On June 1, 2009, Then Health Services Minister George Abbott officially announced the AMD Expansion Treatment Program designed to fund the high costs of intravitreal injections for patients with the wet form of age-related macular degeneration (AMD). While the name of the program has been changed to the BC Retinal Diseases Treatment Program (PRSTP,) the BC provincial government continues to fund this program to treat patients afflicted with Advanced Macular Degeneration (AMD), Diabetic Macular Edema (DME) and other retinal diseases with anti-vascular endothelial growth factor (anti-VEGF) medicines.
We have learned that unfortunately, many patients receiving treatment under this program remain inadequately aware of potentially serious risks to their vision health that have been raised by growing number of ophthalmologists, and also the BC Society of Eye Physicians and Surgeons.
Patients who have become aware of potential risk involved with treatment provided under the PRDTP, may be experiencing a significant degree of anxiety, as it remains unclear whether the provincial government is taking adequate steps to address risks associated with this provincial Ministry of Health funded program. We are also aware that a program adopted by Alberta, the Retina Anti-Vascular Endothelial Growth Factor Program for Intraocular Disease (RAPID) is subjecting AMD, DME and other patients requiring anti-VEGF treatment in that province, to similar risks as being experienced in BC.
Access for Sight Impaired Consumers takes the position that the growing and serious vision health issue associated with the PRDTP and RAPID programs must be fully addressed, and there is an urgent need for increased public awareness and debate on what the risks are, what is causing them, how they are affecting patient health outcomes and how these risks should be addressed. Based on the volume of feedback that we have received from patients and medical professionals, we believe that the governments of British Columbia and Alberta need to act quickly to address concerns with these programs.
Access for Sight Impaired Consumers is taking action for the purpose improving government policy on the treatment of retinal diseases, by helping patients to become educated and informed of the risks they are being subjected to, and actions they should insist their governments take to address and reduce those risks.
Details obtained through Freedom of Information requests submitted to BC’s Provincial Health Services Authority by Access for Sight Impaired Consumers in 2012 confirmed three areas of concern under the fiscal 2010/2011 program about the treatment options for AMD. The 3 areas of concern still exist in the PRDTP as of February, 2022.
3 items we are concerned with:
1. The inclusion of an anti-VEGF medication not approved by Health Canada for intravitreal injection is funded as a preferential treatment under both the BC PRDTP and Alberta’s RAPID programs:
The BC and Alberta provincial governments continue to require preferential use of a drug developed and approved for the treatment of colorectal cancer known as Avastin®. The Health Canada Product Monograph clearly states in a highlighted warning that Avastin® is not approved for and should never be used for intravitreal injection.
Both BC and Alberta programs only allow funding for a select group of Retinal Specialists to administer anti-VEGF medications via an intravitreal injection. The drugs Avastin®, Eylea® and Lucentis® are all funded under these programs.
However, because off-label Avastin® is the less costly of the three treatment options, both BC and Alberta programs require that Retinal Specialist physicians participating in those programs use it for 90% of patients they are treating. According to internal government documents we have obtained, physician income from the program is significantly reduced if the 90% quota for Avastin® is exceeded. This is the case even though Avastin® appears to be the least safe of the treatment options.
Both Health Canada and the drug manufacturer (Genentech/Roche) have issued warnings aimed at health care professionals of potentially serious (possibly fatal) side effects (e.g. strokes, heart attacks and/or blood clots) that could lead to hospitalization or worse. A similar release from Health Canada and Roche was made public to advise consumers at the same time.
We’re confirming what we’ve learned by sharing the latest information extracted from page 5 of a 95-page Health Canada Monograph for Avastin® released on January 14, 2021, which reads in part:
“Serious Warnings and Precautions
AVASTIN is not formulated and has not been authorized for intravitreal use.
Local and systemic adverse events have been reported in the post-market setting with unauthorized intravitreal use.
Individual cases and clusters of serious ocular adverse events affecting multiple patients have been reported from unauthorized intravitreal use of AVASTIN following variable and non-validated methods in compounding, storage, and handling of AVASTIN vials authorized for intravenous administration in cancer patients. These events included infectious endophthalmitis (some cases leading to permanent blindness, one case reported extraocular extension of infection resulting in meningoencephalitis), intraocular inflammation (such as sterile endophthalmitis, uveitis, and vitritis) (some cases leading to permanent blindness), retinal detachment, retinal pigment epithelial tear, intraocular pressure increased, intraocular hemorrhage (such as vitreous hemorrhage or retinal hemorrhage), conjunctival hemorrhage.”
We acknowledge the foregoing is an extract only and not a complete disclosure of the monograph on the Health Canada site. Should you wish to read more, you can download or view the latest Avastin® monograph on the Health Canada web site.
2. Financial incentive for physician participants program (primarily Retinal Specialists) to use a less expensive off-label medication:
Section 23(b) of the BC Retinal Diseases Treatment Program contract (dated April 1, 2015 – but still in effect according to a recent Freedom of Information Request response) with participating Retinal Specialists, states that the amount available for payment to Retinal Specialists participating in the program equals the net amount remaining after the expense of medication that is used in the program is deducted from the program budget. Simply put, this means that the amount available for fees paid to program participants would be significantly higher if they minimize the overall medication expense.
As taxpayers this arrangement appears to be sound policy to help control health care costs. And we might have agreed if the lowest cost medication was in fact approved for intravitreal injection by Health Canada. However, the least expensive option Avastin® is not approved by Health Canada for treatment of AMD or DME. And warnings have been issued by Health Canada advising against injecting Avastin® into the eye.
Further, it is our view that medication cost savings should not contribute to a financial benefit for physicians to the degree that it may influence the choice of medications that are used. This is a direct conflict of interest by any measure and does not exist in any other area of medicine funded by our provincial health care systems.
We question what treatment patients would choose from the options available for these serious retinal diseases, if presented with full disclosure including all the facts both positive and negative of each option.
Patients requiring anti-VEGF treatment may wish to view an informative video by Dr. Sanjay Sharma of Queen’s University reporting for Insider Medicine within the British Medical Journal.
We also suggest reviewing media reports of serious adverse events that have been identified by the BC Society of Eye Physicians and Surgeons and brought to the attention of the Minister of Health in 2019.
3. Lack of availability of new treatments within the programs:
Neither the BC or Alberta Ministries of Health have included the newest anti-VEGF therapy as a treatment option within their PRDTP or RAPID programs. Coverage for the new drug called Beovu® (brolucizumab) has been negotiated with the pan-Canadian Pharmaceutical Alliance (pCPA). The pCPA web site states that this organization is an alliance of the provincial, territorial, and federal governments that collaborates on a range of public drug plan initiatives for the purpose of increasing and managing access to clinically effective and affordable drug treatments.
The pCPA website states that one of their key roles is to conduct joint negotiations with the manufacturer for brand name and generic drugs in Canada in order to achieve greater value for publicly funded drug programs and for patients through its combined negotiating power.
The objectives of the pCPA are to:
- increase access to clinically effective and cost-effective drug treatment options;
- achieve consistent and lower drug costs for participating jurisdictions;
- reduce duplication of effort and improve use of resources; and
- improve consistency of decisions among participating jurisdictions.
On the pCPA website, they indicate that they has concluded negotiations for Beovu® with the manufacturer with a ‘letter of Intent’ on August 31, 2021 which means that provinces in Canada will be providing Beovu® as a covered benefit.
We are pleased that Beovu® is already a provincially funded benefit in other provinces including Ontario and New Brunswick and we believe this new treatment should be made available to patients in Alberta and BC under their respective retinal diseases programs.
Actions taken by Access for Sight Impaired Consumers to address patient safety issues
In September 2012 we met with Assistant Deputy Minister Barbra Walman – Pharmaceutical Services and her colleague, Dr. Eric Lun, Executive Director – Drug Intelligence Branch, Pharmaceutical Services Division .to discuss the foregoing concerns. While the meeting was beneficial in terms of building bridges and establishing a relationship with the government’s decision makers for the program, we were informed that:
- Statistical data kept by the Ministry reports that Avastin® is used 75% of the time when an intravitreal injection is administered by a retinal specialist;
- The Ministry is monitoring all reported incidents of side effects from the use of drug therapies and to date have had minimal occurrences reported;
- The current AMD Expansion Program is costing the Ministry approximately $13million per year while the use of alternate anti-VEGF medications exclusively would increase the costs to approximately $41million; and
- The Ministry is currently satisfied with the program and has no immediate plans to alter its execution.
Access for Sight-Impaired Consumers immediately contracted with a national research firm to undertake a telephone survey of residents in British Columbia living with AMD to determine how people felt about issues relating to AMD treatment in the province. We discovered and shared the survey results of the perceptions of treatment for AMD in British Columbia which confirmed that BC’s AMD patients were not getting full disclosure of treatment options. Nor were they receiving a thorough explanation of the possible side effects of the drug therapy that their physician has selected on their behalf.
We also questioned whether the patients in British Columbia who took part in our survey were fully aware of their right to choose their treatment options under the BC Health Care (Consent) and Care Facility (Admission) Act? In other words, if a patient agreed to be treated with an intravitreal injection, did they know it was their legal right to receive the medication of their choice following full disclosure of the pros and cons of each option by the retinal specialist.
Aside from the actual survey and with the results in mind, we further questioned the extraordinary yet undetermined costs resulting from added medical intervention or hospitalization required due to potential side effects associated with the less expensive medication option.
We sent a follow-up letter to Assistant Deputy Minister Barbara Walman along with a copy of our “Perceptions of Treatment for Wet AMD in British Columbia” survey results in April 2013. We highlighted the fact that the survey clearly showed a majority of patients in British Columbia were not being made aware of available AMD treatment options nor what intravitreal medication they had received. Further to this, the survey revealed a majority of patients in BC were neither given a treatment option nor seemed aware of the potential for serious adverse effects because of treatment with whatever medication they had received.
In our letter to the ADM, we asked her to comment on the survey results and to supply an explanation for the fees paid to specialists in BC versus the much lower fee that is paid in Ontario or other provinces for the identical procedure.
We share the response received from the ADM’s office in June 2013 which we found to be both puzzling and misleading.
As we prepared to upload and release the survey findings on our web site, we submitted our second Freedom of Information request to the Provincial Health Services Authority in April 2013. Once again, we requested a copy of the 2011/2012 AMD Expansion Program to determine what changes or modifications to the previous year’s program may have occurred. What we received reflected only minor modifications To the program from the year before. Subsequent Freedom of Information requests were submitted again in the years that followed enabling us to watch for any significant modifications to the program over the years. Our most recent request for an update resulted in a response from the BC government to the effect that the contract has not changed since 2015/16 and that the program design outlined and contract is still in effect to the present day.
A Look at More Current Activities
As stated earlier, Access for Sight Impaired Consumers has learned that many of these patients receiving intravitreal injections remain inadequately aware of serious risks to their vision health that have been raised not only by growing number of ophthalmologists, but also the BC Society of Eye Physicians and Surgeons. Patients who have become aware of these risks are experiencing a significant degree of anxiety, as it remains unclear whether the provincial government is taking adequate steps to address those risks.
To that end we are once again undertaking a deep dive into both BC’s Retinal Diseases Program and Alberta’s Retina Anti-Vascular Endothelial Growth Factor Program for Intraocular Disease (RAPID). Five separate Freedom of Information requests have been submitted to the Provincial Health Services Authority in BC and drafts are pending with respect to Alberta’s RAPID program.
This is far from the final chapter on this file, and we will continue to dig deep into these programs to uncover more details. We will post updates as more information becomes available.
Some Facts of General Interest
- When submitting an application for approval of a medication or medical device to Health Canada, their focus is on two aspects of the application; “Is the medication or device effective in treating a patient for the purpose the manufacturer claims?” And “Is it safe when used for the specific treatment stated in the manufacturer’s application?”
- Following review and analysis of the research data accompanying the application, the medication or device may be approved by Health Canada for the purpose intended. Health Canada posts medication ‘monographs’ and also ‘alerts’ when irregularities or numerous adverse effects arise.
- Health Canada does not dictate how a medication or device must be used. That decision rests solely with the treating physician and must be done in consultation with and ‘informed consent’ of the patient being treated. With that said, it is important we state that retinal specialists are not doing anything illegal under Canadian law by using Avastin® as an intravitreal treatment for wet-AMD or DME.
- Our concern rests with the degree of understanding by the patient being treated with an unapproved medication, and whether or not there is true informed consent based upon the patient’s understanding of the treatment options available and what the physician plans to treat them with. This is particularly an issue when the Health Canada approved monograph contains specific warnings advising against the use of a drug for a specific purpose as in the case of intravitreal administration of Avastin® which is something that the Health Canada monograph recommends against for safety reasons.
- In Dr. Sharma’s video, he makes a comparison between two intravitreal medications, Avastin® and Lucentis®, the latter being distributed under license to Novartis Pharmaceutical (Canada) by the manufacturer, Genentech. Be aware that two other treatment options are also available for AMD; Bayer’s Eylea® and a newer medication Beovu® (also known as brolucizumab) – the latter being distributed by Novartis Pharmaceuticals.
- Avastin® was developed to treat colorectal cancer and lung cancer. It uses a mouse anti-body at the root of its molecular structure. The molecules look somewhat like a “Y” and are effective in treating these cancers in that they reduce the production of blood vessels required by cancer cells as an anti-vascular endothelial growth factor (anti-VEGF.) During the development of this molecular structure the manufacturer kept the full length of the anti-body given it was being developed to treat two specific cancers. The longer the molecules are retained in the body, the greater the efficacy of the medication. You may be asking “How does an anti-VEGF medication such as Avastin® treat these two cancers?” What an anti-VEGF medication does is essentially starve the cells by restricting any vascular growth around the cancerous cells and thereby reducing the amount of blood reaching those cells. For this reason, the longer these molecules are in the body, the more effective the medication becomes and the amount of medication over the long term is reduced. With all this said we reiterate Avastin® was developed to treat colorectal cancer and lung cancer. It was never developed or recommended by the manufacturer or approved by Health Canada as an intravitreal injection into the eye.
- The size of the molecules in this anti-VEGF medication is an important factor in the efficacy of the medication. The smaller the molecules, the greater their ability to “penetrate” and get into areas of the body where most needed; by example you can’t shove a golf ball through a garden hose, but a grain of sand will find its way through with ease.
- The molecular structure of some of the previously mentioned anti-VEGF medications are between approximately one-third and one-sixth the size of an Avastin® molecule.
- In simple medical terms, imagine an affinity factor of 1 is assigned to an Avastin® molecule; in other words the ability of the Avastin® molecule to grab onto the VEGF molecule is rated as 1. Dr. Sharma’s reference to Lucentis® has an affinity factor 140 times greater of attaching itself to the VEGF molecules making it far more effective as an anti-VEGF medication resulting a smaller dose requirement. A similar principal can be applied to the other newer medications Eylea® and Beovu®.
- The binding and affinity properties of these molecules also affect the frequency of administration, and the number of times a patient will need to go in for an injection to effectively treat their condition. Frequency of dosing may be one of the factors associated with some of the side effects that BC ophthalmologists have expressed concern about. These differences between treatments should be explained to the patient to obtain true informed consent based on an understanding of the pros & cons of each treatment alternative.
- The United States Pharmacopeia (USP) organization has established strict guidelines with respect to the formulation of medications that will be injected into the body including intravitreal injection into the eye. Inasmuch as Avastin® was not developed as an anti-VEGF medication for the treatment of eye diseases, it is not required to meet the USP guidelines regarding its formulation.
- Avastin® is formulated to be packaged in 50ml/50cc (cubic centimeter) vials that were developed by the manufacturer and approved by Health Canada for single use only as a cancer treatment. When Avastin® is used as an unapproved medication for injection into the eye, the single use vial for cancer requires an extra procedure known as “vial splitting.”
- Vial Splitting is a practice that is not recommended for any product supplied in a multidose format due to the risks involved that can seriously affect product integrity, including bacterial or viral contamination, particulate matter contamination, product stability in a non-approved container such as a plastic syringe instead of a glass vial, etc. Vial splitting can be particularly hazardous when it involves sterile products that will be used for intravitreal injection. Dosage amounts will vary. However, using Dr. Sharma’s statement that approximately 1/20 of a milliliter is the average dose required, a single use vial designed for cancer treatment will be split as many as 50 times or more to create individual doses for ophthalmic use. Each time the vial stopper of a single dose vial is breached to draw a dosage into the application syringe, the potential for contamination is present which may be the cause of Dr. Sharma’s references to severe eye pain, pus in the eye and other adverse effects such as increased intraocular pressure and glaucoma as has been raised as a concern by the BCSEPS organization on behalf of patients in BC who are being treated under the PRDTP structure.
- Vial splitting under the respective anti-VEGF programs In BC and Alberta is also required for the products Lucentis® (single use vials split 3:1) and Eylea® (single use vials split 4:1) even though both of those products are available as syringes specifically developed for single use from the manufacturer. Vial splitting is usually done by a pharmacy which then sends syringe(s) meant for individual doses to the retinal specialist.
- Let’s also take a moment to understand what is meant by the half-life of a medication. The half-life of a drug is the time it takes for a drug’s active substance in your body to reduce by half. This depends on how the body processes and gets rid of the drug. It can vary from a few hours to a few days, or sometimes weeks. The Avastin® molecule stays in the body for up to twenty-one days which is good given its purpose as a cancer fighting medication. The half-life of Lucentis® is fifteen hours which means there is theoretically a much lower risk of systemic adverse drug reaction such as strokes, heart attacks and/or blood clots.
- The Lucentis® molecules “grip” the VEGF molecules much tighter which prevents them from aimlessly floating throughout the body whereas the lesser gripping Avastin® molecules may be present in the body for up to 21 days. Because of this latter point that likely formed the basis for Health Canada and Genentech to issue their warnings and to further state that Avastin® should not be used as an anti-VEGF medication for injection into the eye.
- Again, all of these differences between treatments should be explained to the patient to obtain true informed consent based on the patient’s understanding of the pros & cons of each treatment alternative the physician wants to use.
For your download and review, we are pleased to provide informative links for the monographs for:
- Avastin® – latest monograph revision: January 2021
- Beovu® – latest monograph revision: December 2021
- Eylea® – latest monograph revision: September 2021
- Lucentis® – latest monograph revision: December 2021
Access for Sight Impaired Consumers does not present any of the content on this page as medical advice. It is information that we have obtained and share for the purpose of building awareness only. We recommend you conduct your own research into current treatments for the retinal disease that is of interest to you.