HRT – Too great a risk ?
pharmafile | November 4, 2003 | Feature | Research and Development |Â Â HRT, clinical trialÂ
The last 15 months have seen the image of HRT change from a miraculous medicine to a risky range of products which can significantly increase the chances of life threatening diseases in women.
The problems began in July 2002 in America when the National Institute of Health (NIH) terminated a trial on combination hormone replacement therapy after finding an increased risk of breast cancer for women on the treatment. The study was conducted on more than 16,000 healthy post-menopausal women with a uterus, and focused on combined Oestrogen/Progestogen treatments such as Wyeth Premarin and Prempro. It was designed to investigate the effect of Prempro on the prevention of hip fractures and heart disease.
An original completion date of 2005 had been anticipated, but the study was terminated after results highlighted a 26% increase in breast cancer, a 41% rise in strokes and a 29% increase in heart attacks for women on the drug. It was not a totally negative picture however, as findings did support positive benefits of the treatment such as reduced hip fractures and cases of colorectal cancer. On balance the NIH concluded that the benefit ratio was simply not great enough to justify use of the drug.
Another NIH study at the end of 2002 discovered that the risk of developing breast cancer significantly drops when women stop taking the drug. Four thousand post-menopausal women, of whom approximately 50% had been diagnosed with breast cancer were questioned about their use of continuous combined treatments. The results showed that women on the treatment were one and a half times more likely to develop breast cancer and this risk increased the longer the women were on HRT. One positive finding was that this risk returned to normal levels six months after stopping combined HRT treatment. It was also determined that risk levals dropped regardless of how long these women had previously been on HRT treatment.
Other forms of HRT treatment were also investigated yielding mixed results. When Oestrogen and Progestogen are taken individually on differing days of the month, no increase in risk was found in developing breast cancer, but instead an increase in risk of endometrial cancer was observed. Similarly, women taking oestrogen-only products were not anymore likely to increase their risk of breast cancer but may have a higher chance of developing ovarian cancer.
The most recent research results released by Cancer Research UK in August 2003 known as the Million Women Study is unlikely to lessen the negative press surrounding HRT treatments. Data on more than one million women between the ages of 50 and 64 (50% were using a variety of HRT) found more than 9,300 cases of breast cancer and 637 deaths among the sample. Similar to the American study investigators found that post-menopausal women using continuous combined treatments were twice as likely to develop breast cancer compared to non-users. In addition, findings indicated an increased risk of developing cancer by 45% and 30% for users of tibolone and oestrogen-only HRT respectively. It was also determined that women on HRT were 22% more likely to die from cancer compared to non-users.
Physicians have always been aware of the increased risk of breast cancer linked with HRT, but the benefits for the heart and bones were thought to outweigh the risks for post-menopausal women. The decision to start a course of HRT treatment proved difficult for both patients and GPs even before the recent findings. Undoubtedly, such press has made this crucial choice even tougher. It is universally accepted that with almost all medicines there are associated risks. The resultant effect of the recent studies has been to highlight in more detail the risks of HRT treatment, resulting in patients and GPs being more cautious and considering in greater depth the risks associated with HRT products and treatment.
Market outlook
As with all health scares, it is difficult to predict how the market and the products involved will be affected. It is unsurprising that an onslaught of over twelve months of negative press surrounding the HRT market has had a substantial impact on HRT product usage and consequently sales. However, the picture may not be totally negative for overall pharmaceutical sales. For a market such as Women's Health, such negative press could benefit other treatment areas, for example, osteoporosis. For years women have taken HRT treatment to reduce risks of osteoporosis and patients have seen benefits. However, one may now be seeing a switch from women previously using HRT products for osteoporosis, to simply using osteoporosis products such as Actonel (Procter & Gamble and Aventis) and Fosamax (Merck Sharp & Dohme). It seems that patients may now feel that using HRT products for other diagnoses such as weak bones simply is not worth the risk.
Decline in prescriptions
By considering data from Jigsaw, a salesforce effectiveness tool from Isis Research, one can look at the trends within the HRT market and consider whether the HRT scares truly have had a big impact on GP prescribing behaviour. Firstly, looking at opportunity prescribing (definition: a dynamic decision prescription from the GP; includes newly diagnosed, change drug, add-on, new episode and change dose, all prescriptions except repeats) of HRT products over the past two year you can clearly see a constant decline in overall opportunity prescribing of HRT products from a moving quarterly total (MQT) of 120,000 opportunity prescriptions in September 2001 MQT down to approximately 90,000 opportunity prescriptions in the August MQT this year. This is a 25% decrease in opportunity prescriptions, which surely must be attributed in part to the recent scares. HRT prescriptions were already decreasing before the scare, but the rapid decrease to fewer than 80,000 opportunities by April 2003 MQT must largely be the result of the press criticism in the latter half of 2002.
Looking in more detail at the products which have lost business, it is obvious that the continuous combined group has suffered most in the last two years. Again unsurprising, as it was the continuous combined products at the focus of the study of July 2002, which resulted in the scare. Furthermore, as the study centred largely on Wyeth Prempro (a product only available in the US), the negative impact for Wyeth Prem range of products in the UK, such as Premique was apparent.
It is important to note also that despite the fact that the other classes were not directly targeted by the 2002 studies, scripts for this group have also reduced by around 25% in the time period. It is clear that the HRT trials and the negative press surrounding them have impacted on the entire market and each group of products has seen a reduction in opportunity prescribing as a consequence of this.
Using Jigsaw, it is also possible to look at detailing noise within markets, and when studying the detailing data for the HRT market it is instantly clear that a major drop-off in promotion to GPs has occurred since March of this year. What is also interesting is that detailing remained constant up to the beginning of 2003 despite the initial scare. However, from March 2003 one can see the start of the major drop-off in promotion, almost ten months after the July 2002 study.
Cutting promotion
It is likely that pharma companies did not reduce their detailing levels immediately as they saw it necessary to measure the initial impact. After eight months of monitoring and identifying a continuing decline in opportunity prescribing, pharmaceutical companies perhaps felt that heavy promotion was simply not worth the cost. It is evident that heavy promotion of HRT products did not succeed in halting the overall decline in opportunity prescribing, the damage done was obviously too great to be repaired by promotion alone.
Usage falling
A further indication of the decline in usage of HRT products can also be seen from the breadth and depth analysis carried out using Jigsaw. Firstly, looking at the percentage of GPs prescribing continuous combined HRT products, it is evident that the proportion of the UK GP population using the products has dropped from 77% in the July 2002 Moving Annual Total (MAT), to 68% in the August 2003 MAT. Furthermore, the depth of usage has decreased as well, with the average number of scripts written by a GP dropping from 4.9 to 4.3. This indicates that those GPs who do still prescribe the continuous combined products are tending to reduce the amount they prescribe, perhaps more cautious due to study results or fewer patients requesting HRT treatment.
Breadth and depth analysis for the osteoporosis market is also considered, and the opposite picture to the HRT products can be seen. Since the July 2002 MAT the breadth of usage has increased to 73% and the depth of prescribing has increased from 4.3 to 4.9 scripts for GPs. This could again be an indication that women previously prescribed HRT products for osteoporosis are now being given osteoporosis products as doctors minimise chances with risks associated with HRT products.
Recent news suggests that sales lost to osteoporosis products may be regained. Results from the Women Health Initiative study shows that Prempro does protect women from hip and spine fractures. The impact of this study on the sales of Prempro for osteoporosis remains to be seen, but it seems likely that the damage has already been done to GP confidence in prescribing HRT products. Despite some promising results, a lot more positive publicity will be needed to remove the negative image of HRT products in the minds of women, created by the destructive press coverage.
The HRT story has undoubtedly been a negative one over the last 15 months. For pharmaceutical companies with HRT products, such as Novo Nordisk, Wyeth, Schering Healthcare, Orion Pharma and Merck Pharmaceuticals the road ahead is a challenging one. From the dramatic drop in detailing over the last six months it seems that pharmaceutical companies themselves may no longer feel it is worth heavy investment in promotion. However, with the recent levelling off of the opportunity prescription decline, and some recent studies publishing positive results, things may well improve.
It is clear many women do still choose to embark on HRT and believe the risks are outweighed by the benefits gained. For millions of women their quality of life has been dramatically improved by HRT, and many have been on a treatment for over 20 years, experiencing no problems at all. There is no doubt that since the scare and continuous negative publicity, women are thinking more carefully before starting a course of therapy. For conditions such as osteoporosis many women feel HRT products simply are not worth the risk. But with over 80,000 quarterly opportunity prescriptions the HRT market is still a significant one.
It is not all doom and gloom, however. Some positive points have come out of the studies. Women and GPs may now be better educated about HRT and understand the risks associated with it. Therefore the decision to take HRT can be taken with more care with a more considered consultation.
Although negative press did result in a 'scare' increased awareness and education of HRT can only be a positive result for the pharmaceutical industry and patients.
Sean Cheung and Claire Taylor are analysts with the Healthcare Intelligence Systems team at Isis Research. For more information please contact Louisa Miles on 0208 2466200 or e-mail louisa.miles@isisresearch.com
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