Editorial
Medicines of high health and economic impact: The required balance between innovation and sustainability
Medicamentos de alto impacto sanitario y económico: el necesario equilibrio entre innovación y sostenibilidad
Francisco J. Morales-Olivas
Departamento de Farmacología, Facultad de Medicina y Odontología, Universitat de València, Valencia, Spain
Read
4145
Timeswas read the article
1634
Total PDF
2511
Total HTML
Share statistics
array:23 [ "pii" => "S2341287919300316" "issn" => "23412879" "doi" => "10.1016/j.anpede.2018.12.001" "estado" => "S300" "fechaPublicacion" => "2019-03-01" "aid" => "2585" "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "sco" "cita" => "An Pediatr (Barc). 2019;90:139-40" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 697 "formatos" => array:3 [ "EPUB" => 75 "HTML" => 435 "PDF" => 187 ] ] "Traduccion" => array:1 [ "es" => array:20 [ "pii" => "S1695403319300128" "issn" => "16954033" "doi" => "10.1016/j.anpedi.2018.12.013" "estado" => "S300" "fechaPublicacion" => "2019-03-01" "aid" => "2585" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "sco" "cita" => "An Pediatr (Barc). 2019;90:139-40" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1978 "formatos" => array:3 [ "EPUB" => 128 "HTML" => 1385 "PDF" => 465 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">EDITORIAL</span>" "titulo" => "Medicamentos de alto impacto sanitario y económico: el necesario equilibrio entre innovación y sostenibilidad" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "139" "paginaFinal" => "140" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Medicines of high health and economic impact: The required balance between innovation and sustainability" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Francisco J. Morales-Olivas" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Francisco J." "apellidos" => "Morales-Olivas" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2341287919300316" "doi" => "10.1016/j.anpede.2018.12.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287919300316?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403319300128?idApp=UINPBA00005H" "url" => "/16954033/0000009000000003/v2_202009040640/S1695403319300128/v2_202009040640/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2341287919300079" "issn" => "23412879" "doi" => "10.1016/j.anpede.2018.07.004" "estado" => "S300" "fechaPublicacion" => "2019-03-01" "aid" => "2499" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2019;90:141-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1170 "formatos" => array:3 [ "EPUB" => 97 "HTML" => 805 "PDF" => 268 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Ledipasvir/sofosbuvir combination for chronic hepatitis C infection in children and adolescents" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "141" "paginaFinal" => "147" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Combinación de ledipasvir/sofosbuvir como tratamiento de la infección crónica por hepatitis C" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1052 "Ancho" => 1407 "Tamanyo" => 55451 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Evolution of HCV viral loads. The graph shows the decrease in viral load during treatment with ledipasvir/sofosbuvir. All patients exhibited viral clearance by 6 weeks of treatment.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jesús Quintero, Javier Juampérez, Ecaterina Julio, Vanessa Cabello, Maria Mercadal-Hally, Pere Soler-Palacín, Óscar Segarra, Carlos Rodrigo" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Jesús" "apellidos" => "Quintero" ] 1 => array:2 [ "nombre" => "Javier" "apellidos" => "Juampérez" ] 2 => array:2 [ "nombre" => "Ecaterina" "apellidos" => "Julio" ] 3 => array:2 [ "nombre" => "Vanessa" "apellidos" => "Cabello" ] 4 => array:2 [ "nombre" => "Maria" "apellidos" => "Mercadal-Hally" ] 5 => array:2 [ "nombre" => "Pere" "apellidos" => "Soler-Palacín" ] 6 => array:2 [ "nombre" => "Óscar" "apellidos" => "Segarra" ] 7 => array:2 [ "nombre" => "Carlos" "apellidos" => "Rodrigo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1695403318303175" "doi" => "10.1016/j.anpedi.2018.07.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403318303175?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287919300079?idApp=UINPBA00005H" "url" => "/23412879/0000009000000003/v1_201903020636/S2341287919300079/v1_201903020636/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Medicines of high health and economic impact: The required balance between innovation and sustainability" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "139" "paginaFinal" => "140" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Francisco J. Morales-Olivas" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Francisco J." "apellidos" => "Morales-Olivas" "email" => array:1 [ 0 => "Francisco.Morales@uv.es" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de Farmacología, Facultad de Medicina y Odontología, Universitat de València, Valencia, Spain" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Medicamentos de alto impacto sanitario y económico: el necesario equilibrio entre innovación y sostenibilidad" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The use of medicines in children involves peculiarities due to the lower knowledge of their effects in this population and the methodological and ethical limitations that affect clinical research in paediatrics. In addition, most rare diseases manifest during childhood, and the availability of drugs to treat them ranges from low to non-existent. To these challenges we must add the concern voiced by some authors that medicines with a high economic impact (an euphemism for “very expensive”) threaten the sustainability of the health care system. The picture may appear bleak, but an adequate analysis of the current situation allows us to hope for a future with more and better drugs for paediatric patients.</p><p id="par0010" class="elsevierStylePara elsevierViewall">This issue of <span class="elsevierStyleItalic">Anales de Pediatría</span> includes two articles that contribute to our understanding of the use of new medicines in everyday clinical practice. One<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> describes the real-world effectiveness of ivacaftor, a drug that potentiates the cystic fibrosis transmembrane conductance regulator, which has been found to improve nutritional status and lung function in clinical trials. The study includes 4 children aged 6 to 14 years with cystic fibrosis and the F508del/G551D mutation that were followed up for a median of 24 months of treatment with ivacaftor. The aim was to assess whether the benefits observed in the carefully selected patients in clinical trials would extend to real-world patients that do not meet the inclusion criteria for trials. The article described the outcomes in each individual patient, and all of them improved. None experienced adverse events. The authors discuss the results thoroughly and remark on the usefulness of these studies to assess the effectiveness of drugs that have proven efficacious under experimental conditions. We ought to highlight that one of the patients had to wait to be 6 years of age to receive treatment. The reason was that the drug was not formulated in a way that would allow appropriate dosing in children with weights of less than 25<span class="elsevierStyleHsp" style=""></span>kg and is only approved for use in patients aged 6 years with weights of at least 25<span class="elsevierStyleHsp" style=""></span>kg.</p><p id="par0015" class="elsevierStylePara elsevierViewall">It is remarkable that there are no formulations for young children of a medicine designed to treat a disease that is usually diagnosed in the first years of life, despite the economic advantages that come with its classification as an orphan drug.</p><p id="par0020" class="elsevierStylePara elsevierViewall">It may seem that the publication of the outcomes of 4 patients of heterogeneous characteristics is of little scientific interest, but given the difficulty of conducting clinical trials in this age group, a register of data of treated patients may be very useful to document and analyse the effects of new drugs after authorization to confirm or refute their usefulness in real-world practice. A study that was recently conducted in Ireland<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> by reviewing data from a register of patients with cystic fibrosis and which followed up treatment with ivacaftor over 36 months obtained results similar to those reported by Gómez-Cámara et al, and concluded that ivacaftor not only improved clinical outcomes, but also reduced health care costs in the management of these patients.</p><p id="par0025" class="elsevierStylePara elsevierViewall">This aspect, the reduction of health care costs besides the cost of the drugs themselves, is an important factor to consider in the accurate assessment of the impact of expensive drugs on the sustainability of the health care system. We must not forget that the cost of drugs is not the greatest contributor to health care expenditure, and that at least 30% of the pharmacy bill corresponds to brand-name medicines protected by a patent. Should the sustainability of the system be truly threatened, some experts propose solutions such as fixing drug prices based on the actual value of drugs, capping total expenditure per product, making payments per cured patient, decreasing drug prices based on the number of treated patients or a combination of all of the above so that economic risk would be shared by health care systems and pharmaceutical companies. Price should not be a limitation if a drug truly resolves a problem for which there is no efficacious treatment.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The other such study in the current issue<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> analysed the use of a combination of ledipasvir/sofosbuvir for treatment of children with hepatitis C virus infection. This combination has been authorised since 2014 for patients aged more than 12 years, but according to the authors, it was not at the time they conducted the study, which included 9 patients, 2 of them younger than 10 years, who were treated with half of the habitual dose used in adults (45/200<span class="elsevierStyleHsp" style=""></span>mg versus 90/400<span class="elsevierStyleHsp" style=""></span>mg). To date, there is only one published clinical trial in children, and it only included children aged more than 12 years. The characteristics of the patients were not homogeneous and individual outcomes were not described for each patient, and therefore, although the authors concluded that treatment was effective, with a reduction in viral load at 12 weeks of treatment and only 3 patients experiencing adverse effects that were mild, it would not be possible to enter its effects on children aged less than 12 years to a hypothetical database. The authors noted that in the younger children the combination was given as off-label treatment, but we need to keep in mind that the enactment of Royal Decree RD 1015/2009, which regulates the use of medicines under special conditions, has simplified the off-label use of authorised drugs under conditions other than those stipulated in the summary of product characteristics, for which the previously required official authorization is no longer needed. At present, all that is needed is informing the patient on the associated risks and benefits, documenting it in the health records and obtaining a signed written informed consent. Compassionate use is currently restricted to drugs undergoing clinical trials for their use outside the context of such trials.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Whereas in the past they used to say that children needed to be protected from clinical research, today we can assert that the best way to protect them is to have them partake in ethical and high-quality clinical research, which is not limited to clinical trials. Individual patient data from appropriately documented case series can obviate the need to perform complex trials. This possibility is illustrated by the application of article 45 of the European Paediatric Regulation (1091/2006), which requires pharmaceutical companies to submit all the data available from paediatric studies to update the information on drugs for which research had been conducted and perhaps even published, but is not reflected in the corresponding summary of product characteristics. After 7 years of work, many of these summaries have been modified, including further clarification about paediatric use, specific safety aspects and even new indications.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> The recurrent claim that there is a dearth of paediatric data is not entirely true; instead, there seems to be a considerable amount of scattered data that could be very useful if analysed as a whole. All the data collected through the enactment of article 45 is entered in an open-access database.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The conditions under which drugs are used in the management of paediatric patients have improved in recent years, but off-label use continues to be too frequent. The development of new drugs that are effective, but at a very high price tag, demands that we collect and analyse all the available information to determine as soon as possible whether or not they are of high therapeutic value. Given the difficulties involved in conducting clinical trials in children, the establishment of registers of data published in studies like the ones discussed here could contribute to a better use of medicines.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Morales-Olivas FJ. Medicamentos de alto impacto sanitario y económico: el necesario equilibrio entre innovación y sostenibilidad. An Pediatr (Barc). 2019;90:139–140.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efectividad de ivacaftor en vida real en niños con fibrosis quística y mutación G551D" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D. Gomez-Pastrana" 1 => "C. Nwokoro" 2 => "M. McLean" 3 => "S. Brown" 4 => "N. Christiansen" 5 => "C.S. Pao" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "An Pediatr (Barc)" "fecha" => "2019" "volumen" => "90" "paginaInicial" => "148" "paginaFinal" => "156" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[Electronic publication]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Longitudinal trends in real-world outcomes following initiation of ivacaftor: a cohort study from the cystic fibrosis registry of Ireland" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Kirwan" 1 => "G. Fletcher" 2 => "M. Harrington" 3 => "P. Jeleniewska" 4 => "S. Zhou" 5 => "B. Casserly" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1513/AnnalsATS. 201802-149OC" "Revista" => array:3 [ "tituloSerie" => "Ann Am Thorac Soc" "fecha" => "2018" "itemHostRev" => array:3 [ "pii" => "S1470204512704734" "estado" => "S300" "issn" => "14702045" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combinación de ledipasvir/sofosbuvir como tratamiento de la infección crónica por hepatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Quintero" 1 => "J. Juampérez" 2 => "E. Julio" 3 => "V. Cabello" 4 => "M. Mercadal-Hally" 5 => "P. Soler-Palacín" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.anpedi.2018.07.007" "Revista" => array:2 [ "tituloSerie" => "An Pediatr (Barc)" "fecha" => "2018" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Usage of unpublished paediatric data" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Saint-Raymond" 1 => "B. Pelle" 2 => "C. Zaccaria" 3 => "M. Sennwitz" 4 => "S. Branch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/archdischild-2015-309519" "Revista" => array:6 [ "tituloSerie" => "Arch Dis Child" "fecha" => "2016" "volumen" => "101" "paginaInicial" => "81" "paginaFinal" => "84" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26543071" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "EMA List of recommended changes to product information for nationally-approved medicines. Available from: <a id="intr0010" class="elsevierStyleInterRef" href="http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Paediatric_Regulation/Article_45_and_previous_Worksharing/CMDh-124-2008-Rev4.xls">http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Paediatric_Regulation/Article_45_and_previous_Worksharing/CMDh-124-2008-Rev4.xls</a> [accessed 26.12.18]." ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000009000000003/v1_201903020636/S2341287919300316/v1_201903020636/en/main.assets" "Apartado" => array:4 [ "identificador" => "25501" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Editorial" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000009000000003/v1_201903020636/S2341287919300316/v1_201903020636/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287919300316?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 11 | 16 |
| 2024 October | 48 | 36 | 84 |
| 2024 September | 49 | 28 | 77 |
| 2024 August | 51 | 58 | 109 |
| 2024 July | 40 | 26 | 66 |
| 2024 June | 42 | 21 | 63 |
| 2024 May | 43 | 26 | 69 |
| 2024 April | 38 | 36 | 74 |
| 2024 March | 42 | 16 | 58 |
| 2024 February | 29 | 27 | 56 |
| 2024 January | 29 | 22 | 51 |
| 2023 December | 25 | 19 | 44 |
| 2023 November | 37 | 38 | 75 |
| 2023 October | 32 | 21 | 53 |
| 2023 September | 37 | 21 | 58 |
| 2023 August | 22 | 12 | 34 |
| 2023 July | 25 | 22 | 47 |
| 2023 June | 22 | 30 | 52 |
| 2023 May | 33 | 24 | 57 |
| 2023 April | 24 | 10 | 34 |
| 2023 March | 30 | 19 | 49 |
| 2023 February | 25 | 17 | 42 |
| 2023 January | 22 | 11 | 33 |
| 2022 December | 39 | 16 | 55 |
| 2022 November | 36 | 28 | 64 |
| 2022 October | 34 | 44 | 78 |
| 2022 September | 18 | 30 | 48 |
| 2022 August | 39 | 45 | 84 |
| 2022 July | 32 | 32 | 64 |
| 2022 June | 27 | 46 | 73 |
| 2022 May | 47 | 29 | 76 |
| 2022 April | 30 | 26 | 56 |
| 2022 March | 52 | 43 | 95 |
| 2022 February | 39 | 12 | 51 |
| 2022 January | 56 | 34 | 90 |
| 2021 December | 50 | 38 | 88 |
| 2021 November | 54 | 36 | 90 |
| 2021 October | 66 | 46 | 112 |
| 2021 September | 46 | 37 | 83 |
| 2021 August | 41 | 36 | 77 |
| 2021 July | 30 | 20 | 50 |
| 2021 June | 50 | 26 | 76 |
| 2021 May | 50 | 31 | 81 |
| 2021 April | 156 | 64 | 220 |
| 2021 March | 56 | 36 | 92 |
| 2021 February | 28 | 13 | 41 |
| 2021 January | 39 | 13 | 52 |
| 2020 December | 35 | 13 | 48 |
| 2020 November | 28 | 17 | 45 |
| 2020 October | 27 | 16 | 43 |
| 2020 September | 18 | 13 | 31 |
| 2020 August | 18 | 5 | 23 |
| 2020 July | 15 | 14 | 29 |
| 2020 June | 11 | 7 | 18 |
| 2020 May | 16 | 10 | 26 |
| 2020 April | 21 | 10 | 31 |
| 2020 March | 18 | 6 | 24 |
| 2020 February | 12 | 4 | 16 |
| 2020 January | 16 | 9 | 25 |
| 2019 December | 26 | 10 | 36 |
| 2019 November | 12 | 2 | 14 |
| 2019 October | 16 | 6 | 22 |
| 2019 September | 25 | 6 | 31 |
| 2019 August | 28 | 10 | 38 |
| 2019 July | 24 | 22 | 46 |
| 2019 June | 36 | 14 | 50 |
| 2019 May | 79 | 41 | 120 |
| 2019 April | 55 | 26 | 81 |
| 2019 March | 92 | 34 | 126 |
| 2019 February | 18 | 7 | 25 |
Show all
