Development of subfamily-based consensus PCR assays for the detection of human and animal herpesviruses.

Consensus PCR assays that can be used to sensitively detect several herpesvirus (HV) species across the different subfamilies were developed in this study. Primers containing degenerate bases were designed to amplify regions of the DNA polymerase (DPOL) gene of alpha- and gamma-HVs, and the glycoprotein B (gB) gene of beta-HVs in a singleplex, non-nested touchdown PCR format. The singleplex touchdown consensus PCR (STC-PCR) was used to amplify the DNA of eight human and 24 animal HVs. The assay was able to detect the lowest DNA dilution of 10-5 for alpha-HVs and 10-3 for beta- and gamma-HVs. In comparison, lowest detection limits of 10-5, 10-3, and 10-2 were obtained for alpha-, beta-, and gamma-HVs respectively when a nested PCR was used. The findings in this study suggest that the STC-PCR assays can be employed for the molecular surveys and clinical detection of novel and known HVs.

A long-term follow-up of safety and clinical efficacy of NTCELL® [Immunoprotected (Alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease.

INTRODUCTION: In 2019, we published the results of a Phase IIb randomized controlled trial of putaminal encapsulated porcine choroid plexus cell (termed NTCELL®) administration in patients with Parkinson's disease. This study failed to meet its primary efficacy end-point of a change in UPDRS part III score in the 'off' state at 26-weeks post-implant. However, a number of secondary end-points reached statistical significance. We questioned whether with longer follow-up, clinically significant improvements would be observed. For this reason, we decided to follow-up all patients periodically to week 104. Herein, we report the results of this long-term follow-up. METHODS: All 18 patients included in the original study were periodically re-assessed at weeks 52, 78 and 104 post-implant. At each time-point, motor and non-motor function, quality of life and levodopa equivalent daily dose was assessed using a standardized testing battery. RESULTS: At week 104, no significant differences in UPDRS part III scores in the 'off' state were observed in any of the treatment groups compared to baseline. Only a single serious adverse event - hospitalisation due to Parkinson's disease rigidity not responding to changes in medications - was considered potentially related to the implant procedure. There was no evidence of xenogeneic viral transmission. CONCLUSION: Un-blinded, long-duration follow-up to week 104 post-implantation showed no evidence that putaminal NTCELL® administration produces significant clinical benefit in patients with moderately advanced Parkinson's disease.

Safety and acceptability of clozapine and risperidone in progressive multiple sclerosis: a phase I, randomised, blinded, placebo-controlled trial.

OBJECTIVE: Because clozapine and risperidone have been shown to reduce neuroinflammation in humans and mice, the Clozapine and Risperidone in Progressive Multiple Sclerosis (CRISP) trial was conducted to determine whether clozapine and risperidone are suitable for progressive multiple sclerosis (pMS). METHODS: The CRISP trial (ACTRN12616000178448) was a blinded, randomised, placebo-controlled trial with three parallel arms (n=12/arm). Participants with pMS were randomised to clozapine (100-150 mg/day), risperidone (2.0-3.5 mg/day) or placebo for 6 months. The primary outcome measures were safety (adverse events (AEs)/serious adverse events (SAE)) and acceptability (Treatment Satisfaction Questionnaire for Medication-9). RESULTS: An interim analysis (n=9) revealed significant differences in the time-on-trial between treatment groups and placebo (p=0.030 and 0.025, clozapine and risperidone, respectively) with all participants receiving clozapine being withdrawn during the titration period (mean dose=35±15 mg/day). Participants receiving clozapine or risperidone reported a significantly higher rate of AEs than placebo (p=0.00001) but not SAEs. Specifically, low doses of clozapine appeared to cause an acute and dose-related intoxicant effect in patients with pMS who had fairly severe chronic spastic ataxic gait and worsening over all mobility, which resolved on drug cessation. INTERPRETATION: The CRISP trial results suggest that patients with pMS may experience increased sensitivity to clozapine and risperidone and indicate that the dose and/or titration schedule developed for schizophrenia may not be suitable for pMS. While these findings do not negate the potential of these drugs to reduce multiple sclerosis-associated neuroinflammation, they highlight the need for further research to understand the pharmacodynamic profile and effect of clozapine and risperidone in patients with pMS. TRIAL REGISTRATION NUMBER: ACTRN12616000178448.

A phase IIb, randomised, double-blind, placebo-controlled, dose-ranging investigation of the safety and efficacy of NTCELL® [immunoprotected (alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease.

INTRODUCTION: Regenerative therapies in Parkinson's disease aim to slow neurodegeneration and re-establish damaged neuronal circuitry. Neurotrophins are potent endogenous regulators of neuronal survival, development and regeneration. They represent an attractive regenerative treatment option in Parkinson's disease. Porcine choroid plexus produces a number of neurotrophins, and can be safely delivered to the striatum in an encapsulated formulation (termed NTCELL®) to protect them from immune attack. NTCELL® has shown regenerative potential in animal models of stroke, Huntington's disease and Parkinson's disease. Following promising results from an initial open label safety study of intra-striatal delivery of NTCELL® in human subjects, we sought to specifically investigate the safety and efficacy of NTCELL® for the treatment of Parkinson's disease. METHODS: 18 patients aged 56-65 years with idiopathic Parkinson's disease of at least 5 years duration were randomised to receive either sham surgery (general anaesthesia and partial thickness burr holes) or intra-striatal delivery of NTCELL® (the 3 groups in the treatment arm receiving incremental NTCELL® doses). RESULTS: At 26 weeks, we found no significant difference in total UPDRS scores ('on' and 'off'), UPDRS motor scores ('on' and 'off'), PDQ-39, UDysRS, timed walk or modified Hoehn and Yahr stage between patients implanted with NTCELL® and patients undergoing sham procedure. There were no serious adverse events or xenogeneic viral transmission during the study. CONCLUSION: The study did not meet its primary efficacy end-point of a change in UPDRS at 26 weeks post-intervention compared with baseline. Stereotactic NTCELL® implantation was safe and well tolerated.

Differential Gene Expression in Menstrual Endometrium From Women With Self-Reported Heavy Menstrual Bleeding.

Heavy menstrual bleeding (HMB) is a significant social and public health issue for menstruating women. Development of targeted treatments has been limited by poor understanding of local mechanisms underlying HMB. We aimed to determine how gene expression differs in menstrual phase endometrium from women with HMB. Menstrual phase endometrial biopsies were collected from women with (n = 7) and without (n = 10) HMB (regular menstrual cycles, no known pelvic pathology), as well as women with uterine fibroids (n = 7, n = 4 had HMB). Biopsies were analyzed using Illumina Sentrix Human HT12 arrays and data analyzed using "Remove Unwanted Variation-inverse". Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery v6.7 were used to identify gene pathways, functional gene clusters, and upstream regulators specific to the clinical groupings. Individual genes of interest were examined using quantitative polymerase chain reaction. In total, 829 genes were differentially expressed in one or more comparisons. Significant canonical pathways and gene clusters enriched in controls relative to both HMB and fibroid groups suggest the mechanisms responsible for HMB include modifications of the endometrial inflammatory or infection response. In contrast, differentially expressed genes in women with fibroids suggest modifications of hemoglobin, antigen processing, and the major histocompatibility complex (class II, beta chain) activity. In conclusion, HMB associated with fibroids may be regulated by different endometrial mechanisms from HMB in women without fibroids and from normal menstrual bleeding. These novel data provide numerous testable hypotheses that will advance our understanding of the mechanisms responsible for HMB.

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and Cmax and was slowly eliminated (mean t1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues.

Identification of genes differentially expressed in menstrual breakdown and repair.

STUDY QUESTION: Does the changing molecular profile of the endometrium during menstruation correlate with the histological profile of menstruation. SUMMARY ANSWER: We identified several genes not previously associated with menstruation; on Day 2 of menstruation (early-menstruation), processes related to inflammation are predominantly up-regulated and on Day 4 (late-menstruation), the endometrium is predominantly repairing and regenerating. WHAT IS KNOWN ALREADY: Menstruation is induced by progesterone withdrawal at the end of the menstrual cycle and involves endometrial tissue breakdown, regeneration and repair. Perturbations in the regulation of menstruation may result in menstrual disorders including abnormal uterine bleeding. STUDY DESIGN, SIZE DURATION: Endometrial samples were collected by Pipelle biopsy on Days 2 (n = 9), 3 (n = 9) or 4 (n = 6) of menstruation. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA was extracted from endometrial biopsies and analysed by genome wide expression Illumina Sentrix Human HT12 arrays. Data were analysed using 'Remove Unwanted Variation-inverse (RUV-inv)'. Ingenuity pathway analysis (IPA) and the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.7 were used to identify canonical pathways, upstream regulators and functional gene clusters enriched between Days 2, 3 and 4 of menstruation. Selected individual genes were validated by quantitative PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 1753 genes were differentially expressed in one or more comparisons. Significant canonical pathways, gene clusters and upstream regulators enriched during menstrual bleeding included those associated with immune cell trafficking, inflammation, cell cycle regulation, extracellular remodelling and the complement and coagulation cascade. We provide the first evidence for a role for glutathione-mediated detoxification (glutathione-S-transferase mu 1 and 2; GSTM1 and GSTM2) during menstruation. The largest number of differentially expressed genes was between Days 2 and 4 of menstruation (n = 1176). We identified several genes not previously associated with menstruation including lipopolysaccharide binding protein, serpin peptidase inhibitor, clade B (ovalbumin), member 3 (SERPINB3) and -4 (SERPINB4), interleukin-17C (IL17C), V-set domain containing T-cell activation inhibitor 1 (VTCN1), proliferating cell nuclear antigen factor (KIAA0101/PAF), trefoil factor 3 (TFF3), laminin alpha 2 (LAMA2) and serine peptidase inhibitor, Kazal type 1 (SPINK1). Genes related to inflammatory processes were up-regulated on Day 2 (early-menstruation), and those associated with endometrial repair and regeneration were up-regulated on Day 4 (late-menstruation). LIMITATIONS, REASONS FOR CAUTION: Participants presented with a variety of endometrial pathologies related to bleeding status and other menstrual characteristics. These variations may also have influenced the menstrual process. WIDER IMPLICATIONS OF THE FINDINGS: The temporal molecular profile of menstruation presented in this study identifies a number of genes not previously associated with the menstrual process. Our findings provide valuable insight into the menstrual process and may present novel targets for therapeutic intervention in cases of endometrial dysfunction. LARGE SCALE DATA: All microarray data have been deposited in the public data repository Gene Expression Omnibus (GSE86003). STUDY FUNDING AND COMPETING INTERESTS: Funding for this work was provided by a National Health and Medical Research Council of Australia (NHMRC) Project Grant APP1008553 to M.H., P.R. and J.G. M.H. is supported by an NHMRC Practitioner Fellowship. P.P. is supported by a NHMRC Early Career Fellowship. The authors have no conflict of interest to declare.

Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics.

The aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12-24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours. The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine.

Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability.

Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers.

A randomised single-blind comparison of the effectiveness of Tristel Fuse (chlorine dioxide) as an office-based fluid soak, with Cidex OPA (ortho-phthaldehyde) using an automated endoscopic reprocessor (AER) as high-level disinfection for flexible cystoscopes.

OBJECTIVE: To compare the effectiveness, safety and cost of Tristel Fuse (chlorine dioxide) with Cidex OPA (ortho-phthaldehyde; 1,2-benzenedicarboxaldehyde) in an automated endoscopic reprocessor (AER) for high-level disinfection of flexible cystoscopes. PATIENTS AND METHODS: A randomised single-blind study comparing the high-level disinfectants Tristel Fuse as a simple office-based soak and Cidex OPA using an AER was performed. Participants were 'blinded' to the agent used for disinfection of the flexible cystoscopes. All patients had negative mid-stream urine at baseline, (MSU) no symptoms suggestive of urinary tract infection (UTI) on the day of investigation, no recent antibiotic use or current indwelling urinary catheter. Patients who underwent cystoscopic biopsy during the procedure were excluded. A urine analysis was done before and 3-5 days after cystoscopy and multiple equipment cultures were performed. The Urogenital Distress Inventory (UDI-6 + two questions from the 'long-form'), symptom and quality-of-life scores were assessed before and after cystoscopy as were ease-of-use assessments and a full cost analysis. RESULTS: In all, 180 of 465 screened participants were randomised 1:1 and the mean age was 72.1 years, 17% were females and 57% of procedures were performed for bladder tumour surveillance. The urine analysis was positive in 5.4% of patients in each group and 29% (Tristel) vs 20% (Cidex) of patients had urinary leukocyturia (p = ns) after cystoscopy. The turnover (minutes per cycle) was 7.5 (Tristel) vs 26.7 (Cidex). The per-procedure costs were $11.67 (American dollars) for Tristel Fuse and $21.82 for Cidex OPA with fixed costs of $4788 for Tristel Fuse and $60,514 for Cidex OPA. CONCLUSIONS: Tristel Fuse appears to be as effective and more cost-effective than Cidex OPA for high-level disinfection of flexible cystoscopes. This has significant cost implications for the office urologist.

New Zealand's drug development industry.

The pharmaceutical industry's profitability depends on identifying and successfully developing new drug candidates while trying to contain the increasing costs of drug development. It is actively searching for new sources of innovative compounds and for mechanisms to reduce the enormous costs of developing new drug candidates. There is an opportunity for academia to further develop as a source of drug discovery. The rising levels of industry outsourcing also provide prospects for organisations that can reduce the costs of drug development. We explored the potential returns to New Zealand (NZ) from its drug discovery expertise by assuming a drug development candidate is out-licensed without clinical data and has anticipated peak global sales of $350 million. We also estimated the revenue from NZ's clinical research industry based on a standard per participant payment to study sites and the number of industry-sponsored clinical trials approved each year. Our analyses found that NZ's clinical research industry has generated increasing foreign revenue and appropriate policy support could ensure that this continues to grow. In addition the probability-based revenue from the out-licensing of a drug development candidate could be important for NZ if provided with appropriate policy and financial support.

The attenuated nine mile phase II clone 4/RSA439 strain of Coxiella burnetii is highly virulent for severe combined immunodeficient (SCID) mice.

The Nine Mile phase II clone 4 (NMIIC4) strain of Coxiella burnetii is an attenuated phase II strain that has lost the genes for virulence determinant type 1 lipopolysaccharide. These bacteria were very virulent for severe combined immunodeficient (SCID) mice. The lethal dose 50 (LD50) was ~10 bacteria. Infected SCID mice died between Day 28 and Day 53 post-infection. At termination of the experiment (Day 60) only 5 of 24 mice had survived. The degree of splenomegaly was directly related to the bacterial load in the SCID mice spleens. The NMIIC4 was avirulent in immunocompetent wild mice and bacterial DNA copies in splenic tissue were extremely low. The SCID mice that were inoculated with high doses of heat inactivated NMIIC4 C. burnetii were all alive at Day 60 and without splenomegaly. It appears that the phase I lipopolysaccharide present in virulent Nine Mile phase I but not in attenuated NMIIC4 is not the only virulence factor for C. burnetii.

Comparative sensitivity of four different cell lines for the isolation of Coxiella burnetii.

Coxiella burnetii is an obligate intracellular bacterium that causes the disease Q-fever. This is usually diagnosed by serology (immunofluorescence assay) and/or PCR detection of C. burnetii DNA. However, neither of these methods can determine the viability of the bacterium. Four different cell lines were compared for their ability to amplify very low numbers of viable C. burnetii. Two different isolates of C. burnetii were used. For the Henzerling isolate, DH82 (dog macrophage) cells were the most sensitive with an ID (50) (dose required to infect 50% of cell cultures) of 14.6 bacterial copies. For the Arandale isolate, Vero (monkey epithelial) cells were the most sensitive with an ID (50) of less than one bacterium in a 100-µL inoculum. The Vero cell line appeared highly useful as vacuoles could be seen microscopically in unstained infected cells. The findings of this study favour the use of Vero and DH82 tissue culture cell lines for isolation and growth of C. burnetii in vitro. The other cell lines, XTC-2 and L929, were less suitable.

Detecting and measuring small numbers of viable Coxiella burnetii.

Coxiella burnetii is an acidophilic, intracellular bacterium that causes the human disease Q fever. In some studies, it is important to distinguish between viable and nonviable C. burnetii. We compared four methods for detecting and measuring viable C. burnetii in biological samples as follows: growth in two different cell culture lines, infection of severe combined immunodeficient (SCID) mice (leading to death) and infection of SCID mice with detection of C. burnetii in their spleen (after euthanasia at day 50 postinfection). Two isolates of C. burnetii were used ('Henzerling' and 'Arandale'). Our in-house qPCR assay for C. burnetii DNA was used as a control. SCID mouse inoculation was more sensitive than cell culture. The assay that detected C. burnetii in SCID mouse spleens was slightly more sensitive than SCID mice deaths alone. Approximately one viable C. burnetii cell could be detected by this method, making it suitable for determining the viability of C. burnetii in a sample.

New Zealand's drug development industry--strengths and opportunities.

AIM: Globally the traditional model of drug development is changing and the large pharmaceutical companies are looking externally for innovative compounds, new technologies and cost-effective drug development services. New Zealand (NZ) can capitalise on its expertise in innovative drug discovery and development but needs to be able to define and promote its capabilities to the global drug development industry. An approach that will enable a ready assessment of NZ's expertise is presented. METHOD: Interviews will be carried out with key senior personnel from NZ drug discovery groups, drug development companies and organisations that provide a wide range of research and development services. The resulting data will be collated to document current capabilities and expertise, as well as limitations, in NZ's industry and assess their potential for the future. Participants will be asked to identify factors that support and factors that limit their organisation's progress in drug development and to suggest policies that could be implemented to positively influence future performance. CONCLUSION: A formal assessment of New Zealand's capabilities, strengths and limitations in drug development will aid in the promotion of its expertise to overseas organisations and enhance the economic benefits that could accrue to New Zealand.

A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease.

Multiple lines of evidence point to mitochondrial oxidative stress as a potential pathogenic cause for Parkinson's disease (PD). MitoQ is a powerful mitochondrial antioxidant. It is absorbed orally and concentrates within mitochondria where it has been shown to protect against oxidative damage. We enrolled 128 newly diagnosed untreated patients with PD in a double-blind study of two doses of MitoQ compared with placebo to explore the hypothesis that, over 12 months, MitoQ would slow the progression of PD as measured by clinical scores, particularly the Unified Parkinson Disease Rating Scale. We showed no difference between MitoQ and placebo on any measure of PD progression. MitoQ does not slow the progression of PD, and this finding should be taken into account when considering the oxidative stress hypothesis for the pathogenesis of PD.

The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients.

BACKGROUND: Increased oxidative stress and subsequent mitochondrial damage are important pathways for liver damage in chronic hepatitis C virus (HCV) infection; consequently, therapies that decrease mitochondrial oxidative damage may improve outcome. The mitochondria-targeted anti-oxidant mitoquinone combines a potent anti-oxidant with a lipophilic cation that causes it to accumulate several-hundred fold within mitochondria in vivo. AIMS: In this phase II study, we investigated the effect of oral mitoquinone on serum aminotransferases and HCV RNA levels in HCV-infected patients. METHODS: Thirty HCV patients who were either non-responders or unsuitable candidates for standard-of-care (pegylated interferon plus ribavirin) were randomized to receive mitoquinone (40 or 80 mg) or placebo once daily for 28 days, and serum aminotransferases and HCV RNA levels were measured. RESULTS: Both treatment groups showed significant decreases in absolute and percentage changes in serum alanine transaminase (ALT) from baseline to treatment day 28 (P<0.05). There was also a significant difference between incremental area under the curve for ALT between baseline and day 28 for the 40 mg treatment group against placebo (P<0.05). The differences in plasma ALT activity from baseline to day 28 in both mitoquinone groups compared with placebo did not reach significance (P>0.05). There was no change in HCV load on mitoquinone treatment. CONCLUSIONS: Administration of the mitochondria-targeted anti-oxidant mitoquinone significantly decreased plasma ALT and aspartate aminotransferase in patients with chronic HCV infection, and this suggests that mitoquinone may decrease necroinflammation in the liver in these patients. As mitochondrial oxidative damage contributes to many other chronic liver diseases, such as steatohepatitis, further studies using mitochondria-targeted anti-oxidants in HCV and other liver diseases are warranted.

Evaluation of policies to support drug development in New Zealand.

OBJECTIVES: Changes in the traditional model of drug development are creating a potential opportunity for New Zealand's drug development industry. This research evaluates whether New Zealand could utilise some of the policies employed by countries with successful drug development industries. METHODS: A framework to support a drug development industry was developed by taking into account policies that affect the industry. The framework was then used to analyse the types of policies provided by different countries and to postulate six different models that support a pharmaceutical industry. RESULTS: Countries with a successful drug development industry have identified their strengths, analysed the opportunities in the industry, and have employed consistent and specific policies in support of their industry. New Zealand's policy in support of its drug development industry is most similar to that of the medical research-based model of the UK, Australia and Canada. CONCLUSIONS: New Zealand needs to develop a consistent policy for support of its drug development industry based on identifying and focussing on the competencies where it is internationally competitive. A strong partnership with Australia could capitalise on the strengths of both countries and linkages with other Asia-Pacific countries could further promote the region's capabilities in drug development research.