were neutropenia (116 [42%] of 278 patients vs 23 [9%1 of 270 patients; nine p.m vs no patients had febrile neutropenia), infections (86 [31%] vs 48 118%1), and thrombocytopenia (76 [27%1 vs 79 [29%]). Serious adverse events were reported in 159 (57%) of 278 patients versus 114 (42%) of 270 patients. Eight deaths were related to treatment; six (2%) were recorded in patients who received pomalidomide, bortezomib, and dexamethasone (pneumonia [n=2], unknown cause [n=2], cardiac arrest [n=1], cardiorespiratory arrest [n=11) and two (1%) were reported in patients who received bortezomib and dexamethasone (pneumonia In=11, hepatic encephalopathy [n=1.]).Interpretation Patients with relapsed or refractory multiple myeloma who previously received lenalidomide had significantly improved progression-free survival when treated with pomalidomide, bortezomib, and dexamethasone compared with bortezomib and dexamethasone. Adverse events accorded with the individual profiles of pomalidomide, bortezomib, and dexamethasone. This study supports use of pomalidomide, bortezomib, and dexamethasone as a treatment option in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. Copyright (C) 2019 Elsevier Ltd. All rights reserved