In the UK, new therapies must be approved by the Medicines and Healthcare Products Regulatory Agency (MHRA). The National Institute for Health and Care Excellence (NICE) is then responsible for recommending if any approved therapy will be listed through NHS England, and who will be eligible for it.
Although NICE and NHS England should be applying similar levels of scrutiny across all fields, from cutting-edge gene therapy to innovative aspects of fertility preservation, some innovations seem to slip through cracks.
Casgevy, a one-time genome-editing therapy, offers a possible cure for sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT). In November 2023, the MHRA approved Casgevy for patients aged 12 and above suffering from recurrent painful crises, which occur when the microcirculation is obstructed by sickled red blood cells, causing ischemic injury to the organ supplied, and resultant pain (see BioNews 1216). However, in March 2024, NICE preliminarily recommended that Casgevy is not to be reimbursed due to uncertainties in the clinical and economic evidence, or, in other words, its cost-effectiveness (see BioNews 1231).
For the treatment, haematopoietic stem cells from a patient are collected, genetically edited in the lab, and transplanted back. The patient, in the meantime, is subjected to a round of chemotherapy. Ongoing clinical trials CLIMB-121 for SCD (NCT03745287) and CLIMB–111 for TDT (NCT03655678) have demonstrated high efficacy. However, it is not known for how long the effects would last. With an estimate of 2000 SCD and TDT patients in the UK being eligible for the treatment, and a cost that might be near £2 million per patient (before the price could be negotiated down), it seems reasonable that we should have more data on the long-term sustainability of the treatment.
You may also remember the yearslong back-and-forth between NICE and the manufacturers of CAR T-cell therapies Yescarta (Gilead) and Kymriah (Novartis). Similarly, in September 2018, NHS England announced a ground-breaking personalised therapy for children with a certain type of cancer which costs around £282,000 per treatment and is approved to treat patients up to 25 years old. It took almost five years until the therapy was approved in April 2023 for people aged 26 years and older.
This meticulous scrutiny of the efficacy and cost-effectiveness of medical treatments and procedure was also evident in evaluation of ovarian tissue cryopreservation (OTC), a method used to preserve a woman's fertility by freezing and storing ovarian tissue.
OTC is currently offered in various countries, including Belgium, Germany, Denmark, the United States, Australia and Canada. For young women or prepubertal girls facing urgent gonadotoxic treatment that carries a high risk (at least 80 percent) of infertility and that are unable to undergo egg freezing procedure, this is the only viable option. If after the treatment, the patient goes into remission, remaining cancer-free, and fertility is compromised, the cryopreserved tissue could be transplanted back. If the transplanted pieces of ovarian tissue get vascularised, the ovarian tissue will become functional, restore the menstrual cycle, and the women may be able to establish a pregnancy. More than 150 babies have been born worldwide from women who underwent this procedure. Unfortunately, in the UK, only a limited number of hospitals provide this valuable option to cancer patients (see BioNews 1171).
A number of clinicians proposed, without firm evidence of benefits for the patients, that this technology can be used to delay menopause and lower the risk for a range of associated and age-related conditions (see BioNews 1011). It was not a surprise that on 21 September 2022, NICE stepped in to prevent healthcare providers from using this technology on unsuspecting patients. It stated that the evidence on the safety and efficacy of removal, preservation and subsequent reimplantation of ovarian tissue to prevent symptoms of menopause is inadequate in quality and quantity, and that this procedure should be only done as part of a formal research study.
As part of the work to support the case for OTC to attain NHS England commissioning, a market engagement exercise was undertaken in February 2023. The decision to support commissioning of the service was confirmed in August 2023, and on 21 September 2023, NICE announced that the removal, preservation and reimplantation of ovarian tissue for restoring fertility after gonadotoxic treatment may be used if standard arrangements are in place.
All sounds well thought out and in accordance with NICE's cost-effectiveness trademark. Women of reproductive age and prepubertal girls will finally get an opportunity to preserve their fertility using a technology that has been proven to be safe and effective and that was not previously available.
However, in December 2023, when NHS England announced a market engagement for identifying the service providers, the finalised proposed model for delivery and the requirements of the service specification, beside ovarian tissue, also included cryopreservation of testicular tissue.
Several centres worldwide, including two in the UK, are preserving testicular biopsies for patients who cannot produce sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. No successful outcome of the cryopreserved testicular tissue for restoration of fertility has ever been reported anywhere in the world. Therefore, this procedure should not be offered to the patient without substantial evidence of efficacy, unless it is part of a formal research study. Stating otherwise is misleading and gives false hopes to the vulnerable population.
It seems that testicular tissue cryopreservation has never been reviewed by NICE. It is difficult to believe that this procedure and the way that it is offered to patients would pass scrutiny of NICE, knowing their exemplary insistence on efficacy and cost-effectiveness.
One might argue that testicular tissue cryopreservation is inexpensive and would not make a big dent in the NHS budget. However, the procedure is invasive, the outcome is uncertain, and the money is public; the standard approval pathway should therefore be followed. Until proper scrutiny and approval is in place, cryopreservation of testicular tissue should not be included in NHS service specifications.
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