Petra Brhlikova | Newcastle University (original) (raw)
Papers by Petra Brhlikova
Abstract: Oxytocin is a natural hormone with uterine stimulant properties that plays a prominent ... more Abstract: Oxytocin is a natural hormone with uterine stimulant properties that plays a prominent role in obstetric practice. Clinical guidelines for oxytocin use intrapartum emphasise that injudicious use has serious potential for adverse outcomes for mother and baby. Oxytocin is readily available in South Asia and widely used in ways that flout these guidelines. Yet recommendations for active management of third stage of labour (AMTSL) include the administration of oxytocin to prevent post-partum haemorrhage (PPH). Troublingly, these proposals seem to ignore oxytocin’s already extensive life independent of policy interventions. Taking oxytocin as an example, the paper argues that policy-makers urgently need to engage with the everyday realities of drug availability and use in South Asia. I
Journal of Pharmaceutical Policy and Practice, Nov 9, 2023
Background In India, states have licensed the manufacture of large numbers of fixed-dose combinat... more Background In India, states have licensed the manufacture of large numbers of fixed-dose combination (FDC) drugs without the required prior approval of the central regulator. This paper describes two major regulatory initiatives to address the problem, which began in 2007 and 2013, and examines whether they have been sufficient to remove centrally unapproved systemic antibiotic FDCs from the market. Methods Information was extracted from documents published by the central regulator and the ministry of health, including the National List of Essential Medicines (NLEM), and court judgments, and analysed alongside sales volume data for 2008-2020 using PharmaTrac market dataset. The regulatory initiatives permitted 68 formulations to be given de facto approvals ('No Objection Certificates') outside the statutory regime, banned 46 FDCs and restricted one FDC. Market data show that FDCs as a proportion of total antibiotic sales increased from 32.9 in 2008 to 37.3% in 2020. The total number of antibiotic FDC formulations on the market fell from 574 (2008) to 395 (2020). Formulations with a record of prior central approval increased from 86 (2008) to 94 (2020) and their share of the antibiotic FDC sales increased from 32.0 to 55.3%. In 2020, an additional 23 formulations had been permitted de facto approval, accounting for 10.6% of the antibiotic FDC sales. Even in 2020, most marketed formulations (70.4%, 278/395) were unapproved or banned, and comprised a 15.9% share of the antibiotic FDC sales. The share of NLEM-listed antibiotic FDC sales increased from 21.2 (2008) to 26.7% (2020). The initiatives had limited impact. Regulatory enforcement has been slow and weak, with many unapproved, and even banned, FDCs remaining on the market.
Journal of the Royal Society of Medicine
Objectives To audit national drug registers (NDRs) in Kenya, United Republic of Tanzania and Ugan... more Objectives To audit national drug registers (NDRs) in Kenya, United Republic of Tanzania and Uganda with respect to national Essential Medicine Lists (EMLs) and to conduct an analysis of highly registered products including a sub-analysis of highly registered antimicrobial products. Design Retrospective analysis of registration of essential medicines and medicinal products on NDRs as of February 2018. Setting Not applicable. Participants None. Main outcome measures Registration status of essential medicines by country, essential medicine status of registered products by country and medicines with more than 50 registrations across all three countries. Results A high proportion of essential medicines are not registered: Kenya 28% (175/632), United Republic of Tanzania 50% (400/797) and Uganda 40% (266/663). Of registered products on the NDRs, more than half are not essential: Kenya 71% (4350/6151), United Republic of Tanzania 64% (2278/3590) and Uganda 58% (2268/3896). When the three ...
Journal of Pharmaceutical Policy and Practice
Background Essential medicines (EMs) are those that satisfy the basic healthcare needs of the pop... more Background Essential medicines (EMs) are those that satisfy the basic healthcare needs of the population. However, access to EMs remains a global health challenge. The World Health Organization (WHO) and the East African Community (EAC) manufacturing plan 2017–2027 support local production of EMs as a strategy to improve access to medicines. The aim of this study was to determine for each therapeutic class on the national essential medicine lists (NEMLs) of Kenya, Tanzania and Uganda, the number of EMs produced in each country. Methods In 2018, we analysed NEMLs and national drug registers (NDRs) in each country to identify local manufacturers and local products by EM status. For each local manufacturer we determined the number of EM products and individual EMs, and analysed EMs in each therapeutic class by registration status and whether produced locally. Results There were nine companies manufacturing locally in Kenya, four in Tanzania and six in Uganda. Most local medicine produc...
Bulletin of the World Health Organization
Objective To analyse sales of fixed-dose combination and single antibiotics in India in relation ... more Objective To analyse sales of fixed-dose combination and single antibiotics in India in relation to World Health Organization (WHO) recommendations and national regulatory efforts to control antibiotic sales. Methods We extracted data on sales volumes of systemic antibiotics in India from a market research company sales database. We compared the market share of antibiotic sales in 2020 by WHO AWaRe (Access, Watch and Reserve) category and for those under additional national regulatory controls. We also analysed sales of fixed-dose combinations that were: formally approved for marketing or had a no-objection certificate; on the national essential medicines list; and on the WHO list of not-recommended antibiotics. Findings There were 78 single and 112 fixed-dose combination antibiotics marketed in India, accounting for 7.6 and 4.5 billion standard units of total sales, respectively. Access, Watch and Reserve antibiotics comprised 5.8, 5.6 and 0.1 billion standard units of total market sales, respectively. All additionally controlled antibiotics were Watch and Reserve antibiotics (23.6%; 2.9 billion standard units of total sales). Fixed-dose combinations on the WHO not-recommended list were marketed in 229 formulations, with 114 formulations (49.8%) having no record of formal approval or no-objection certificate. While there were no not-recommended fixed-dose combinations on the national list of essential medicines, 13 of the top-20 selling antibiotic fixed-dose combinations were WHO not-recommended. Conclusion The sale of Watch group drugs, and antibiotics banned or not approved, needs active investigation and enforcement in India. The evidence base underpinning formal approvals and no-objection certificates for not-recommended fixed-dose combinations should be audited. Research Systemic antibiotic sales, India Aashna Mehta et al.
2 Introduction compete and w hen two for-profit firms compete. Among other results, the model rev... more 2 Introduction compete and w hen two for-profit firms compete. Among other results, the model reveals that the nonprofit firm is a natural leader in the market. The for-profit firm prefers a nonprofit competitor to a for-profit one. Moreover, the for-profit firm is better o ff w hen its nonprofit competitor is e ffi cient and subsidi z ed.
Journal of Pharmaceutical Policy and Practice
Additional file 3. Interview guide regulators.
Health and Social Justice (New Delhi) provided resources drawn upon in writing this paper. Neithe... more Health and Social Justice (New Delhi) provided resources drawn upon in writing this paper. Neither ESRC nor DFID is responsible for views advanced here.
Additional file 6. Interview guide regulators follow up.
Additional file 5. Interview guide donors/NGOs.
Additional file 2. Key informants.
Additional file 4. Interview guide procurers/distributors.
Additional file 1. Resolution of differences between the Ugandan EML and NDR.
Analysis of three trials of cognitive behaviour therapy found that activity levels before and aft... more Analysis of three trials of cognitive behaviour therapy found that activity levels before and after therapy were similar, despite improvements being reported on fatigue and other subjective measures. 3 This fi nding suggests that patients might simply substitute the activity component of cognitive behaviour therapy for other activities; 4
Globalization and Health, 2015
Background: Local pharmaceutical production has been endorsed by the WHO as a means of addressing... more Background: Local pharmaceutical production has been endorsed by the WHO as a means of addressing health priorities of developing countries. However, local producers of essential medicines must comply with international pharmaceutical standards in order to be eligible to compete in donor tenders. These standards determine production rights for on-patent and off-patent medicines, and guide international procurement of medicines. We reviewed the literature on the impact of Good Manufacturing Practice (GMP) on local production; a gap analysis from the literature review indicated a need for further research. Over sixty interviews were conducted with people involved in the Nepali pharmaceutical production and distribution chain from 2006 to 2009 on the GMP areas of relevance: regulatory capacity, staffing, funding and training, resourcing of GMP, inspectors' interpretation of the rules and compliance. Results: Although Nepal producers have increased their overall share of the domestic market, only the public manufacturer, Royal Drugs, focuses on medicines for public health programmes; private producers engage mainly in brand competition for private markets, not essential medicines. Nepali regulators and producers state that implementation of GMP standards is hindered by low regulatory capacity, insufficient training of staff in the industry, financial constraints and lack of investment for upgrading capital. The transition period to mandatory compliance with WHO GMP rules is lengthy. Less than half of private producers had WHO GMP in 2013. Producers are not directly affected by international harmonisation of standards as they do not export medicines and the Nepali regulator does not enforce the WHO standards strictly. Without an international GMP certificate they cannot tender for donor dependent health programmes. Conclusions: In Nepal, local private manufacturers focus mainly on brand competition for private consumption not essential medicines, the government preferentially procures essential medicines from the only public producer while donor funded programmes rely on international manufacturers compliant with international GMP standards. We also found evidence of private hospitals bypassing national medicines approvals process. Policies in support of local pharmaceutical production in developing countries as a source of essential medicines need to examine carefully how GMP regulations impact on regulators, local industry and production of essential medicines in practice.
Bulletin of the World Health Organization
Abstract Objective To determine the proportion of essential and non-essential antimicrobial medic... more Abstract Objective To determine the proportion of essential and non-essential antimicrobial medicines that are registered on the drug registers in Kenya, Uganda and United Republic of Tanzania. Methods We categorized all antimicrobials on the national drug registers and essential medicines lists of the three countries using the British National Formulary. We also categorized all antibiotics according to the World Health Organization access, watch and reserve (AWaRe) classification. We calculated the proportions of essential and non-essential antimicrobials that were registered by antimicrobial class and AWaRe classification. Findings In 2018, Kenya had 2105 registered antimicrobials, Uganda had 1563 and the United Republic of Tanzania had 1327. Of these medicines, 1353 (64.3%) were non-essential in Kenya, 798 (51.1%) in Uganda and 706 (53.2%) in the United Republic of Tanzania. Kenya had 160 antimicrobials on its national essential medicines lists, Uganda had 187 and the United Republic of Tanzania had 182; of these, 33 (20.7%), 50 (26.7%) and 52 (28.6%) were not registered, respectively. High proportions of antimycobacterial and antiparasitic medicines were not registered. Of essential access antibiotics, 14.3% (4/28) were not registered in Kenya, 8.6% (3/35) in Uganda and 20.5% (8/39) in the United Republic of Tanzania, nor were 25.0% (3/12) of watch antibiotics in Kenya, 14.3% (2/14) in Uganda and 19.1% (4/21) in the United Republic of Tanzania. Conclusion Suboptimal registration of essential antimicrobials and over-registration of non-essential antimicrobials may encourage inappropriate use, especially since non-essential antimicrobials do not appear on national treatment guidelines. Countries should prioritize registration of the antimicrobial medicines on their essential medicines lists.
Supplemental material, JRS899308 Supplemental material for Will HPV vaccination prevent cervical ... more Supplemental material, JRS899308 Supplemental material for Will HPV vaccination prevent cervical cancer? by Claire P Rees, Petra Brhlikova and Allyson M Pollock in Journal of the Royal Society of Medicine
Background: Building appropriate levels of trust in pharmaceuticals is a painstaking and challeng... more Background: Building appropriate levels of trust in pharmaceuticals is a painstaking and challenging task, involving participants from different spheres of life, including producers, distributors, retailers, prescribers, patients and the mass media. Increasingly, however, trust is not just a national matter, but involves cross-border flows of knowledge, threats and promises. Methods: Data for this paper comes from the project ‘Tracing Pharmaceuticals in South Asia’, which used ethnographic fieldwork and qualitative interviews to compared the trajectories of three pharmaceuticals (Rifampicin, Oxytocin and Fluoxetine) from producer to patient in three sites (north India, West Bengal and Nepal) between 2005-08. Results: We argue that issues of trust are crucial in reducing the likelihood of appropriate use of medicines. Unlike earlier discussions of trust, we suggest that trust contexts beyond the patient-practitioner relationship are important. We illustrate these arguments through th...
Abstract: Oxytocin is a natural hormone with uterine stimulant properties that plays a prominent ... more Abstract: Oxytocin is a natural hormone with uterine stimulant properties that plays a prominent role in obstetric practice. Clinical guidelines for oxytocin use intrapartum emphasise that injudicious use has serious potential for adverse outcomes for mother and baby. Oxytocin is readily available in South Asia and widely used in ways that flout these guidelines. Yet recommendations for active management of third stage of labour (AMTSL) include the administration of oxytocin to prevent post-partum haemorrhage (PPH). Troublingly, these proposals seem to ignore oxytocin’s already extensive life independent of policy interventions. Taking oxytocin as an example, the paper argues that policy-makers urgently need to engage with the everyday realities of drug availability and use in South Asia. I
Journal of Pharmaceutical Policy and Practice, Nov 9, 2023
Background In India, states have licensed the manufacture of large numbers of fixed-dose combinat... more Background In India, states have licensed the manufacture of large numbers of fixed-dose combination (FDC) drugs without the required prior approval of the central regulator. This paper describes two major regulatory initiatives to address the problem, which began in 2007 and 2013, and examines whether they have been sufficient to remove centrally unapproved systemic antibiotic FDCs from the market. Methods Information was extracted from documents published by the central regulator and the ministry of health, including the National List of Essential Medicines (NLEM), and court judgments, and analysed alongside sales volume data for 2008-2020 using PharmaTrac market dataset. The regulatory initiatives permitted 68 formulations to be given de facto approvals ('No Objection Certificates') outside the statutory regime, banned 46 FDCs and restricted one FDC. Market data show that FDCs as a proportion of total antibiotic sales increased from 32.9 in 2008 to 37.3% in 2020. The total number of antibiotic FDC formulations on the market fell from 574 (2008) to 395 (2020). Formulations with a record of prior central approval increased from 86 (2008) to 94 (2020) and their share of the antibiotic FDC sales increased from 32.0 to 55.3%. In 2020, an additional 23 formulations had been permitted de facto approval, accounting for 10.6% of the antibiotic FDC sales. Even in 2020, most marketed formulations (70.4%, 278/395) were unapproved or banned, and comprised a 15.9% share of the antibiotic FDC sales. The share of NLEM-listed antibiotic FDC sales increased from 21.2 (2008) to 26.7% (2020). The initiatives had limited impact. Regulatory enforcement has been slow and weak, with many unapproved, and even banned, FDCs remaining on the market.
Journal of the Royal Society of Medicine
Objectives To audit national drug registers (NDRs) in Kenya, United Republic of Tanzania and Ugan... more Objectives To audit national drug registers (NDRs) in Kenya, United Republic of Tanzania and Uganda with respect to national Essential Medicine Lists (EMLs) and to conduct an analysis of highly registered products including a sub-analysis of highly registered antimicrobial products. Design Retrospective analysis of registration of essential medicines and medicinal products on NDRs as of February 2018. Setting Not applicable. Participants None. Main outcome measures Registration status of essential medicines by country, essential medicine status of registered products by country and medicines with more than 50 registrations across all three countries. Results A high proportion of essential medicines are not registered: Kenya 28% (175/632), United Republic of Tanzania 50% (400/797) and Uganda 40% (266/663). Of registered products on the NDRs, more than half are not essential: Kenya 71% (4350/6151), United Republic of Tanzania 64% (2278/3590) and Uganda 58% (2268/3896). When the three ...
Journal of Pharmaceutical Policy and Practice
Background Essential medicines (EMs) are those that satisfy the basic healthcare needs of the pop... more Background Essential medicines (EMs) are those that satisfy the basic healthcare needs of the population. However, access to EMs remains a global health challenge. The World Health Organization (WHO) and the East African Community (EAC) manufacturing plan 2017–2027 support local production of EMs as a strategy to improve access to medicines. The aim of this study was to determine for each therapeutic class on the national essential medicine lists (NEMLs) of Kenya, Tanzania and Uganda, the number of EMs produced in each country. Methods In 2018, we analysed NEMLs and national drug registers (NDRs) in each country to identify local manufacturers and local products by EM status. For each local manufacturer we determined the number of EM products and individual EMs, and analysed EMs in each therapeutic class by registration status and whether produced locally. Results There were nine companies manufacturing locally in Kenya, four in Tanzania and six in Uganda. Most local medicine produc...
Bulletin of the World Health Organization
Objective To analyse sales of fixed-dose combination and single antibiotics in India in relation ... more Objective To analyse sales of fixed-dose combination and single antibiotics in India in relation to World Health Organization (WHO) recommendations and national regulatory efforts to control antibiotic sales. Methods We extracted data on sales volumes of systemic antibiotics in India from a market research company sales database. We compared the market share of antibiotic sales in 2020 by WHO AWaRe (Access, Watch and Reserve) category and for those under additional national regulatory controls. We also analysed sales of fixed-dose combinations that were: formally approved for marketing or had a no-objection certificate; on the national essential medicines list; and on the WHO list of not-recommended antibiotics. Findings There were 78 single and 112 fixed-dose combination antibiotics marketed in India, accounting for 7.6 and 4.5 billion standard units of total sales, respectively. Access, Watch and Reserve antibiotics comprised 5.8, 5.6 and 0.1 billion standard units of total market sales, respectively. All additionally controlled antibiotics were Watch and Reserve antibiotics (23.6%; 2.9 billion standard units of total sales). Fixed-dose combinations on the WHO not-recommended list were marketed in 229 formulations, with 114 formulations (49.8%) having no record of formal approval or no-objection certificate. While there were no not-recommended fixed-dose combinations on the national list of essential medicines, 13 of the top-20 selling antibiotic fixed-dose combinations were WHO not-recommended. Conclusion The sale of Watch group drugs, and antibiotics banned or not approved, needs active investigation and enforcement in India. The evidence base underpinning formal approvals and no-objection certificates for not-recommended fixed-dose combinations should be audited. Research Systemic antibiotic sales, India Aashna Mehta et al.
2 Introduction compete and w hen two for-profit firms compete. Among other results, the model rev... more 2 Introduction compete and w hen two for-profit firms compete. Among other results, the model reveals that the nonprofit firm is a natural leader in the market. The for-profit firm prefers a nonprofit competitor to a for-profit one. Moreover, the for-profit firm is better o ff w hen its nonprofit competitor is e ffi cient and subsidi z ed.
Journal of Pharmaceutical Policy and Practice
Additional file 3. Interview guide regulators.
Health and Social Justice (New Delhi) provided resources drawn upon in writing this paper. Neithe... more Health and Social Justice (New Delhi) provided resources drawn upon in writing this paper. Neither ESRC nor DFID is responsible for views advanced here.
Additional file 6. Interview guide regulators follow up.
Additional file 5. Interview guide donors/NGOs.
Additional file 2. Key informants.
Additional file 4. Interview guide procurers/distributors.
Additional file 1. Resolution of differences between the Ugandan EML and NDR.
Analysis of three trials of cognitive behaviour therapy found that activity levels before and aft... more Analysis of three trials of cognitive behaviour therapy found that activity levels before and after therapy were similar, despite improvements being reported on fatigue and other subjective measures. 3 This fi nding suggests that patients might simply substitute the activity component of cognitive behaviour therapy for other activities; 4
Globalization and Health, 2015
Background: Local pharmaceutical production has been endorsed by the WHO as a means of addressing... more Background: Local pharmaceutical production has been endorsed by the WHO as a means of addressing health priorities of developing countries. However, local producers of essential medicines must comply with international pharmaceutical standards in order to be eligible to compete in donor tenders. These standards determine production rights for on-patent and off-patent medicines, and guide international procurement of medicines. We reviewed the literature on the impact of Good Manufacturing Practice (GMP) on local production; a gap analysis from the literature review indicated a need for further research. Over sixty interviews were conducted with people involved in the Nepali pharmaceutical production and distribution chain from 2006 to 2009 on the GMP areas of relevance: regulatory capacity, staffing, funding and training, resourcing of GMP, inspectors' interpretation of the rules and compliance. Results: Although Nepal producers have increased their overall share of the domestic market, only the public manufacturer, Royal Drugs, focuses on medicines for public health programmes; private producers engage mainly in brand competition for private markets, not essential medicines. Nepali regulators and producers state that implementation of GMP standards is hindered by low regulatory capacity, insufficient training of staff in the industry, financial constraints and lack of investment for upgrading capital. The transition period to mandatory compliance with WHO GMP rules is lengthy. Less than half of private producers had WHO GMP in 2013. Producers are not directly affected by international harmonisation of standards as they do not export medicines and the Nepali regulator does not enforce the WHO standards strictly. Without an international GMP certificate they cannot tender for donor dependent health programmes. Conclusions: In Nepal, local private manufacturers focus mainly on brand competition for private consumption not essential medicines, the government preferentially procures essential medicines from the only public producer while donor funded programmes rely on international manufacturers compliant with international GMP standards. We also found evidence of private hospitals bypassing national medicines approvals process. Policies in support of local pharmaceutical production in developing countries as a source of essential medicines need to examine carefully how GMP regulations impact on regulators, local industry and production of essential medicines in practice.
Bulletin of the World Health Organization
Abstract Objective To determine the proportion of essential and non-essential antimicrobial medic... more Abstract Objective To determine the proportion of essential and non-essential antimicrobial medicines that are registered on the drug registers in Kenya, Uganda and United Republic of Tanzania. Methods We categorized all antimicrobials on the national drug registers and essential medicines lists of the three countries using the British National Formulary. We also categorized all antibiotics according to the World Health Organization access, watch and reserve (AWaRe) classification. We calculated the proportions of essential and non-essential antimicrobials that were registered by antimicrobial class and AWaRe classification. Findings In 2018, Kenya had 2105 registered antimicrobials, Uganda had 1563 and the United Republic of Tanzania had 1327. Of these medicines, 1353 (64.3%) were non-essential in Kenya, 798 (51.1%) in Uganda and 706 (53.2%) in the United Republic of Tanzania. Kenya had 160 antimicrobials on its national essential medicines lists, Uganda had 187 and the United Republic of Tanzania had 182; of these, 33 (20.7%), 50 (26.7%) and 52 (28.6%) were not registered, respectively. High proportions of antimycobacterial and antiparasitic medicines were not registered. Of essential access antibiotics, 14.3% (4/28) were not registered in Kenya, 8.6% (3/35) in Uganda and 20.5% (8/39) in the United Republic of Tanzania, nor were 25.0% (3/12) of watch antibiotics in Kenya, 14.3% (2/14) in Uganda and 19.1% (4/21) in the United Republic of Tanzania. Conclusion Suboptimal registration of essential antimicrobials and over-registration of non-essential antimicrobials may encourage inappropriate use, especially since non-essential antimicrobials do not appear on national treatment guidelines. Countries should prioritize registration of the antimicrobial medicines on their essential medicines lists.
Supplemental material, JRS899308 Supplemental material for Will HPV vaccination prevent cervical ... more Supplemental material, JRS899308 Supplemental material for Will HPV vaccination prevent cervical cancer? by Claire P Rees, Petra Brhlikova and Allyson M Pollock in Journal of the Royal Society of Medicine
Background: Building appropriate levels of trust in pharmaceuticals is a painstaking and challeng... more Background: Building appropriate levels of trust in pharmaceuticals is a painstaking and challenging task, involving participants from different spheres of life, including producers, distributors, retailers, prescribers, patients and the mass media. Increasingly, however, trust is not just a national matter, but involves cross-border flows of knowledge, threats and promises. Methods: Data for this paper comes from the project ‘Tracing Pharmaceuticals in South Asia’, which used ethnographic fieldwork and qualitative interviews to compared the trajectories of three pharmaceuticals (Rifampicin, Oxytocin and Fluoxetine) from producer to patient in three sites (north India, West Bengal and Nepal) between 2005-08. Results: We argue that issues of trust are crucial in reducing the likelihood of appropriate use of medicines. Unlike earlier discussions of trust, we suggest that trust contexts beyond the patient-practitioner relationship are important. We illustrate these arguments through th...