Aim: We investigated the effectiveness of durvalumab post-concurrent CRT (cCRT) and post-sequenti... more Aim: We investigated the effectiveness of durvalumab post-concurrent CRT (cCRT) and post-sequential CRT (sCRT) versus cCRT and sCRT alone and compared these outcomes with the PACIFIC trial. Methods: Four cohorts of stage III NSCLC patients who received CRT were included: cCRT with and without durvalumab, sCRT with and without durvalumab. PFS and OS were analyzed using Cox regression. Results: Durvalumab improved PFS (cCRT: aHR = 0.69, sCRT: aHR = 0.71) and OS (cCRT: aHR = 0.71, sCRT: aHR = 0.32), although not all results were significant. PFS was longer in the real-world than in the trial, while OS did not differ. Conclusion: Durvalumab after CRT improved the survival outcomes. The difference between PFS in our study and the trial may be due to differences in follow-up methods.
Since 2006, the European conditional marketing authorization (CMA) aims to facilitate timely pati... more Since 2006, the European conditional marketing authorization (CMA) aims to facilitate timely patient access to medicinal products for which there is an unmet medical need by accepting less comprehensive data than normally required. The granting of CMA requires a positive benefit–risk balance, unmet medical needs to be fulfilled, likely submission of comprehensive data postauthorization, and the benefit of immediate availability to outweigh the risks of data noncomprehensiveness. Since its first use, more than half of all CMAs represent (hemato‐)oncology indications. Therefore, we aimed to investigate the conditions in which CMA has been applied for anticancer medicinal products and whether they have changed over time. We retrospectively assessed the European public assessment reports of the 30 anticancer medicinal products granted CMA in 2006–2020 (51% of all 59 CMAs). Comparison of 2006–2013 to 2014–2020 highlighted increased proportions of proactively requested CMAs (+40%), medici...
In the European Union (EU), the medicine regulatory system aims to protect and promote public hea... more In the European Union (EU), the medicine regulatory system aims to protect and promote public health by assessment of quality, safety and efficacy data before a marketing authorisation can be obtained and a medicine can be marketed. This so-called benefit-risk assessment is always based on partially incomplete knowledge and thus subject to uncertainty. Also, the context of use of medicines in clinical practice is ever-changing. Therefore, regulatory pathways and instruments have been put into place to allow for continuous evidence generation and subsequent decision-making about the benefit-risk balance of a medicine after it is authorised. The objective of this thesis was to provide insights into evidence generation on benefits and risks throughout the medicine lifecycle, and how it affects decision-making by regulatory and downstream decision-makers in the EU. This thesis first explores evidence generation for European regulatory decision-making based on three studies. Topics include the conditional marketing authorisation (CMA) pathway and its specific obligations for post-authorisation studies that are imposed to provide comprehensive evidence, as well as post-authorisation regulatory actions. The thesis then delves into the impact of evidence for regulatory decision-making on downstream decision-makers, whose decisions also affect patient access to medicines, based on another three studies. Topics include impact on decision-making by health technology assessment (HTA) agencies, which provide recommendations or decisions on reimbursement of medicines, and decision-making in clinical practice. Two studies focused specifically on the CMA pathway and its typical specific obligations for post-authorisation studies. Thereafter, the findings of the research presented in this thesis are placed in a broader perspective. This discussion revolves around the value of post-authorisation evidence generation for CMA medicines, the relative importance of studying both risk-related and benefit-related post-authorisation regulatory actions and associated learnings for regulatory decision-making, and the role of evidence generated for regulatory purposes in HTA and clinical practice. Additionally, the discussion puts forward aspects that enabled and strengthened the typical drug regulatory science studies that were performed for this thesis, as well as policy recommendations for regulatory, HTA and clinical practice decision-makers in line with the conclusions drawn throughout the thesis. Last, the thesis describes three important developments in the regulatory system that will affect future evidence generation and may draw from the learnings in this thesis: significant innovations in medicine development such as advanced therapy medicinal products, developments in types of evidence such as ‘real-world’ evidence, and developments in the regulatory assessment of evidence such as real-time monitoring of effectiveness and safety. The thesis’ overarching conclusion is that it is important to comprehensively consider multiple facets of evidence generation on benefits and risks of medicines: from the simultaneous generation of evidence concerning benefits and risks to the process of continued evidence generation throughout the medicine lifecycle, and how this affects decision-making by regulators, HTA agencies and physicians. It therewith provides a perspective on the evidence generation process, but also on drug regulatory science as a scientific field, including its role in evaluating the public health system and the methods that may be employed to perform this evaluation
Background: To minimise post-marketing uncertainties for products with a Conditional Marketing Au... more Background: To minimise post-marketing uncertainties for products with a Conditional Marketing Authorisation (CMA) in Europe, specific obligations (e.g. interventional and observational studies) are imposed as a condition to the marketing authorisation (MA). A yearly follow-up of these requirements and assessment of study results is conducted during annual renewal (AR). Objectives: To characterise changes in descriptions and due dates of obligations over time, and identify drug and obligation-related factors associated with these changes. Methods: We performed a retrospective cohort study of obligations imposed on the CMA of products licensed (excluding vaccines) since 2006 with at least one year follow-up or one AR (until 31/12/ 16). Changes in wording or due date of obligations were identified by comparing the MAs of products at granting, AR(s) and conversion of the CMA. Unconditional logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (CI)...
Cutaneous deep penetrating melanocytic neoplasms frequently simulate melanoma and might occasiona... more Cutaneous deep penetrating melanocytic neoplasms frequently simulate melanoma and might occasionally progress to metastatic melanoma. Distinguishing deep penetrating nevi (DPN) and deep penetrating melanocytomas (DPM) from malignant deep penetrating tumors (MDPT) is difficult based on histopathology alone, and diagnostic criteria for MDPT are currently lacking. Using a molecular workup, we aimed to provide readily available diagnostic tools for classification of deep penetrating tumors. We used clinical follow-up and Single Nucleotide Polymorphism (SNP) array for tumor classification of 20 deep penetrating neoplasms to identify associations with histopathological, immunohistochemistry, and NGS findings. Ten neoplasms were classified as MDPT, four as DPM, and six as DPN. Two MDPT showed metastases. The following parameters were statistically significantly associated with MDPT: severe nuclear atypia (risk ratio [RR] 2.9, p < 0.05), absence of a nevus component (RR 10.0, p = 0.04), positive PRAME expression (RR 9.0, p = 0.02), complete loss of p16 expression (RR 3.5, p = 0.003), TERT-p and APC mutations (RR 11.0, p = 0.01 and RR 2.7, p = 0.002, respectively), and ≥1 additional pathogenic mutation (RR 9.0, p = 0.02). Ki-67 expression ≥ 5% was not significantly associated with MDPTs, although it was <5% in all DPNs. Three MDPT did not show nuclear β-catenin expression despite having a CTNNB1 (n = 2) or an APC mutation (n = 1). Our findings suggest that complete loss of p16 and positive PRAME expression, a driver mutation in APC, ≥ 1 additional pathogenic mutation, especially in TERT-p, support an MDPT diagnosis in deep penetrating neoplasms. Besides severe nuclear atypia and possibly severe inflammation, we did not identify specific histopathological criteria for malignancy. Non-aberrant nuclear β-catenin expression might not exclude a deep penetrating signature in MDPT.
We aimed to determine whether uncertainties identified by the European Medicines Agency (EMA) wer... more We aimed to determine whether uncertainties identified by the European Medicines Agency (EMA) were associated with negative relative effectiveness assessments (REAs) and negative overall reimbursement recommendations by national health technology assessment (HTA) agencies. Therefore, we identified all HTA reports from Haute Autorité de Santé (HAS; France), National Institute for Health and Care Excellence (NICE; England/Wales), Scottish Medicine Consortium (SMC; Scotland), and Zorginstituut Nederland (ZIN; The Netherlands) for a cohort of innovative medicines that the EMA had approved in 2009 to 2010 (excluding vaccines). Uncertainty regarding pivotal trial methodology, clinical outcomes, and their clinical relevance were combined to reflect a low, medium, or high level of uncertainty. We assessed associations by calculating risk ratios (RRs) and 95% confidence intervals (CIs), and agreement between REA and overall reimbursement recommendation outcomes. We identified 36 medicines fo...
ABSTRACT Background: Prior studies investigated regulatory actions that reflected a negative impa... more ABSTRACT Background: Prior studies investigated regulatory actions that reflected a negative impact on drug risks. We aimed to evaluate occurrence of regulatory actions that reflected a negative or positive impact on benefits or risks, as well as relations between them. Research design and methods: We followed EMA-approved innovative drugs from approval (2009–2010) until July 2020 or withdrawal to identify regulatory actions. We assessed these for impact on benefits or risks and relations between actions. Additionally, we scrutinized drug lifecycles for time-variant characteristics that may contribute to specific patterns of regulatory actions. Results: We identified 14 letters and 361 label updates for 40 drugs. Of the label updates, 85 (24%) reflected a positive impact, mostly concerning indications, and 276 (76%) a negative impact, mostly adverse drug reactions. Many updates (54%) occurred simultaneously with other updates, also if these reflected a different impact. Furthermore, levels of patient exposure, innovativeness, needs for regulatory learning and unexpected risks may contribute to patterns of regulatory actions. Conclusions: Almost a quarter of regulatory actions reflected a positive impact on benefits and risks. Also, simultaneous learning about benefits and risks suggests an important role for drug development in risk characterization. These findings may impact regulatory analyses and decision-making.
Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagno... more Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect genome-wide copy number variations (CNVs) might provide a valuable tool to allow accurate classification as benign (nevus) or malignant (melanoma). However, the CNV cut-off value to distinguish intermediate lesions from melanoma is not well defined. We performed a systematic review and individual patient data meta-analysis to evaluate the use of CNVs to classify intermediate melanocytic lesions. A total of 31 studies and 431 individual lesions were included. The CNV number in intermediate lesions (median 1, interquartile range [IQR] 0–2) was significantly higher (p<0.001) compared to that in benign lesions (median 0, IQR 0–1) and lower (p<0.001) compared to that in malignant lesions (median 6, IQR 4–11). The CNV number displayed excellent ability to differentiate between intermediate and malignant lesions (0.90, 95% C...
International Journal of Health Policy and Management
Background: The European Medicines Agency (EMA) aims to resolve uncertainties associated with con... more Background: The European Medicines Agency (EMA) aims to resolve uncertainties associated with conditionally approved drugs by imposing post-approval studies. Results from these studies may be relevant for health technology assessment (HTA) organizations. This study investigated the role of regulator-imposed post-approval studies within HTA. Methods: For all conditionally approved drugs up to December 2018, regulator-imposed post-approval studies were identified from EMA’s public assessment reports. The availability for and inclusion of study results in relative effectiveness (re)assessments were analyzed for 4 European HTA organizations: NICE (National Institute for Health and Care Excellence, England/Wales), HAS (Haute Autorité de Santé, France), ZIN (Zorginstituut Nederland, the Netherlands) and the European Network for Health Technology Assessment (EUnetHTA, Europe). When study results became available between an HTA organization’s initial assessment and reassessment, it was eval...
Introduction
To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its ... more Introduction
To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its oral alternative, capecitabine, as first-line treatment in patients with colorectal cancer (CRC).
Methods
Patients treated with 5-FU or capecitabine for CRC between January 1, 2011 and December 31, 2013 in a teaching hospital in the Sydney metropolitan area, Australia were identified using the hospital’s database MOSAIQ®. The electronic medical record of each patient was manually reviewed to extract factors potentially affecting treatment choice. Logistic regression was used to assess which patient and/or treatment factors could explain the choice between 5-FU or capecitabine. Where it was available in the medical correspondence, the explicit reason for the choice made was extracted.
Results
170 CRC patients were included; 119 on 5-FU, and 51 on capecitabine. The odds of receiving capecitabine as a first-line treatment were positively associated with giving patients a choice in the decision (OR = 17.51, 95% CI: 5.37–57.08). Qualitative data suggest treatment choices were motivated by convenience (oral administration) and tolerability. Time from diagnosis to treatment commencement (OR = 1.02 per month, 95% CI 1.00–1.04) was also found to be positively associated with the choice of capecitabine. The odds of being treated with capecitabine were lower for patients who lived further from the treating hospital (OR = 0.22, 95% CI 0.05–0.94).
Conclusion
This study suggests that patient choice, favoring oral capecitabine over i.v. 5-FU, was a key factor influencing first-line treatment for CRC in this cohort. To respect their autonomy, patients should be involved in the clinical decision making process.
Aim: We investigated the effectiveness of durvalumab post-concurrent CRT (cCRT) and post-sequenti... more Aim: We investigated the effectiveness of durvalumab post-concurrent CRT (cCRT) and post-sequential CRT (sCRT) versus cCRT and sCRT alone and compared these outcomes with the PACIFIC trial. Methods: Four cohorts of stage III NSCLC patients who received CRT were included: cCRT with and without durvalumab, sCRT with and without durvalumab. PFS and OS were analyzed using Cox regression. Results: Durvalumab improved PFS (cCRT: aHR = 0.69, sCRT: aHR = 0.71) and OS (cCRT: aHR = 0.71, sCRT: aHR = 0.32), although not all results were significant. PFS was longer in the real-world than in the trial, while OS did not differ. Conclusion: Durvalumab after CRT improved the survival outcomes. The difference between PFS in our study and the trial may be due to differences in follow-up methods.
Since 2006, the European conditional marketing authorization (CMA) aims to facilitate timely pati... more Since 2006, the European conditional marketing authorization (CMA) aims to facilitate timely patient access to medicinal products for which there is an unmet medical need by accepting less comprehensive data than normally required. The granting of CMA requires a positive benefit–risk balance, unmet medical needs to be fulfilled, likely submission of comprehensive data postauthorization, and the benefit of immediate availability to outweigh the risks of data noncomprehensiveness. Since its first use, more than half of all CMAs represent (hemato‐)oncology indications. Therefore, we aimed to investigate the conditions in which CMA has been applied for anticancer medicinal products and whether they have changed over time. We retrospectively assessed the European public assessment reports of the 30 anticancer medicinal products granted CMA in 2006–2020 (51% of all 59 CMAs). Comparison of 2006–2013 to 2014–2020 highlighted increased proportions of proactively requested CMAs (+40%), medici...
In the European Union (EU), the medicine regulatory system aims to protect and promote public hea... more In the European Union (EU), the medicine regulatory system aims to protect and promote public health by assessment of quality, safety and efficacy data before a marketing authorisation can be obtained and a medicine can be marketed. This so-called benefit-risk assessment is always based on partially incomplete knowledge and thus subject to uncertainty. Also, the context of use of medicines in clinical practice is ever-changing. Therefore, regulatory pathways and instruments have been put into place to allow for continuous evidence generation and subsequent decision-making about the benefit-risk balance of a medicine after it is authorised. The objective of this thesis was to provide insights into evidence generation on benefits and risks throughout the medicine lifecycle, and how it affects decision-making by regulatory and downstream decision-makers in the EU. This thesis first explores evidence generation for European regulatory decision-making based on three studies. Topics include the conditional marketing authorisation (CMA) pathway and its specific obligations for post-authorisation studies that are imposed to provide comprehensive evidence, as well as post-authorisation regulatory actions. The thesis then delves into the impact of evidence for regulatory decision-making on downstream decision-makers, whose decisions also affect patient access to medicines, based on another three studies. Topics include impact on decision-making by health technology assessment (HTA) agencies, which provide recommendations or decisions on reimbursement of medicines, and decision-making in clinical practice. Two studies focused specifically on the CMA pathway and its typical specific obligations for post-authorisation studies. Thereafter, the findings of the research presented in this thesis are placed in a broader perspective. This discussion revolves around the value of post-authorisation evidence generation for CMA medicines, the relative importance of studying both risk-related and benefit-related post-authorisation regulatory actions and associated learnings for regulatory decision-making, and the role of evidence generated for regulatory purposes in HTA and clinical practice. Additionally, the discussion puts forward aspects that enabled and strengthened the typical drug regulatory science studies that were performed for this thesis, as well as policy recommendations for regulatory, HTA and clinical practice decision-makers in line with the conclusions drawn throughout the thesis. Last, the thesis describes three important developments in the regulatory system that will affect future evidence generation and may draw from the learnings in this thesis: significant innovations in medicine development such as advanced therapy medicinal products, developments in types of evidence such as ‘real-world’ evidence, and developments in the regulatory assessment of evidence such as real-time monitoring of effectiveness and safety. The thesis’ overarching conclusion is that it is important to comprehensively consider multiple facets of evidence generation on benefits and risks of medicines: from the simultaneous generation of evidence concerning benefits and risks to the process of continued evidence generation throughout the medicine lifecycle, and how this affects decision-making by regulators, HTA agencies and physicians. It therewith provides a perspective on the evidence generation process, but also on drug regulatory science as a scientific field, including its role in evaluating the public health system and the methods that may be employed to perform this evaluation
Background: To minimise post-marketing uncertainties for products with a Conditional Marketing Au... more Background: To minimise post-marketing uncertainties for products with a Conditional Marketing Authorisation (CMA) in Europe, specific obligations (e.g. interventional and observational studies) are imposed as a condition to the marketing authorisation (MA). A yearly follow-up of these requirements and assessment of study results is conducted during annual renewal (AR). Objectives: To characterise changes in descriptions and due dates of obligations over time, and identify drug and obligation-related factors associated with these changes. Methods: We performed a retrospective cohort study of obligations imposed on the CMA of products licensed (excluding vaccines) since 2006 with at least one year follow-up or one AR (until 31/12/ 16). Changes in wording or due date of obligations were identified by comparing the MAs of products at granting, AR(s) and conversion of the CMA. Unconditional logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (CI)...
Cutaneous deep penetrating melanocytic neoplasms frequently simulate melanoma and might occasiona... more Cutaneous deep penetrating melanocytic neoplasms frequently simulate melanoma and might occasionally progress to metastatic melanoma. Distinguishing deep penetrating nevi (DPN) and deep penetrating melanocytomas (DPM) from malignant deep penetrating tumors (MDPT) is difficult based on histopathology alone, and diagnostic criteria for MDPT are currently lacking. Using a molecular workup, we aimed to provide readily available diagnostic tools for classification of deep penetrating tumors. We used clinical follow-up and Single Nucleotide Polymorphism (SNP) array for tumor classification of 20 deep penetrating neoplasms to identify associations with histopathological, immunohistochemistry, and NGS findings. Ten neoplasms were classified as MDPT, four as DPM, and six as DPN. Two MDPT showed metastases. The following parameters were statistically significantly associated with MDPT: severe nuclear atypia (risk ratio [RR] 2.9, p < 0.05), absence of a nevus component (RR 10.0, p = 0.04), positive PRAME expression (RR 9.0, p = 0.02), complete loss of p16 expression (RR 3.5, p = 0.003), TERT-p and APC mutations (RR 11.0, p = 0.01 and RR 2.7, p = 0.002, respectively), and ≥1 additional pathogenic mutation (RR 9.0, p = 0.02). Ki-67 expression ≥ 5% was not significantly associated with MDPTs, although it was <5% in all DPNs. Three MDPT did not show nuclear β-catenin expression despite having a CTNNB1 (n = 2) or an APC mutation (n = 1). Our findings suggest that complete loss of p16 and positive PRAME expression, a driver mutation in APC, ≥ 1 additional pathogenic mutation, especially in TERT-p, support an MDPT diagnosis in deep penetrating neoplasms. Besides severe nuclear atypia and possibly severe inflammation, we did not identify specific histopathological criteria for malignancy. Non-aberrant nuclear β-catenin expression might not exclude a deep penetrating signature in MDPT.
We aimed to determine whether uncertainties identified by the European Medicines Agency (EMA) wer... more We aimed to determine whether uncertainties identified by the European Medicines Agency (EMA) were associated with negative relative effectiveness assessments (REAs) and negative overall reimbursement recommendations by national health technology assessment (HTA) agencies. Therefore, we identified all HTA reports from Haute Autorité de Santé (HAS; France), National Institute for Health and Care Excellence (NICE; England/Wales), Scottish Medicine Consortium (SMC; Scotland), and Zorginstituut Nederland (ZIN; The Netherlands) for a cohort of innovative medicines that the EMA had approved in 2009 to 2010 (excluding vaccines). Uncertainty regarding pivotal trial methodology, clinical outcomes, and their clinical relevance were combined to reflect a low, medium, or high level of uncertainty. We assessed associations by calculating risk ratios (RRs) and 95% confidence intervals (CIs), and agreement between REA and overall reimbursement recommendation outcomes. We identified 36 medicines fo...
ABSTRACT Background: Prior studies investigated regulatory actions that reflected a negative impa... more ABSTRACT Background: Prior studies investigated regulatory actions that reflected a negative impact on drug risks. We aimed to evaluate occurrence of regulatory actions that reflected a negative or positive impact on benefits or risks, as well as relations between them. Research design and methods: We followed EMA-approved innovative drugs from approval (2009–2010) until July 2020 or withdrawal to identify regulatory actions. We assessed these for impact on benefits or risks and relations between actions. Additionally, we scrutinized drug lifecycles for time-variant characteristics that may contribute to specific patterns of regulatory actions. Results: We identified 14 letters and 361 label updates for 40 drugs. Of the label updates, 85 (24%) reflected a positive impact, mostly concerning indications, and 276 (76%) a negative impact, mostly adverse drug reactions. Many updates (54%) occurred simultaneously with other updates, also if these reflected a different impact. Furthermore, levels of patient exposure, innovativeness, needs for regulatory learning and unexpected risks may contribute to patterns of regulatory actions. Conclusions: Almost a quarter of regulatory actions reflected a positive impact on benefits and risks. Also, simultaneous learning about benefits and risks suggests an important role for drug development in risk characterization. These findings may impact regulatory analyses and decision-making.
Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagno... more Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect genome-wide copy number variations (CNVs) might provide a valuable tool to allow accurate classification as benign (nevus) or malignant (melanoma). However, the CNV cut-off value to distinguish intermediate lesions from melanoma is not well defined. We performed a systematic review and individual patient data meta-analysis to evaluate the use of CNVs to classify intermediate melanocytic lesions. A total of 31 studies and 431 individual lesions were included. The CNV number in intermediate lesions (median 1, interquartile range [IQR] 0–2) was significantly higher (p<0.001) compared to that in benign lesions (median 0, IQR 0–1) and lower (p<0.001) compared to that in malignant lesions (median 6, IQR 4–11). The CNV number displayed excellent ability to differentiate between intermediate and malignant lesions (0.90, 95% C...
International Journal of Health Policy and Management
Background: The European Medicines Agency (EMA) aims to resolve uncertainties associated with con... more Background: The European Medicines Agency (EMA) aims to resolve uncertainties associated with conditionally approved drugs by imposing post-approval studies. Results from these studies may be relevant for health technology assessment (HTA) organizations. This study investigated the role of regulator-imposed post-approval studies within HTA. Methods: For all conditionally approved drugs up to December 2018, regulator-imposed post-approval studies were identified from EMA’s public assessment reports. The availability for and inclusion of study results in relative effectiveness (re)assessments were analyzed for 4 European HTA organizations: NICE (National Institute for Health and Care Excellence, England/Wales), HAS (Haute Autorité de Santé, France), ZIN (Zorginstituut Nederland, the Netherlands) and the European Network for Health Technology Assessment (EUnetHTA, Europe). When study results became available between an HTA organization’s initial assessment and reassessment, it was eval...
Introduction
To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its ... more Introduction
To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its oral alternative, capecitabine, as first-line treatment in patients with colorectal cancer (CRC).
Methods
Patients treated with 5-FU or capecitabine for CRC between January 1, 2011 and December 31, 2013 in a teaching hospital in the Sydney metropolitan area, Australia were identified using the hospital’s database MOSAIQ®. The electronic medical record of each patient was manually reviewed to extract factors potentially affecting treatment choice. Logistic regression was used to assess which patient and/or treatment factors could explain the choice between 5-FU or capecitabine. Where it was available in the medical correspondence, the explicit reason for the choice made was extracted.
Results
170 CRC patients were included; 119 on 5-FU, and 51 on capecitabine. The odds of receiving capecitabine as a first-line treatment were positively associated with giving patients a choice in the decision (OR = 17.51, 95% CI: 5.37–57.08). Qualitative data suggest treatment choices were motivated by convenience (oral administration) and tolerability. Time from diagnosis to treatment commencement (OR = 1.02 per month, 95% CI 1.00–1.04) was also found to be positively associated with the choice of capecitabine. The odds of being treated with capecitabine were lower for patients who lived further from the treating hospital (OR = 0.22, 95% CI 0.05–0.94).
Conclusion
This study suggests that patient choice, favoring oral capecitabine over i.v. 5-FU, was a key factor influencing first-line treatment for CRC in this cohort. To respect their autonomy, patients should be involved in the clinical decision making process.
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Papers by Lourens T Bloem
To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its oral alternative, capecitabine, as first-line treatment in patients with colorectal cancer (CRC).
Methods
Patients treated with 5-FU or capecitabine for CRC between January 1, 2011 and December 31, 2013 in a teaching hospital in the Sydney metropolitan area, Australia were identified using the hospital’s database MOSAIQ®. The electronic medical record of each patient was manually reviewed to extract factors potentially affecting treatment choice. Logistic regression was used to assess which patient and/or treatment factors could explain the choice between 5-FU or capecitabine. Where it was available in the medical correspondence, the explicit reason for the choice made was extracted.
Results
170 CRC patients were included; 119 on 5-FU, and 51 on capecitabine. The odds of receiving capecitabine as a first-line treatment were positively associated with giving patients a choice in the decision (OR = 17.51, 95% CI: 5.37–57.08). Qualitative data suggest treatment choices were motivated by convenience (oral administration) and tolerability. Time from diagnosis to treatment commencement (OR = 1.02 per month, 95% CI 1.00–1.04) was also found to be positively associated with the choice of capecitabine. The odds of being treated with capecitabine were lower for patients who lived further from the treating hospital (OR = 0.22, 95% CI 0.05–0.94).
Conclusion
This study suggests that patient choice, favoring oral capecitabine over i.v. 5-FU, was a key factor influencing first-line treatment for CRC in this cohort. To respect their autonomy, patients should be involved in the clinical decision making process.
To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its oral alternative, capecitabine, as first-line treatment in patients with colorectal cancer (CRC).
Methods
Patients treated with 5-FU or capecitabine for CRC between January 1, 2011 and December 31, 2013 in a teaching hospital in the Sydney metropolitan area, Australia were identified using the hospital’s database MOSAIQ®. The electronic medical record of each patient was manually reviewed to extract factors potentially affecting treatment choice. Logistic regression was used to assess which patient and/or treatment factors could explain the choice between 5-FU or capecitabine. Where it was available in the medical correspondence, the explicit reason for the choice made was extracted.
Results
170 CRC patients were included; 119 on 5-FU, and 51 on capecitabine. The odds of receiving capecitabine as a first-line treatment were positively associated with giving patients a choice in the decision (OR = 17.51, 95% CI: 5.37–57.08). Qualitative data suggest treatment choices were motivated by convenience (oral administration) and tolerability. Time from diagnosis to treatment commencement (OR = 1.02 per month, 95% CI 1.00–1.04) was also found to be positively associated with the choice of capecitabine. The odds of being treated with capecitabine were lower for patients who lived further from the treating hospital (OR = 0.22, 95% CI 0.05–0.94).
Conclusion
This study suggests that patient choice, favoring oral capecitabine over i.v. 5-FU, was a key factor influencing first-line treatment for CRC in this cohort. To respect their autonomy, patients should be involved in the clinical decision making process.