Fearless pharma blogger Maxine Vaccine considers the significance of a report highlighting the ‘information gap’ between patients and their doctors regarding side-effects.

Last month I wrote a blog about the ‘cascade’ syndrome of patients taking medication to deal with the side-effects of other medication. It was based on a handful of individual cases within my select circle of friends. Now a major study, focusing on treatment for a life-threatening illness, has highlighted the issue of unreported side-effects in a way the industry cannot afford to miss.

A team from Northwestern University in the USA questioned 686 women who had been prescribed aromatase inhibitors (AIs) for a five-year period as treatment for breast cancer. AIs inhibit the production or action of oestrogen, a hormone that promotes the growth of about two-thirds of breast cancers. Following successful treatment by surgery, chemo and/or radiotherapy, the use of AIs has been shown to help prevent recurrence of the cancer.

The study found that 36% stopped their medication because of side-effects such as joint pain, hot flushes and nausea. However, previous studies had shown that only 5% of women given AIs reported moderate to severe side-effects.

Dr Lynne Wagner, who led the study, commented: “There’s a significant gap between patient-reported symptoms and provider-reported symptoms. That gap widens when we’re talking about more subjective symptoms, things like pain or fatigue that only a patient can report.”

She also noted that “clinicians consistently underestimate the side-effects associated with treatment,” while “patients don't want to be complainers and don't want their doctor to discontinue treatment”. So there is a conspiracy of silence that results in poor compliance, with a negative effect on clinical outcomes. And AIs are unlikely to be an isolated case.

Two further points are worth noting. Those women still suffering side-effects from their earlier, more radical treatment were more likely to give up taking AIs, because their endurance threshold was lower. And the likelihood of stopping the medication increased steadily with time – because over a period of years, the patient’s endurance runs out and their subjective sense of the risk-benefit equation changes.

You may be wondering: this is my fault how? If a drug is effective, surely making good decisions about its use is down to the doctor and the patient, not the supplier? But if we can step back from the (rarely helpful) question of blame, there are important lessons for pharma in this study.

For a start, every patient who stops taking a drug without notifying their doctor is negatively affecting the clinical outcomes data. If they’re lucky and their clinical outcome is not affected, clinicians and suppliers are still left with an incomplete picture of the drug’s risk-benefit profile, which helps nobody and is a step back from patient-centred care.

As more and more patients take powerful medications on a long-term basis, reliable data on side-effects – enabling them to be treated through dose adjustment and other strategies – is the only way to get the optimum patient benefit out of the drugs that exist. We need to know much more about how side-effects accumulate with time, how multiple medications affect the patient in combination, and what the best compromise dosage level is for each medication and each patient.

That calls for better sharing of information between companies, healthcare providers and patients, rather than quasi-antagonistic relationships based on competition. The human body is not a marketplace.

Maxine Vaccine is keen to receive your feedback on these and other pharma industry issues. Be nice (but don’t be NICE)!

Over a third of women prescribed a long-term breast cancer therapy stop taking it because the side-effects are intolerable, US researchers have said.

Aromatase inhibitors (AIs), given to women following surgery, chemotherapy or radiotherapy treatment for oestrogen-sensitive breast cancers, has side-effects including joint pain, hot flushes and nausea.

The study has drawn attention to the gap between clinicians’ reporting of drug side-effects and the subjective experience of patients.

About two-thirds of breast cancers are oestrogen-sensitive. AIs, which either block the production of oestrogen or block its action on receptors, have been shown to reduce the risk of breast cancer recurring.

A team from Northwestern University questioned 686 women who had been prescribed aromatase inhibitors for up to five years. It found that 36% stopped their medication because of increasing side-effects. Those still experiencing side-effects from chemotherapy or radiotherapy were more likely to stop taking AIs.

In previous studies, doctors had reported that only about 5% of patients given AIs had moderate to severe side-effects.

Dr Lynne Wagner, who led the study, commented: “There’s a significant gap between patient-reported symptoms and provider-reported symptoms. That gap widens when we’re talking about more subjective symptoms, things like pain or fatigue that only a patient can report.

“Clinicians consistently underestimate the side-effects associated with treatment. Patients don't want to be complainers and don't want their doctor to discontinue treatment.”

“It is worrying if breast cancer patients are stopping life-saving treatment early without consulting their doctor,” said Dr Susie Jennings, Senior Policy Officer at UK charity Breakthrough Breast Cancer. “It is important there is a continued discussion throughout treatment.”

Draft NICE guidance does not recommend the routine use of AstraZeneca’s anti-oestrogen drug Faslodex (fulvestrant) in the NHS to treat certain types of breast cancer.

Faslodex was authorised in 2010 for marketing as an alternative to aromatase inhibitors to delay the growth of oestrogen-receptor-positive, locally advanced or metastatic breast cancer in postmenopausal women who have already received anti-oestrogen therapy (such as tamoxifen).

NICE’s Independent Advisory Committee has concluded that the drug is not significantly more effective than existing treatments, and so its routine use would not be a good use of resources.

The Committee judged AstraZeneca’s claim that Faslodex could extend life relative to the aromatase inhibitors anastrozole and letrozole to be uncertain as network meta-analyses showed no statistically significant differences.

In addition, they found that Faslodex delayed cancer growth more effectively than anastrozole but not more so than letrozole. An incremental cost effectiveness ratio of £35,000 per QALY gained for Faslodex 500mg compared with anastrozole was estimated, but with “considerable uncertainty”.

The draft guidance thus recommends that NHS doctors should not prescribe Faslodex as an alternative to aromatase inhibitors in relevant cases – but that women who are currently receiving Faslodex should be able to continue to do so until they and their doctors decide to stop.

Sir Andrew Dillon, Chief Executive of NICE, commented: “While there is evidence that fulvestrant can delay the growth of breast cancer, our independent committee found that when used according to its marketing authorisation, its effectiveness is uncertain compared to aromatase inhibitors, which are currently the preferred treatment options on the NHS.

“As fulvestrant has not been proven to be cost-effective, we cannot justify diverting NHS funds from other areas of healthcare in order to fund its use.”

The draft guidance is open to appeal until 24 November. NICE hopes to publish final guidance in January 2012.