Decision to decline inactive medicines funding applications

Cardiovascular System

Eplerenone - Heart failure: ejection fraction <=40%, and diabetes or a risk of diabetes

A question was raised as to whether the adverse effect of gynaecomastia in relation to the use of the currently funded treatment for heart failure (spironolactone) had been addressed as part of the clinical advice process.

We note that gynaecomastia as a side effect of spironolactone treatment has been discussed by both PTAC and the Cardiovascular Subcommittee of PTAC during the following meetings:

PTAC – 5 & 6 November 2015 (see item 9) – direct link to meeting record can be found here [PDF, 1.4 MB].

Cardiovascular Subcommittee – 17 February 2016 (see item 1) – direct link to meeting record can be found here. [PDF, 141 KB]

PTAC – 11 & 12 August 2016 (see item 1 – Subcommittee Minutes) – direct link to meeting record can be found here. [PDF, 348 KB]

PTAC – 4 & 5 May 2017 (see Eplerenone – 2.13 – 2.16) – direct link to meeting record can be found here. [PDF, 534 KB]

Cardiovascular Subcommittee - 8 May 2019 – (see item 6, 6.5 – 6.8) – direct link to meeting record can be found here [PDF, 803 KB].

We also note that eplerenone is funded for those people who meet the Special Authority criteria: heart failure with ejection fraction less than 40% and who are intolerant, or have had a clinically significant adverse effect while on optimal dosing of spironolactone(external link).

The decline of this application does not impact on the ability of patients who have had an adverse reaction on spironolactone to access eplerenone via Special Authority.

Ivabradine for chronic heart failure

There is no  new published evidence that supports the use of ivabradine in the treatment of chronic heart failure. However, ivabradine should be funded for the treatment of inappropriate sinus tachycardia (IST)

The decision to decline the application for the use of ivabradine to treat chronic heart failure does not impact  the assessment of the application for the use of ivabradine for the treatment of inappropriate sinus tachycardia (IST).

The funding application for ivabradine for the treatment of IST remains open(external link).

Our latest clinical advice received from the Cardiovascular Subcommittee recommends that Pharmac continue to investigate options to fund ivabradine even if the product was unregistered.

The record of this meeting can be found here [PDF, 803 KB].

Dermatology

Sodium hypochlorite, 5% diluted - Eczema in cases with secondary bacterial infection

No consultation feedback was received.

We have subsequently considered that the advice we received to decline the application was based on an assumption that simple bleach could be bought for a lower price than the co-payment ($5.00). However, we consider that this treatment would most likely be used in children and that there is no prescription co-payment on medicines for children aged 13 and under. Should a family be required to purchase bleach to use as a treatment, this would incur a charge, whereby a prescription for sodium hypochlorite 5% diluted would not. Therefore, we are now reconsidering this application and intend to seek further advice on this application.

Clindamycin phosphate, topical - Acne

Topical clindamycin is an evidence-based treatment for a number of vaginal conditions where there are currently no other optimal treatments available.

There is an active application for funding of clindamycin vaginal cream that remains under consideration.(external link)

This application for clindamycin vaginal cream will not be affected by this decline.

Hormone Preparations - Systemic Excluding Contraceptive Hormones

Whole Thyroid Extract, Normal Release T3 and Extended Release T3. - Hypothyroidism

Additional evidence was provided in support of this application.

We intend to seek further clinical advice following the submission of additional evidence.

Infections - Agents for Systemic Use

D-mannose - Uncomplicated cystitis during pregnancy or associated with neurogenic bladder

Information was provided indicating that additional evidence to support this application was imminent.

We intend to seek further clinical advice following the submission of additional evidence.

Posaconazole - Prophylaxis of fungal infection in patients with aplastic anaemia

Additional clinical information relating to this application was submitted.

We intend to seek further clinical advice following the submission of this information.

Posaconazole - Prophylaxis of fungal infection in patients with acute lymphoblastic leukemia

Additional clinical information relating to this application was submitted.

We intend to seek further clinical advice following the submission of this information.

Nervous System

Buprenorphine patches - Pain - persistent moderate/severe

Information was provided indicating that additional evidence to support this application was imminent.

We intend to seek further clinical advice following the submission of additional evidence.

Capsaicin 0.075% cream - Cannabinoid hyperemesis syndrome

Additional evidence was provided in support of this application.

We intend to seek further clinical advice following the submission of additional evidence.

Lidocaine [Lignocaine] With Prilocaine cream - Removal of Special Authority

Lidocaine [Lignocaine] With Prilocaine cream - Pain – Community listing

The funded comparator, as indicated in the records, is not currently fully funded in the community. In addition, lidocaine with prilocaine cream is noted in the NZ Contraception Guidelines as an option for use in IUC insertion.

We will initiate a new funding application for lidocaine with prilocaine cream for IUD insertion as we consider the best way to progress consideration for lidocaine with prilocaine cream for IUD insertion is to consider funding for it as a specific indication.

Micronutrient formulas - ADHD and/or mood dysregulation

We received feedback in support of declining this funding application

We note the response supporting the decline of this funding application.

Modafinil - Mood disorders, psychoses, attention deficit disorders, drug dependency and shift workers

Modafinil is reported to be life changing for some consumers and it would be useful if it were funded.

We acknowledge that some consumers may be currently self-funding modafinil. No additional evidence or information has been provided to support the application at this time. We would be happy to reconsider this application should further published evidence be provided.

Naltrexone hydrochloride - Removal of Special Authority

There is an unmet health need for people with alcohol use disorder (AUD) and there is potential benefit that naltrexone could have for these people. Could the Special Authority be amended to allow any prescriber type to prescribe naloxone to increase accessibility?

We note the request and the clinical opinion and associated references to support this request. We will seek further clinical advice on the prescriber type for naltrexone.

Oncology Agents and Immunosuppressants

Bevacizumab - Ovarian cancer, advanced

Further information indicating there is updated clinical trial evidence regarding the health benefits that could be achieved from bevacizumab treatment compared to currently available treatments was provided. In addition, cost-effectiveness was a factor in the previous recommendation for decline and, with the increased availability of biosimilars, the cost-effectiveness of bevacizumab may have improved.

We note the availability of updated evidence. We have decided not to progress the application for bevacizumab for advanced ovarian cancer to a decline decision at this time, pending further clinical advice.

Bevacizumab - Relapsed, recurrent glioblastoma multiforme

Further information indicating updated Phase III evidence and real-world evidence has been made available since the last clinical review of bevacizumab for relapsed, recurrent glioblastoma multiforme. This feedback considered access to bevacizumab for this patient group would result in health benefit for many patients. 

We note the availability of updated evidence. We have decided not to progress the application for bevacizumab for elapsed, recurrent glioblastoma multiforme to a decline decision at this time, pending further clinical advice.

Fulvestrant - Breast cancer - locally advanced or metastatic breast cancer (1st line treatment)

Fulvestrant is indicated for use in patients not previously treated with endocrine therapy, as well as in the second-line for patients previously treated with endocrine therapy. It was noted that the application was for first-line treatment of fulvestrant with evidence of benefit supported by the FIRST and FALCON clinical trials assessing fulvestrant in the first line against anastrozole treatment. This evidence indicates clinical benefit for patients including improvement in the duration of progression free survival of fulvestrant compared to anastrozole and an earlier trial (2012) indicating the addition of fulvestrant to anastrozole was associated with increased long term survival compared to anastrozole alone.

We note that the clinical advice received from the Cancer Treatments Subcommittee of PTAC (CaTSoP) [PDF, 692 KB] was that the patients most likely to benefit from treatment with fulvestrant are postmenopausal women with ER positive advanced breast cancer who have received a good response to prior aromatase inhibitor treatment, with use of fulvestrant in the second line.

CaTSoP considered at the time that there was a lack of data regarding the optimal sequencing and cost-differential between fulvestrant and aromatase inhibitors and therefore considered it would not be appropriate to list fulvestrant in the first line setting.

CaTSoP reviewed both the studies as part of its assessment.

• FIRST(external link); and
• FALCON(external link)

At this stage, as no new evidence has been provided to indicate superiority of fulvestrant in the first-line compared to second-line treatment, this application has proceeded for decline; however, we would be happy to reopen the application if evidence of benefit of fulvestrant in the first line compared to second line can be provided.

Lapatinib ditosylate - Breast cancer - Second line metastatic HER2 positive breast cancer

No concerns were noted by respondents on the proposal to decline lapatinib, indicating that there is an alternative treatment option available for these patients. Requests for funding new generation tyrosine kinase inhibitors neratinib and tucatinib for this patient group as a second line treatment.

We appreciate the feedback regarding the decline of lapatinib, and available alternative treatment options for this patient group. We have not previously received or assessed any applications for neratinib and/or tucatinib and would be pleased to consider a funding application for the use of neratinib and/or tucatinib in this setting. 

Pertuzumab - Breast cancer, HER2-positive, locally advanced, inflammatory or early-stage, neoadjuvant treatment

Further information indicating there is updated clinical trial evidence regarding the health benefits that could be achieved from pertuzumab treatment in this patient group was submitted.

We note the availability of updated evidence. We have decided not to progress the application for pertuzumab to a decline decision at this time, pending further clinical advice.

Rituximab - Chronic lymphocytic leukaemia, 17p del

A request for clarification was received on what the effect of declining this application for rituximab in patients with chromosome 17p deletion chronic lymphocytic leukaemia (CLL) would be on the current Special Authorities for rituximab and for venetoclax

We note that the decline of the application for rituximab for patients with chromosome 17p deletion CLL does not have any effect on the current Special Authority criteria for rituximab or venetoclax.

Patients with newly diagnosed CLL with 17p deletion will continue to be ineligible for funded rituximab. Venetoclax is not funded in combination with rituximab for patients with newly diagnosed CLL with 17p deletion.

However, for patients with relapsed/refractory CLL, venetoclax is funded, and will continue to be funded, in combination with rituximab, regardless of cytogenetics.

Special Foods

Extensively hydrolysed formula - Alfare - Cow's milk protein allergy, food intolerance and hypersensitivity

Nestle Health Science, the supplier of Alfare, has indicated that they wish to continue to have the application for funding of this product assessed.

We proposed to decline the funding application for Alfare as we understood the supplier no longer wished to pursue it. However, we note the feedback from the supplier that they wish to continue to progress this application for funding.  We have decided not to progress the application for extensively hydrolysed formula - Alfare for cow's milk protein allergy, food intolerance and hypersensitivity to a decline decision at this time and will engage further with the supplier on this application.

Various

Fomepizole - Methanol poisoning

We have received feedback from clinical stakeholders and the supplier of fomepizole, who considered that the funding application should remain open to be considered for funding due to the benefits above current treatment, the development of NZ antidote guidelines, and the inclusion of fomepizole on the WHO essential medicines list.

We note the clinical opinions of additional benefit of fomepizole over currently funded options. We have decided not to progress the application for fomepizole for methanol poisoning to a decline decision at this time.

Many of the applications that we consulted on have been inactive for a number of years. It questioned how this process to progress applications to a decision makes decision making ‘clearer, faster and simpler’. 

A number of other suggestions were provided to improve decision making and transparency more generally including:

Publication of the health economic assessments for applications on the Options for Investment and Cost Neutral/Cost Saving lists:

• Set defined timelines for funding decisions and the stages involved in processing applications.
• Reinstate a public list of medicines declined for funding by the PHARMAC Board and report the number of applications received, listed, and declined
• Making it a priority to complete funding decisions for applications on considered to be options for investments.

This approach of declining applications that are not active is fairly new, with our first tranche of declines being progressed in 2019. Prior to this, Pharmac did not generally progress applications to a decline decision, and they became inactive. We are still working through the backlog of inactive applications. Therefore, a significant number of applications included in this consultation had been inactive for some time before the release of the consultation. We consider that, in making a decision about declining an application, we are making it clear about our intentions when it comes to that application. In providing this certainty, we consider that this simplifies our process and makes it easier to understand.

The suggestions made in the consultation feedback on how to further improve decision making has been provided to relevant Pharmac staff involved in reviewing the decision-making process. These staff members will consider this feedback as part of their work.

In a number of cases, applications have become inactive as further evidence that would be required to support the application had not been provided. Suggestions that a review take place at Specialist Advisory Committees on inactive applications to see if new evidence had come to light for inactive applications.

Questions were raised as to why there is a large amount of variation between applications in how long they have been inactive before they have been progressed for decline, and  what would be required to resubmit an application after it had been declined.  Questions were raised on the use of PTAC and Specialist Advisory Committee recommendations to justify the progression to decline, noting a particular instance when new evidence came to light after the Specialist Advisory Committee had made a recommendation.

We the use of Specialist Advisory Committee for review of inactive proposals has been forwarded onto the Medical Directorate for its consideration.

The variation between applications on how long they have been inactive before they were progressed for decline is as a result of this being a relatively new approach. We are in the process of clearing the ‘backlog’, hence the variation.

An application may be resubmitted once it has been declined, but the rational as to why the initial application was declined would need to be addressed in the resubmission.

Pharmac uses clinical experts in the form of PTAC and Specialist Advisory Committees to provide it with advice on applications. Should new evidence come to light after our experts have made a recommendation, we would be happy to consider whether further advice should be sought.