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Press release: Forced switch Thyrax leads to problems

Research confirms: concerns were justified

Today the results of the study into the consequences of switching from Thyrax to other brands of levothyroxine were published. Last year, 350.000 patients who used Thyrax were forced to switch to other brands of levothyroxine. The current study shows that the risk of an overdose after switching is high.

Please click here to read more (Dutch only)


Improvements in the treatment of high-cardiovascular-risk patients in the Netherlands are needed

Only 67% of high-cardiovascular-risk patients are treated with lipid-modifying therapy (LMT), of which only 7% used a high-potency statin. Among LMT users, 69% of those taking high-potency statins, 70% taking standard-potency statins, and 20% receiving non-statin LMTs attains an LDL-C goal <100 mg/dL. This was found in a study recently published in Clinical Therapeutics. In this study the use of lipid-modifying therapy and attainment of LDL-C goals were investigated in a population at high cardiovascular risk, using data from the PHARMO Database Network. Results suggest that improvements in the treatment of cardiovascular disease in the Netherlands are needed because many high-cardiovascular-risk patients are not being treated with the maximally tolerated dose of statin. Increased use of statins and LMTs overall, as well as increased high-potency statin use, may be required to reduce cardiovascular risk in this population, and if that does not suffice, ultimately the addition of newer therapeutic options might be needed.

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No additional survival benefit in colorectal cancer patients using both aspirin and a non-aspirin thrombocyte aggregation inhibitor

Aspirin use after diagnosis of colorectal cancer is associated with a significantly lower mortality rate and this effect remains significant after adjusting for potential confounders. No additional survival benefit is observed in patients using both aspirin and a non-aspirin thrombocyte aggregation inhibitor (TAI). This was concluded in a study recently published in the European Journal of Cancer. In this study survival of patients using aspirin or aspirin in combination with non-aspirin TAI after diagnosis of colorectal cancer was compared with non-users, using linked data from the PHARMO Database Network and the Netherlands Comprehensive Cancer Organisation. In the future, due to new guidelines, it will be possible to analyse patients that used exclusively non-aspirin TAI. Further research is encouraged to reveal the interaction between thrombocytes and cancer. It is important to focus on novel thrombocyte-targeted anti-cancer therapies.

To read more, please click here.


No association between beta-blocker use and colorectal cancer prognosis

No beneficial effect of beta-blocker use on colorectal cancer (CRC) prognosis is found in a large population-based study recently published in the International Journal of Cancer. Neither for specific stage groups nor for specific types of beta-blockers. In this study it was investigated whether pre- or post-diagnostic use of β1-receptor selective and non-selective beta-blockers was associated with improved overall survival after CRC, using linked data from the PHARMO Database Network and the Netherlands Cancer Registry. As some aspects such as confounding by indication of beta-blocker treatment and confounding by disease severity can only partially be addressed in pharmacoepidemiological studies, a final conclusion on a possible effect of beta-blocker use on cancer prognosis can only be drawn after results from the currently ongoing randomized trials will be available.

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Increased risk of urinary tract infections during antipsychotic use

Older women using antipsychotics have an increased risk of uncomplicated urinary tract infections (UTIs), especially in the first week of treatment. This was concluded in a study recently published in Maturitas. In this study the incidence of UTIs, as defined by use of nitrofurantoin, was determined in women during current and past use of antipsychotic drugs, using the PHARMO Database Network in the Netherlands. Clinicians should be alert to the occurrence of UTIs after the start of an antipsychotic drug, especially in the first week. Further research is necessary to confirm these findings and establish whether this is also the case for men using antipsychotics and for complicated UTIs.

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Greater reduction in HbA1c when using basal insulin or insulin glargine compared to DPP-4 inhibitors

The reduction in HbA1c is greater in patients starting basal insulin or insulin glargine compared to DPP-4-inhibitors. This was concluded in a study recently published in Nederlands Tijdschrift voor Diabetologie using linked data from out-patient pharmacies and clinical laboratories from the PHARMO Database Network. A sensitivity analysis was performed on patients matched on baseline HbA1c and gender. When matching, only insulin glargine had a greater reduction in HbA1c. Improved glycemic control will lead to fewer hospitalisations, reduced healthcare costs and improved quality of life.

To read more, please click here.


Metformin use does not reduce risk of gastrointestinal cancer

Current use of metformin is not associated with a reduced risk of gastrointestinal (GI) cancer. This was concluded in a study recently published in Cancer Prevention Research. In this study the risk of GI cancer was evaluated in patients with type 2 diabetes mellitus using metformin compared to users of other non-insulin anti-diabetic drugs. Linked data from the PHARMO Database Network and the Eindhoven area of the Netherlands Cancer Registry were used and a time-varying approach was applied to determine exposure, which minimises exposure misclassification and time-related bias. The results of this study are in line with recent publications and highlight that methodological standards for drug exposure definitions should be met in observational studies. Future meta-analyses on the risk of cancer with use of metformin would benefit from an in-depth description of possible biases and confounding in all included studies, and by performing stratified analyses including only studies with a low level of confounding and bias.

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No association between overall survival, pancreatic cancer and metformin use

The use of metformin is not associated with improved overall survival in patients with pancreatic cancer. This was concluded in a study recently published in Medicine. Overall survival of patients with pancreatic cancer using metformin was compared with nonusers and with patients using sulfonylurea derivatives and did not show any association. Linked data from the PHARMO Database Network and the Eindhoven Cancer Registry were used. This study does not exclude the opportunity that metformin could be a valuable adjuvant therapy in other cancer types or only in patients with resectable, early stage pancreatic cancer. Nowadays, new oncology drugs are very expensive and drug repurposing is an attractive strategy to offer more effective options for patients with cancer

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Much variety in chemotherapy treatment patterns for ovarian cancer, predominantly in subsequent treatment lines

Chemotherapy treatment for ovarian cancer (OC) is diverse, predominantly in later lines of treatment. There is much practice variation in treatment as soon as platinum-based chemotherapy is no longer the treatment of choice, and many different (single) agents are being used from that point onwards. This was concluded in a study recently published in Medical Oncology. In this study patterns of chemotherapy and other systemic treatments among patients with OC in daily clinical practice in the Netherlands were described and survival outcomes following subsequent lines of treatment were evaluated. Linked data from the PHARMO Database Network and the Eindhoven Cancer Registry were used. With various new treatment options becoming available for the treatment of OC in the near future, including targeted therapies, the importance of clinical guidance is unmistakable. In disease areas such as OC, where patient heterogeneity warrants a level of individualised care, clear guidelines should prevent arbitrariness while ensuring that physicians can properly choose the most suitable treatment for each individual patient.

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BRAF and KRAS mutation status precluded as marker for individualized treatment with aspirin in patients with colon cancer

BRAF mutation status and KRAS mutation status are not distinctive in the association between low-dose aspirin use and a survival benefit in patients with colon cancer. This was concluded in a study recently published in PLoS One. This study investigated whether the survival benefit observed in patients with colon cancer using aspirin could be associated with BRAF or KRAS mutational status. Data on low dose aspirin use, derived from the PHARMO Database Network, were linked to the Eindhoven Cancer Registry. The results preclude BRAF and KRAS mutation status to be used as a marker for individualized treatment with aspirin, if aspirin becomes regular adjuvant treatment for colon cancer patients in the future.

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No decrease of preventable hospitalisations related to medication use in the Netherlands

In 2004 and 2008 studies showed that approximately 10.000-16.000 of the acute hospitalisations were related to medication and potentially preventable. The Dutch Ministry of Health, Welfare and Sport drew up recommendations (HARM-Wrestling) in 2009, aiming to decrease of the potential preventable hospitalisations related to medication. The results of the follow-up study (“Vervolgonderzoek Medicatieveiligheid”), which was commissioned by the ministry, are now available. The conclusions of the project team are that the recommendations are not adequately implemented and there is no decrease of preventable hospitalisations related to medication.

To read more, please click here.


Increased prevalence of diabetes in the Netherlands is only partly explained by changes in age and gender over time

 The prevalence of diabetes in the Netherlands increased from 1.8% in 1999 to 4.9% in 2014. Only half of this increase was explained by changes in age and gender over time. This was found in a study recently published in Nederlands Tijdschrift voor Geneeskunde using data from out-patient pharmacies in the PHARMO Database Network. To temper the increasing prevalence of diabetes, it is essential to gain more insight into the other factors responsible for the increase.

To read more, please click here.


Effect of low-dose aspirin use on survival of patients with gastrointestinal malignancies; an observational study

Aspirin use after diagnosis of gastrointestinal malignancies is associated with improved overall survival. The effect is most marked for tumours arising from the oesophagus, colon, rectum and hepatobilliary tract.
This observation was made in a study recently published in the British Journal of Cancer. Survival of patients who used aspirin after diagnosis of a gastrointestinal cancer vs nonusers was determined using the PHARMO Database Network linked to the Eindhoven Cancer Registry.
These results offer direction towards future studies, both in terms of new randomised controlled trials as well as further studies to identify biomarkers that predict response to aspirin.

To read more, please click here.


Explaining the decline in coronary heart disease mortality in the Netherlands between 1997 and 2007

Coronary heart disease (CHD) mortality has recently halved in the Netherlands. Equally large contributions have come from the increased use of acute and secondary prevention treatments and from improvements in population risk factors (including primary prevention treatments). This was concluded in a study recently published in PloS One. With nationwide information from several data sources including the PHARMO Database Network, the number of CHD deaths prevented or postponed was calculated using the IMPACT-SEC model. The observed positive trends however, have been negated by substantial increases in obesity and diabetes, which represent a major challenge for future, more effective prevention policies.

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Propranolol and survival from breast cancer: a pooled analysis of European breast cancer cohorts

Use of propranolol or non-selective beta-blockers was not associated with improved survival of breast cancer patients. This was concluded from a pooled analysis of eight cohorts of breast cancer patients from across Europe and recently published in Breast Cancer Research. Analyses were performed for propranolol or non-selective beta-blocker use before as well after breast cancer diagnosis, and for breast cancer-specific and all-cause mortality. Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. However, the results of this study do not support the decision on whether to conduct large phase 3 randomised controlled trials of propranolol as adjuvant cancer therapy in breast cancer patients.

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Asthma-related outcomes in patients initiating extrafine ciclesonide or fine-particle inhaled corticosteroids

Initiation of inhaled corticosteroids (ICS) with extrafine ciclesonide is associated with better 1-year asthma outcomes and fewer changes to therapy in that year, than initiation with fine-particle ICS. This was concluded in a study recently published in Allergy, Asthma & Immunology Research. In this study the rate of severe exacerbations, risk-domain asthma control and overall asthma control were determined in patients receiving a first prescription of ICS, using the PHARMO Database Network in the Netherlands. More real-life observational or randomized controlled studies in other patient populations and for different extrafine-particle ICS are needed to further explore the findings of this study.

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Anticoagulant treatment after VTE in the Netherlands: A retrospective cohort study

Treatment after venous thromboembolism (VTE) as captured in observational healthcare data generally follows the Dutch guidelines, except for the duration of low-molecular-weight heparin treatment, which was longer than recommended. This was concluded in a study recently published in Jacobs Journal of Hematology. Initial anticoagulant treatment after VTE was determined using the PHARMO Database Network in the Netherlands. The observation of shorter anticoagulant treatment among patients with recurrent VTE compared to patients with no recurrence may indicate that anticoagulant treatment was not optimal for these patients.

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The effect of switching from Thyrax Duotab to other brands of levothyroxine:
First results and interim advice

The stock-out of Thyrax Duotab in the Netherlands forced thousands of Thyrax Duotab users to switch to other brands of levothyroxine.

The Dutch Society for Endocrinology (NVE) and the Dutch Thyroid Organisation (SON) initiated studies on the consequences of the stock-out of Thyrax Duotab in the Netherlands. These studies are conducted by the PHARMO Institute and the Netherlands Institute for Health Services Research (NIVEL).

The first results of these studies show to the effect of switching from Thyrax Duotab to other brands of levothyroxine on thyroid-stimulating hormone (TSH) values. The interim advice from the advisory board following these results can be found here (Dutch only).


Characterisation and cholesterol management in patients with cardiovascular events and/or type 2 diabetes in the Netherlands

Over 40% of monitored patients in the Netherlands with established cardiovascular disease or type 2 diabetes mellitus and LDL-cholesterol levels > 1.8 mmol/L did not reach the target of 2.5 mmol/L, despite receiving lipid modifying treatment. This was concluded in a study recently published in Current Medical Research and Opinion. In this cross-sectional descriptive study, using linked pharmacy, hospitalisation and GP data from the PHARMO Database Network, characteristics and cholesterol management in 2010 of patients with high cardiovascular risk were determined. Findings suggest that management of hypercholesterolemia and other cardiovascular risk factors should be optimized to improve cardiovascular outcomes.

To read more, please click here.


Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study

Current use of both COX 2 inhibitors and traditional NSAIDs is associated with an increased risk of heart failure. The magnitude of the association varies between individual NSAIDs and is dose dependent. This was concluded in a study recently published in the British Medical Journal. The study was based on five electronic healthcare databases from four European countries: the Netherlands, Italy, Germany, and the UK. Among patients starting NSAID treatment in 2000-2010, the period, type and dose of NSAID use was compared between patients admitted for heart failure during follow-up and matched controls without such admission. Because any potential increased risk could have a considerable impact on public health, the risk effect estimates provided by this study may help inform both clinicians and health regulators.

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Rates of prostate surgery and acute urinary retention for benign prostatic hyperplasia in men treated with dutasteride or finasteride

The risk of undergoing BPH-related prostate surgery was lower among men using dutasteride compared to men using finasteride. This was concluded in a study recently published in BMC Urology. In this study, drug dispensing and hospitalisation data from the PHARMO Database Network was used. The majority of dutasteride or finasteride users started treatment in combination with an alpha-blocker. The lower risk of undergoing BPH-related prostate surgery among men using dutasteride was also seen when stratifying by monotherapy or combination therapy, but was only present among men treated by urologists. The number of men admitted for acute urinary retention was too low for comparative analyses.

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Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes

There is no evidence of an association between the risk of bladder cancer and the use of pioglitazone compared to the use of other antidiabetic drugs (HR 0.99 (95% CI 0.75 to 1.30)). This was concluded in a recent publication in the British Medical Journal, reporting the findings of a Post Authorisation Safety Study (PASS) imposed by the European Medicines Agency (EMA), after concerns had arisen around a potential increased risk of bladder cancer with pioglitazone use. Four database partners (PHARMO Institute from the Netherlands, EPID Research from Finland, Karolinska Institutet from Sweden and CPRD from the UK) contributed 6 cohorts to the study. Although results differed per cohort, no significant association was found in either the pooled analysis or the meta-analysis. These results provide important additional information on the safety of pioglitazone use in Europe.

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Drug dispensings among elderly in the year before colon cancer diagnosis versus matched cancer-free controls

Elderly colon cancer patients have more drug dispensings from out-patient pharmacies during the year before diagnosis as compared to a matched cancer-free control group, which could be caused by a higher level of comorbidity. This was concluded in a study recently published in the Journal of Clinical Pharmacy and Therapeutics. For this study, data from the Cancer Registry linked to the PHARMO Database Network was used. The ten most commonly used types of drugs were drugs for constipation, antithrombotics, drugs for acid-related disorders, antibacterials, renin–angiotensin system related agents, beta-blockers, lipid-modifying agents, diuretics, psycholeptics and antianaemics. Drugs for constipation, drugs for acid-related disorders, antianaemics, beta-blockers, antibacterials and psycholeptics were dispensed to an increasing proportion of cases in the last three months before colon cancer diagnosis.

Insight in commonly used drugs may trigger general practitioners and medical specialists to further evaluate the patient.

To read more, please click here.


Prescription behavior for gastroprotective drugs in new users as a result of communications regarding clopidogrel – proton pump inhibitor interaction

There is a significant effect on prescription and subsequent dispensing behavior for gastroprotective drugs among patients in the Netherlands starting clopidogrel due to statements and direct healthcare professional communications (DHPC or “Dear Doctor” letter) by the regulatory agencies. However, the effect was hesitant, not fully complying to the official advices. This was concluded in a study recently published in Pharmacology Research & Perspectives.

In this study the association was investigated between the various communications on the safety of the combined use of clopidogrel and PPIs and the prescribing behavior   in the years 2008–2011 as deduced from dispensing records of out-patient pharmacies in the PHARMO Database Network. Although the place in therapy of clopidogrel will be repositioned to specific – smaller – groups of patients, prescribing the drug still needs to be done in a safe way, taking into account all available safety information and weighing pros and cons of the message. Lessons learned in this study should be applied to managing drug safety information in general.

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Post-authorization safety study comparing quetiapine to risperidone and olanzapine

Quetiapine was found to be associated with lower incidence rates of extrapyrimidal symptoms (EPS) and diabetes mellitus compared to olanzapine. Compared to risperidone, EPS rates were lower, but failed suicide attempt rates were higher with quetiapine. This was concluded in a post-authorisation safety study imposed by EMA as part of the EU approval for the bipolar depression application of quetiapine, and recently published in Human Psychopharmacology.
The study shows the relative safety of the most frequently used second generation antipsychotics as they are used in daily clinical practice, which may differ from expectations based on label information both with respect to dosing and indication. The study therefore provides relevant information adding to information gathered in psychiatric hospital and trial settings.

To read more, please click here


The PHARMO Institute and X-IS have joined forces:

PHARMO and X-IS created a proof of concept that provides insight into the use and outcomes of expensive medicines in hospitals!

By linking data from DICA registrations, pharmaceuticals and financial information we provide hospital management, medical specialists and hospital pharmacist integrated insight into the use and outcomes of expensive medicines within and between hospitals. For more information click here (only in Dutch).


PHARMO presentation “Expensive medicine linked to quality registry: insight into costs and appropriate use” at the DICA convention on the 16th of June in Amsterdam

In this session we share with you the first results of the Rx-pilot from DICA, the PHARMO Institute and X-IS. During the Rx-pilot data from the Dutch Surgical Clinical Auditing (DSCA), hospital pharmacy and finance of one hospital were linked. This provides new insights into prescribed medication on a patient level, in what quantity, and the similarities and differences between patient groups (i.e. tumour location, ASA score, age).  This could improve the efficient use of expensive medicine in all Dutch hospitals. For more information click here.


Effectiveness of initiating extrafine-particle versus fine-particle inhaled corticosteroids as asthma therapy in the Netherlands

Patients prescribed extrafine-particle inhaled corticosteroids (ICS) had significantly lower rates of exacerbations, and significantly higher odds of achieving asthma control and treatment stability than those prescribed fine-particle ICS, and this occurred at lower prescribed doses. These results are coming from a study recently published in the BMC Pulmonary Medicine. The study included patients with asthma registered in the General Practitioner Database of the PHARMO Database Network. Findings contradictresults from randomised controlled trials including selected asthma patients. Additional comparative effectiveness studies in real-life asthma patients are required to better understand the differential effects of extrafine-particle versus fine-particle ICS , especially regarding possible subgroup specificities.

To read more, please click here.


Webinar on sequential treatment analysis given by Edith Heintjes, Scientific Research Manager at the PHARMO Institute

On March 23rd, 2016 Edith Heintjes, PhD, gave a webinar on sequential treatment analysis.
The presentation on “Challenges of sequential treatment analysis” focused on the methodological challenges of patient centric treatment pattern analysis. It was part of a webinar organised by PHUSE to promote its new Real World Evidence (RWE) stream. PHUSE is a global platform for the discussion of topics encompassing the work of Data Managers, Biostatisticians, Statistical Programmers and Clinical IT professionals.

If you weren’t able to attend, the webinar has been uploaded on the PHUSE website for later viewing. To view the webinar please click here. The presentation by Edith Heintjes starts at 19:20 minutes into the recording, and lasts 30 minutes, after which some questions from the viewers were answered.
If you have any questions regarding this presentation or if you are interested to find out how we can assist you in answering your research questions with our expertise, please contact us at and we will reach out to you. 


Prescribing pattern of antipsychotic drugs during the years 1996-2010: a population-based database study in Europe with a focus on torsadogenic drugs.

Use of antipsychotic drugs with torsadogenic potential was substantial in Europe during the years 1996-2010, in spite of increasing concerns about their arrhythmogenic potential. This use was even greater in elderly patients, who are at higher risk of sudden cardiac death. This was concluded in a study recently published in the British Journal of Clinical Pharmacology. The study cohort was selected based on prescription/dispensing data from seven European healthcare databases from Denmark, Germany, Italy, the Netherlands and the UK. Findings suggest that the wide use of antipsychotic drugs in elderly patients should be carefully taken into account, given their higher risk of ventricular arrhythmias.

To read more, please click here


Muscokeletal hospital admission and surgical procedure rates among patients treated for rheumatoid arthritis in the Netherlands

In the past decade, muscoskeletal surgery rates among rheumatoid arthritis (RA) patients in the Netherlands halved. This was concluded in a study recently published in the Journal of Orthopedics and Rheumatology. In this study the hospital admission and musculoskeletal surgery rates in patients treated for RA were determined in the PHARMO Database Network between 1999 and 2012. The largest reduction in surgery rates occurred during the period when biological disease-modifying anti-rheumatic drugs (DMARD) were introduced. However, surgical rates remained more than twice as high for patients with RA compared to reference subjects without RA.

To read more, please click here.


Should aspirin and nonsteroidal anti-inflammatory drugs be used to increase the overall survival of patients with oesophageal cancer?

Postdiagnosis aspirin use might be associated with a higher survival rate in oesophageal cancer patients. This was shown by a study performed at Leiden University Medical Center with data from the PHARMO Database Network linked to the Eindhoven Cancer Registry. The study, recently published in the British Journal of Cancer, presented a possible association between postdiagnosis aspirin use and overall survival in patients with oesophageal cancer. The effect seemed to be aspirin-specific as the postdiagnosis use of NSAIDs had no significant effect on outcome.

To read more, please click here


The availability of information on impaired renal function in the community pharmacy, a descriptive pilot study

For only 37% of patients with available information on impaired renal function in the PHARMO Database Network this information was also available in their community pharmacy. This was 52% when also risk medication was used. This was concluded in a study recently published in the Journal of Nephrology and Renal Therapy. In this study the availability of renal function tests in Dutch community pharmacies was assessed, using data on laboratory assessments in the PHARMO Database Network as golden standard. Findings suggest that available information on renal function in community pharmacies is insufficient, which hinders effective medication surveillance.

To read more, please click here.


Use of oral contraceptives in three European countries: a population-based multi-database study.

Second-generation oral contraceptives (OC) are common in the Netherlands, but in the UK and even more so in Italy, many women use third- or fourth-generation OC. This was concluded in a study among 2.4 million women which was recently published in The European Journal of Contraception & Reproductive Health Care. Third-generation and possibly also fourth-generation pills have been associated with a higher risk of venous thrombosis than second-generation progestogens. The prevalent use of third- or fourth-generation OC as observed in the UK and Italy suggest that more risk minimisation measures are warranted.

To read more, please click here