'...what's the problem here, rejected 6 times?'

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MSAC rejected a new breast cancer diagnostic after receiving a late submission from a competitor - through a former committee member - that it did not disclose to the applicant. It also delayed the release of the Public Summary Document while it worked on evidence to support the rejection.

This is an edited version of an article published in BioPharmaDispatch.

Imagine the following scenario - because it happened

A company makes a submission to one of the federal government's key advisory committees seeking funding for a new medical technology in the form of a diagnostic genetic test. 

It is the company's sixth submission but all indications are good with an economic sub-committee providing a largely positive review.

Just three days before the meeting at which the submission will be considered, the company is contacted by officials on behalf of the committee and asked to provide a clinical study report from a key trial.

The company does not have the report because it did not conduct the trial. However, it provides the contact details of its lead investigator.

Yet what the company does not know is that the request for the clinical study report was triggered by a late submission from a competitor.

The competitor disclosed their obvious conflict but their submission was still accepted. The applicant was not informed or even given an opportunity to respond to the substance of the competitor's submission - this is after the formal evaluation of the applicant's submission.

In an additional twist, the competitor's submission was made by an ex-member of the advisory committee and they may have even been involved in at least one of its previous decisions to reject the applicant's technology.

The applicant's submission was rejected but it did not end there.

The relevant Public Summary Document took almost six months to finalise and it was only provided to the applicant after it submitted a Freedom of Information (FOI) request.

The documents released under FOI appear to reveal the delay may have been because the advisory committee and its supporting officials were building a body of evidence - post the formal decision - in support of their decision to reject the applicant's technology.

Specialised Therapeutics Australia's OncotypeDX test

OncotypeDX is a tumour profiling test that analyses 21 genes within a tumour sample. The test can help predict the risk that a woman’s breast cancer may recur and the likely benefit chemotherapy may have in reducing that risk.

Results from the TAILORx clinical trial showed women diagnosed with hormone receptor-positive, HER2-negative, node-negative early breast cancer may be able to avoid chemotherapy if they undergo the OncotypeDX test and receive a mid-range recurrence score.

The Medical Services Advisory Committee

The Committee has rejected the test six times, most recently in August last year. This followed previous rejections at its meetings held in July 2013, April 2014, November 2015, July 2016 and July 2017.

The most recent rejection came despite a largely positive review by MSAC's economic sub-committee (ESC). The ESC considered the OncotypeDX application at its meeting on 13 June 2019.

The ESC highlighted the funding of the test in comparable countries like Canada, the UK and US, and it even said the submission may have underestimated the cost-offsets associated with its use.

“ESC noted that there is an increasing view that clinicians should be using a higher level of evidence based on genomic subtyping of individual cancers (in addition to traditional histological features and immunohistochemical markers) to provide more specific and tailored treatments for breast cancer patients. Oncotype DX and other similar multigene assays are being increasingly used worldwide, and there is an increasing clinician-led demand for access to these types of assays,” it said.

It added, ”From the consumer point of view, ESC noted that genomics is becoming a part of better patient-centred care. There is considerable positive benefit for patients of better diagnoses leading to better treatment decisions, including patients being able to avoid chemotherapy if it is not required. ESC noted that equity of access issues arise from this test not being rendered in Australia.”

The lead up to MSAC's August 2019 meeting

MSAC met on 1 and 2 August with OncotypeDX scheduled for the first day.

The documents released through FOI have revealed significant activity and discussions in the days immediately before the meeting.

The names of MSAC members have been redacted in the FOI documents. Specialised Therapeutics Australia has appealed this decision, and others in relation to the FOI, to the Office of the Australian Information Commissioner.

According to the documents, the Department of Health's MSAC secretariat received an email via its 'HTA inbox' at 10.48 am on Friday 26 July 2019 - MSAC was scheduled to consider OncotypeDX the following Thursday (1 August).

The email was sent by Professor Graeme Suthers. Professor Suthers is the director of genetics at Sonic Pathology Australia and he is also a former member of MSAC.

He was on the committee from 2009 until 2017 during which time it considered and rejected the OncotypeDX test on multiple occasions.

Professor Suthers joined Sonic in 2014 but remained a member of MSAC. He is an esteemed expert on genetic pathology but remaining on MSAC presented significant challenges - having a senior executive from Sonic on MSAC might be considered broadly the equivalent of having a current senior pharmaceutical industry executive on the Pharmaceutical Benefits Advisory Committee.

In response to questions, Professor Suthers confirmed he removed himself from involvement in decisions regarding the OncotypeDX test following his appointment to Sonic.

In the 26 July email to the Department of Health's 'HTA inbox', Professor Suthers clearly disclosed a conflict (Sonic is a competitor).

He said, “The brief Agenda that was circulated by email notes that ‘Feedback and comments are welcome at any stage during the MSAC process’. I recognise that the preparatory meetings and evaluations have been completed, but I will take you at your word and provide a brief comment. In doing so, I declare an interest (Sonic has been evaluating competing methods for estimating prognosis and predicting chemo‐responsiveness for 5 years) and a conflict (we have chosen to provide a different gene expression assay)."

Professor Suthers submitted information questioning the value of the OncotypeDX test.

Officials from the MSAC secretariat quickly advised committee members of the late submission and confirmed it would be added as 'Consultation Feedback'.

The documents do not reveal any discussion or consideration of whether it would be appropriate to accept the late submission.

They also do not reveal any discussion on whether to communicate the submission's existence to Specialised Therapeutics Australia, let alone provide the company with an opportunity to respond - at that stage, the formal pre-MSAC evaluation process was complete.

A committee member responded to the MSAC secretariat's communication by asking that it obtain a copy of the TAILORx clinical study report.

On Monday 29 July, three days before the MSAC meeting, the secretariat contacted the company through a representative to ask for a copy of the clinical study report - it did not say why and it did not reveal the request was in response to a late submission from a competitor.

The representative responded within minutes saying they did not have access to the report. They undertook to work to identify sources of relevant additional information.

On Tuesday 30 July, an email exchange between members of MSAC and its secretariat included a discussion on one of the papers (New England Journal of Medicine) referred to in Professor Suther's late submission.

Arguably, this email exchange with reference to the paper establishes a connection between the late submission and the subsequent MSAC consideration of OncotypeDX.

There is also a text message exchange between what appears to be a Department of Health official and member of MSAC. We know the text message is related to OncotypeDX because it has been included in the FOI.

Yet it simply says, "Sorry but are you free for a final chat about...", with the subject for discussion redacted under Section 47C of the FOI Act - meaning it is 'deliberative' to the outcome.

Also on 30 July, the company's representative confirmed to the MSAC secretariat it did not have access to and therefore could not provide the clinical study report. Yet it did provide contact details for Dr Joseph Sparano - the clinician who led the TAILORx study.

It is unclear if MSAC or its secretariat contacted Dr Sparano (The publisher has asked the Department of Health if and when Dr Sparano was contacted).

The MSAC secretariat did not reveal the late submission to Specialised Therapeutics Australia, let alone that it was from a competitor. The company only learnt of the late submission through the FOI.

What happens after the meeting?

What follows the rejection is a long process of drafting and re-drafting the Public Summary Document (PSD).

The company did not receive the ratified PSD until 29 January 2020 - six months after the outcome - and after it submitted an FOI request on 24 January.

The documents obtained under FOI reveal the first draft of the PSD was emailed to MSAC members on 26 August - just four weeks after the meeting.

What followed was months of email discussions over the PSD - the substance of which has been almost entirely redacted from the relevant emails. The Department of Health has also redacted the iterative versions of the PSD.

Section 47C of the FOI Act is used as the main reason for redacting the content of the discussions regarding the OncotypeDX PSD - this means they are considered 'deliberative' to decision-making.

How can MSAC be having deliberative discussions about the OncotypeDX after its meeting? Some of these 'deliberative' email discussions take place in October and November - three to four months after the rejection.

The implication is that the evidentiary basis for the decision in August 2019 - a rejection that could have been influenced by an undisclosed submission from a competitor - may have been partly or significantly generated after the rejection.

One email that might say it all

The documents released under FOI include one telling email - sent by Department of Health First Assistant Secretary Adriana Platona PSM at 2.38am on 4 September - around five weeks after the rejection. 

The name of the recipient is redacted but the reference to Section 47F of the FOI Act suggests it is a member of MSAC.

In the email, Ms Platona simply says, "...what's the problem here, rejected 6 times?"

It is a standalone email - it is not in response to anything and there is no reply - yet it seems to say so much.