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Consumer access to pharmaceutical benefits

CHAIR —I welcome the next panel members. Do you have any comments to make on the capacity in which you appear?

Dr Major —I am here in my own capacity. I am the Director of Rheumatology in the Newcastle Bone and Joint Institute. As such, I have an ongoing interest in bones, osteoporosis and associated problems with fracture.

Prof. Oakley —I am a consultant rheumatologist, also from the Newcastle Bone and Joint Institute at the Royal Newcastle Centre. I have a conjoint appointment at the University of Newcastle. I am also here in my own capacity. As a rheumatologist I have an interest in the treatment of osteoporosis. I am also interested in research on osteoporosis.

Dr Inderjeeth —I am presenting in my capacity as a clinical academic at the University of Western Australia and as a representative of the Australian and New Zealand Society for Geriatric Medicine.

CHAIR —I understand you have all been given information on parliamentary privilege and the protection of witnesses.

Dr Inderjeeth —Yes, I have, thank you.

CHAIR —We have received submissions from you. I would like to invite each of you to make a short opening statement and then we will ask you some questions. We will start with Dr Major.

Dr Major —Perhaps I should explain briefly as to why I am here. I have an interest in and concern about elderly people breaking their bones, with the consequence that they become severely disabled. This is a national epidemic. We have, in New South Wales at least, almost $12 million a year being spent on people coming back with recurrent fractures. These are people who have already sustained a fracture and have a further fracture that requires hospital admission. There is an enormous gap between people receiving treatment and people who should be on treatment and are not receiving it. Only one in 10 of these people who should be on treatment is receiving it. There is a treatment failure. The first hurdle, in a sense, is that we have this issue.

The second hurdle is that we should be able to give the most effective treatment. It is clear that there are treatments that can reduce the refracture rate by 60 per cent. One of the paradoxes we have encountered recently is that some of these people who will benefit from the treatment will, later on, run into complications of the treatment. Our concern is that this may be influenced by the choice of drug that we are using. We have some evidence that is strongly pointing in that direction and it concerns me that, if this ruling of equivalence is brought in, we may lock ourselves into a position that will be difficult to retreat from. My concern is on those grounds. I am also concerned that we should be treating these people as early as possible to make sure that we can intervene and stop the fracture cascade.

Prof. Oakley —One of the great challenges of the 21st century in Australian society will be managing the increasing burden of diseases of ageing, of which osteoporosis is one. Prior to the 1990s, we relied primarily upon calcium supplements, vitamin D and, in the case of post-menopausal osteoporosis, which is probably the largest group, we used oestrogen. Oestrogen is only useful for that group and it subsequently came under a cloud by association with breast cancer.

In the 1990s we saw the introduction of a highly efficacious class of drugs called the bisphosphonates, following large randomised controlled trials showing around 60 per cent reduction in fracture risk. We first saw alendronate, marketed as Fosamax by Merck Sharp & Dohme, and then risedronate, marketed by Sanofi-aventis as Actonel. It is important to note that in all these trials patients received calcium and vitamin D supplements. These supplements are essential for the efficacy of these drugs.

The introduction of bisphosphonates completely changed the treatment of osteoporosis. The patent for alendronate has now expired and we have seen the emergence on the market of less expensive generic brands. Risedronate remains under patent for a few more years and comes in combination packs with calcium and vitamin D, and the government is now seeking to reduce the cost of osteoporosis treatment by making these interchangeable. While I understand and support such endeavours, I would worry that these decisions are premature and the implications have not been fully evaluated.

I believe this is so for a number of reasons. The two drugs are not the same and differ in terms of chemistry and plasma half-life and, while bioequivalence between alendronate and risedronate has been demonstrated in terms of bioavailability and the clinical trials suggest that the two drugs have similar clinical efficacy, the key difference is in the end product, which comes with the supplementation of calcium and vitamin D. Currently, generics do not come with vitamin D or calcium and the doctor must remember to prescribe the supplement. The patients must then purchase vitamin D and calcium, which is not on the PBS, and then they must remember to take it, and we know that in real life compliance may vary and maybe only between 50 and 60 per cent. These factors—the additional costs and having to remember to take these medications—may further reduce compliance and efficacy considerably. We simply do not know.

The other concern that I have is one that Dr Major has already talked about—the emergence of these new atypical minimal trauma fractures of the shaft of the femur, or the thigh. The case reports have been emerging since 2005 and at present are almost exclusively linked to alendronate. There is fierce debate in the medical literature as to whether the phenomenon is real. There is also debate as to whether this is a class effect and seen with all bisphosphonates, or whether it is specific to alendronate. I really think that we need a number of years—perhaps five more years—to really work this out and we are going to require ongoing large epidemiological and laboratory studies for this issue to be resolved. On the basis of these points, I think that we should really defer any such judgements regarding the PBS and subsidy for these medications. Thank you.

CHAIR —Thank you. Dr Inderjeeth.

Dr Inderjeeth —Thank you. I am presenting this submission in my capacity as a clinical academic and a representative of the Australian and New Zealand Society for Geriatric Medicine and I wish to comment on the proposal by the PBAC to create new therapeutic groups. Our understanding is that initially this will apply to bisphosphonates, and unfortunately it is possible that this may be rolled out to involve other therapeutic groups as well, which may have similar, if not worse, impacts on the treatment of other conditions.

We have a number of concerns to raise with regard to the potential adverse impact on patient treatment especially on older patients. We know already that the diagnosis of the condition is quite low. We know that patient and clinician awareness of the need to treat the condition is quite low. We know that when patients are treated about 40 or 50 per cent of them are likely to stop treatment within one to two years. Adding additional levels of complexity to treatment of existing choice may have an adverse impact on treatment of the condition that is quite important in terms of reducing morbidity and mortality and, more importantly, cost to health-payers.

The treatment choice is generally made by clinicians based on patient and clinician preference and is usually guided by cost, the risk-benefit ratio, and convenience, and this option will be taken away from clinicians. Clinicians also consider the special qualities of a particular agent in terms of the evidence of benefit in a particular subgroup of patients or patients with comorbidity and the potential interactions with other medications and diseases. The patients we deal with are generally the frailer, older group with multifactorial problems, with multiple medical issues and comorbidity, and polypharmacy, which is multiple medications they require for multiple medical conditions. In our belief, reducing the choice of the treatment of patients with a high-risk profile is fraught with risk.

Our concerns relate to the removal of the choice of the clinician and the patient to make a judgement on what would be the most appropriate agent for their particular disease profile, and this may impact on compliance. Notwithstanding the pharmacological differences of these agents, geriatricians would prefer to select agents based on good available evidence, efficacy and the onset effect and tolerability in the older patient groups. We tend to match the best profile of an agent with the requirement for the patient in terms of how soon we want it to work and what side effects and interactions there are with other treatments.

Current treatment selection for osteoporosis therapy is based on patient profile and factors that influence choice of dosage, frequency and modality of delivery. This might be impacted on by the new ruling. Currently, not all therapeutic groups are available across the range of dosages, frequencies and modalities of delivery and allowing interchangeability may impact adversely on this choice, which is made for specific indications. For example, the choice of less frequent dosing, such as monthly over weekly, is based on the premise that compliance, cost and convenience may be improved, and removing this option may adversely affect patient outcomes through reduced compliance and convenience and through the cost of formal or informal carers—that is, less frequent dosing may be preferred for patients who require supervision. A significant proportion of older patients have cognitive impairment or dementia syndromes and require a carer to supervise their treatment. Hence, there may be advantages in less frequent dosing as these treatments require specific observation after treatment to ensure patients are not at risk of side effects from poor compliance.

Secondly, not all agents are available with complementary calcium and vitamin D, which you have already heard about. This is supplied by some but not all pharmaceutical brands. This is fundamental as the benefit of these agents has been demonstrated only in situations where calcium and vitamin D are optimised as well. Furthermore, these supplements are provided with combinations of calcium or vitamin D in dosages and combinations that vary widely. We tend to match combinations based on whether the patient also requires additional vitamin D, calcium or a combination. With the lack of standardisation across each of these pharmaceutical agents and their co-supply of calcium and vitamin D combinations there is potential for confusion, resulting in either diminished benefit or increased risk of incorrect combinations, causing overdosing and toxicity from incorrect or excessive supplementation. This is a real risk, especially in patients who are taking multiple medications for multiple medical conditions. We already have difficulty with poor compliance as well as excessive intake of medications, interactions and side effects.

Similar arguments may apply to other therapeutic groups, should the PBS choose to extend this to other therapeutic groups, including the treatment of conditions like cardiovascular disease, including hypertension, heart failure and diabetes. This is a major concern for us as well. We agree with statements made by prominent professional societies involved in osteoporosis, such as the Australian & New Zealand Bone & Mineral Society, and support the points as outlined in their submissions to you.

To summarise the view of our society, the new proposal is likely to disadvantage all patient groups but more so the older patient groups and may lead to poorer compliance and adverse outcomes, including fracture and toxicity. I think we need to prevent this type of legislation going through because it will have a negative impact when we are trying to treat the very conditions that we are trying to manage better and prevent, because currently we probably do not optimally manage these conditions.

CHAIR —Thank you.

Senator RYAN —Any of you should feel free to answer these questions because I have taken note of your verbal submissions and looked at your written ones. I gather that you have two concerns: one is the assumed interchangeability between the two bisphosphonates in this new group, but you also have concerns about patient interchangeability between brands within the genericised molecule. Is that a fair characterisation of your submission?

Dr Inderjeeth —Yes, it would be my assumption as well.

Prof. Oakley —Did you mean the femoral fractures when you were talking about toxicity? We are concerned about that particularly at Newcastle.

Senator RYAN —Could you explain that further? I was just referring to the fact that your submissions indicate that you are not just concerned with the grouping of—and I am not going to try to pronounce their names—distilled patented bisphosphonate—

Prof. Oakley —You are correct. I understand what you mean.

Dr Major —Our concern is primarily about the emerging possibility that the two bisphosphonates have different safety profiles and, in particular, they are known to have slightly different modes of action, so the extent to which they leach onto bone varies. Alendronate, for instance—Fosamax—is attached firmly to the bone for a long period of time, whereas risedronate is able to come off the target within six months or so, so there is a greater degree of reversibility.

We are seeing that both drugs are highly effective in preventing fractures, particularly hip fractures, which is one of the most devastating outcomes. But it seems there is a paradox. We are seeing fractures down the shaft of the thigh bone and this is an uncommon thing. The overall treatment is still worthwhile, but we are now starting to see this complication arise. It seems likely that this complication is preferentially linked to the longer-acting variety of bisphosphonate—the one that is harder to get off the bone. As Dr Oakley was referring to, there is a raging issue about it. Indeed, it is labelled as the hot topic in the American College of Rheumatology current releases as to whether this particular fracture risk is going to be a big problem for us or not.

People are walking along, they develop a bit of thigh pain and then all of a sudden the thigh just snaps straight through. It is a particular kind of fracture and, interestingly, one of the first case reports of this was in American by a doctor who had gone onto treatment in her 50s and continued as the treatment seemed to be going very well. Then she snapped one thigh riding on the subway and shortly after did the other thigh. It is a devastating event that is fortunately rare. We need to make sure that we understand more about it and that we are not locked into a situation where we have no choice but to use perhaps the less favourable drug. Time will tell. At the moment, I do not think we can claim this with certainty, but there are very strong indications for it.

Senator RYAN —So from a clinicians point of view—I would ask all three of you to comment on this if you could—do you consider these two separate molecules to be as interchangeable as just switching any other medicine? Would you want to switch a patient between them on one occasion or multiple occasions based on considerations such as price or the cost to the patient? Do you think these drugs should be considered perfectly interchangeable for patients?

Dr Major —I do not think they are interchangeable like that.

Prof. Oakley —I agree, although, as Dr Major says, time will tell whether these differences are significant.

Dr Inderjeeth —We tend to base decisions on treatment on the available evidence. Whilst it is difficult to compare different agents in situations where they are not directly compared to each other in a single trial, we base decisions on the outcomes and the efficacy of these agents. Firstly, we are fully aware that, for example, alendronate or Fosamax is a more potent bisphosphonate in reducing bone turnover. That may be desirable in some patients but not in others. Secondly, in terms of the bone density effect, there is a differential between the two. Thirdly, in terms of what we think is the onset of fracture effect, there may be some differences. For example, in older patients you may want to choose a less potent bisphosphonate that has an earlier onset of action compared to one that is more potent and has longer term effects.

You will need to balance the efficacy in terms of reducing the fracture risk against the risk of potential toxicity from oversuppression of what we call bone turnover because these agents tend to reduce the rate at which bone is broken down. Older people and younger people are different so we tend to make different choices depending on the age and other co-morbidities in a particular patient. That is a choice that will be taken away from us if there is interchangeability. The short answer is that we perceive—and I am a clinician, not a basic scientist—that there is a difference in how potent and how effective these agents are in reducing what we call bone turnover as well as the risk of fractures and the timing based on the clinical literature. At this stage, we default to those judgements in making a judgement on when we would use a particular agent in a particular setting. That will be taken away from us.

Senator RYAN —We have heard from a number of other witnesses that, if cost was an issue to a patient through a therapeutic group premium, clinicians would have the opportunity to ring Medicare Australia and seek an authority because it was clinically inappropriate for there to be a change. Do you have any comment to make about that system, its accessibility, whether it is widely used and whether you use it or not?

Dr Inderjeeth —I certainly have not used that system to look for an agent outside of that group. It is substitution, I guess. I tend to specifically request a particular agent and tick the appropriate box to ensure that a particular agent is supplied to my patient.

Prof. Oakley —I was not aware of the system.

Senator MOORE —I am interested in the terminology that all of you have used about you being forced to change the medication that someone is on. I just do not understand why this particular process would force anyone to prescribe medication with which they were not comfortable.

Dr Major —To be quite frank, we are not forced into that. The issue arises because, say, if one decides to use risedronate as the treatment of choice, if the patient has to meet a price premium it creates an obstacle. As many of the people who are prescribed these drugs are elderly or pensioners and so forth, the extra cost can be a significant hurdle. That would be the main issue in that regard.

Senator MOORE —Were you unaware of the waiver process?

Dr Major —I certainly was not aware of what Senator Ryan was just outlining—that is, that we can ring up and request a special dispensation for the patient.

Senator MOORE —You can request that, yes.

Dr Major —That way, they will receive the requested drug—

Senator MOORE —Without the added cost.

Dr Major —Yes.

Senator MOORE —And none of you doctors were aware of that process?

Dr Major —No, I was not.

Dr Inderjeeth —No, and my concern would be that we are talking about a high-volume treatment. If we make a judgment that we want a specific agent then there is a specific amount of administrative responsibility that will go with this. Because of the volume of patients that we see that require a choice of one or the other of these agents, the administrative burden in trying to do that would be pretty problematic. We cannot assume that these two are interchangeable in clinical practice anyway.

Senator MOORE —Have you asked about it, to presume the administrative impost it is going to cause?

Dr Inderjeeth —I have never had to ask for it because, to date, we have been allowed to prescribe whichever agent we prefer. We have never had to do that in the past. If the regulation changes, we will be obliged to do that, which is going to increase that administrative burden. The biggest risk is that some clinicians may decide that the administrative burden is too much to make what they think is an appropriate clinical judgment. The default is saying, ‘Whatever will be will be,’ potentially to the detriment of the patient.

Senator MOORE —So the doctor would make an administrative choice over their professional choice of offering the service to their patient.

Dr Inderjeeth —That is a potential risk. Clinicians are generally time poor and sometimes they make a convenient decision which, as I said, may be to the detriment of their patient. They may have a particular preference. As I said in my dissertation, it was about patients and clinician choices and about matching a particular agent to the patient. But the problem is if it creates a significant administrative burden. I want to refer you to my other statement, which is that this is a condition which is already underdiagnosed and undertreated. If we add in additional administrative burdens, we will further restrict the rate at which patients are offered treatment because of the additional administrative work, or they may simply be prescribed an agent and it will be pot luck because you will get whatever the PBS chooses to give you, even though I may not necessarily think that is the best agent.

CHAIR —I have a family member who has quite significant osteoporosis. At the time of diagnosis, she was prescribed a drug that I understand you do not need to do this for now—and I cannot tell you what the drug’s name is—but the doctor had to get permission to use it. It has just come off that list. So surely doctors are used to ringing up for drugs that in the past you have had to have permission to use? It is one of the ones that she uses once a week. I do not know what its name is, but I can tell you that the doctor had to get permission to use it.

Dr Inderjeeth —Thank you for that. One of the reasons that the regulation was changed was that it was seen as an unnecessary barrier to prescribing. We identified that only about 20 or 30 per cent of patients were getting that particular treatment. So by restricting it they are creating barriers for general practice. They are treating diabetes, hypertension and dementia, and osteoporosis tends to be ignored. We know that this is not an inconsequential disease. There is a 20 per cent mortality rate. There is a 40 per cent disability rate, requiring nursing home care, and 60 per cent of patients require care. It costs $20,000 for a hip fracture. It costs $40,000 in a nursing home. These are potentially preventable conditions, or, at best, we can reduce the rate at which these complications occur. If we put in additional barriers they will not be treated. We know that they are badly treated already. Putting in additional hurdles will make it even less likely that they will be treated. We will actually be going backwards rather than forwards in terms of treating what we think is a treatable and/or preventable disease.

CHAIR —Thank you, Doctors. Your time is very much appreciated.

Dr Inderjeeth —Thank you.

[1.50 pm]