Memorandum by Insulin Dependent Diabetes Trust (PI 30)

/Home/Diabetes Treatment/Diabetes Drug Treatment/Insulin/Insulin Drug Warnings & Precautions

Memorandum by Insulin Dependent Diabetes Trust (PI 30)
Parliament.uk Publications and Records

INTRODUCTION

The Insulin Dependent Diabetes Trust is a registered charity offering information and support to people with diabetes and their families. The Trust formed in 1994 as a direct result of the adverse effects experienced by a significant number of people to synthetic insulin made by genetic modification, introduced in 1982.

Synthetic GM "human" insulin was introduced into the market without long-term safety data and as shown in the Cochrane Review,[115]114 without scientific proof of advantage over existing purified animal insulins with their long history of safety and efficacy. Nevertheless, the significantly more expensive synthetic GM insulin became first line treatment for insulin requiring diabetes and the adverse effects experienced by at least 10% of patients (30,000) have been largely ignored or disputed by both the medical profession and the regulatory authorities.

The vast majority of patients have not, and are not, given the treatment choice of animal or synthetic GM insulin which should be theirs by right and nor have they been provided with information about the risks and benefits of all insulin types so that their choice is informed.

It is difficult to find an explanation for this situation which may have an effect on the health of patients, on their ability to have an informed choice of treatment and on the overall cost of diabetes to the NHS. We believe that in part the explanation must be due to the influence of the pharmaceutical industry.

In their conclusion, the Cochrane reviewers114 expressed concerns that the story of the introduction of synthetic GM "human" insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety. It is for this reason that the Inquiry may wish to consider this "story" as an example of the influence of the pharmaceutical industry over health outcomes and health policies.

THE CONDUCT OF MEDICAL RESEARCH

We are concerned about the quality of industry sponsored research. The Cochrane Review of animal and synthetic GM "human" insulin showed no evidence of benefit and a lack of research to compare mortality and diabetic complication rates which are very important issues for people with diabetes wishing to make treatment choices. However, it also showed that the research that was carried out was "methodologically poor". Yet despite this poor quality research, lack of evidence of benefit and no long-term safety data, synthetic "human" insulin became first line treatment with over 84% of patients transferred to it, too often for no clinical reason.

Our concerns were compounded in 2004, when a further Cochrane Review[116]115 comparing the more recently developed insulin analogues with synthetic "human" insulin, also showed that the research was "methodologically poor". As many as 81% of the studies were sponsored by the analogue insulin manufacturers themselves and the remaining studies had no sponsor stated. Insulin analogues are now taking over as first line treatment so no lessons have been learnt.

From this we have concluded that the quality of industry research has not improved and nor have the demands of the regulatory authorities become more vigilant in requiring better quality research.

From our experience, we have to raise the following points:

(a) the quality of studies carried out by the pharmaceutical companies wishing to market and promote a new drug;

(b) the lack of independent studies to inform decision making and the bias that may be introduced, especially publication bias that is likely to occur if the majority of the studies are carried out by industry who are unlikely to publish negative studies;

(c) the quality and efficiency of the marketing approval process whereby drugs are approved for use on the basis of largely poor quality research;

(d) the post marketing surveillance system which does not appear to require evidence from research carried out independently of the pharmaceutical industry; and

(e) in view of the lack of evidence of benefit of synthetic GM insulins, it is surprising that NICE has never evaluated insulin prescribing, assessed cost effectiveness and issued guidelines on insulin prescribing.

Our concerns are summarised by Edwin Gale, Professor of Diabetic Medicine in Bristol,[117]116 writing about the marketing of troglitazone, a Type 2 diabetes drug which had to be withdrawn for safety reasons six weeks after gaining marketing approval in the UK:

"Big pharmaceutical companies see clinical studies as a means of satisfying the regulators and promoting sales, not of providing information. Published reports are not designed to help clinicians persuade us to use the new agent effectively: they are selected and slanted in such a way as to persuade us to use the new agent. Hence the huge amount of junk literature of irrelevant and badly reported studies with misleadingly optimistic titles. No one will ever know how many people it (troglitazone) killed, perhaps between 200-1,000, yet the culture of secrecy protected the industry from full and timely disclosures of the mounting evidence of risk."

THE PROVISION OF DRUG INFORMATION AND PROMOTION

1. Advertising and promotion

While direct to consumer advertising of drugs (DTCA) is not allowed in the UK, we are concerned at the subtle ways in which industry circumvents this situation to reach the general public. We cite the following examples:

Û Using the press and celebrities to indirectly advertise. For example, the press covered TV chef Anthony Worall Thompson cooking for the staff of Novo Nordisk to launch their new analogue insulin Levermir.[118]117

Û Industry sponsorship of medical charities occurs frequently and while the agreement may be for sponsorship and not endorsement of their products, the perception of the charities' membership may well be different and the products seen as acceptable and even preferable by the charity associating itself with the company. Examples include an advertisement in Readers Digest May 2002 Diabetes UK supported by Novo Nordisk and the Sexual Dysfunction Association advertising in the March/April edition of consumer magazine, Balance has with Pfizer prominently on an advertisement.

Û The direct marketing to patients of insulin injection devices that can only be used with a particular company's insulin brand indirectly advertises and promotes the use of that particular insulin. (Complaint referred to and upheld by the ABPI complaints body)

2. Influencing and advertising to physicians

We are concerned at the close links between industry and the medical profession. After failing to obtain recognition of the adverse effects to synthetic GM insulin, some patients attempted legal action against the manufacturer Novo and attracted media attention as a result of sudden unexplained deaths. Novo employed a public relations company to defend the safety profile of genetically modified human insulin. They recommended a reactive strategy of a issues/crisis management programme that spanned three years and involved media training of company headquarters staff and UK medical spokespeople. The litigation collapsed and the PR company's description of the results was that Novo's reputation remaining intact among patients, health professionals and media, that sales continued to grow and the medical professionals accepted that human insulin has an excellent safety profile. While such action may have been in the best interests of the company and the promotion of their insulin, it has to be noted that the insulin could not be defended on the grounds of scientific evidence. It also demonstrates that there was unacceptable influence used to influence the medical profession and patients in favour their product.

To further quote Professor Edwin Gale[119]118 on the issue of troglitazone, but which could equally apply to synthetic GM insulins: "Not one physician stood up to say that the evidence base was inadequate and that no drug for diabetes is worth dying for . . . Our profession did nothing to protect the public. No one wants to remember troglitazone. It is treated as an unfortunate aberration of the system. It was not. It was a consequence of the system. Finding that out certainly changed my life."

3. Selective advertising

Industry stops advertising the drugs they no longer wish to promote in favour new more expensive drugs. While this is understandable from the company's perspective, it adversely affects patients being given an informed choice of treatment or alternatives if they experience adverse effects from the new product. For example animal insulins have not been advertised to physicians for many years and there is a perception amongst physicians and healthcare professionals that they are no longer available as a result of which they misinform patients.

4. Pharmaceutical company promotional materials

Promotional materials to medical and nursing staff affect prescribing habits. A survey[120]119 examining the influences on 227 diabetes specialist nurses showed that regardless of their lack of legal status to prescribe and patients' right to a an informed choice of treatment, 96% felt that they predominantly chose the insulin type. While this choice was primarily influenced by their personal experience of a given insulin type, the second influence was literature and pharmaceutical promotion of a particular insulin type and notably not scientific evidence of benefit.

5. Local pharmaceutical contracts

In some areas drug prescribing is influenced by prescriptive protocols and local pharmaceutical contracts for the exclusive use of a particular insulin brand. While this may reduce overall costs, it removes the right of choice from both patients and doctors.

6. The provision of drug information can be incomplete

We are concerned that in the UK patients and physicians are not provided with full information about risks and benefits and that this must in part be due to the actions of both industry and the regulatory authority in the UK.

Patients and physicians involved in diabetes care receive restricted information compared to the United States.

For example: Journals in the US make reference to the potential carcinogenic effects of insulin analogues in advertisements to both patients and professionals patients[121]120 but in the UK published journals have less information and do not include the potential for carcinogenic effects.[122]121, [123]122 The result is that treatment choices of both physicians and patients are not fully informed and there could be long-term health damage. The lack of this information cannot be explained as a matter of commercially sensitive information as all insulin analogues have this potential.

PROFESSIONAL AND PATIENT EDUCATION

We do not believe that pharmaceutical companies should be involved in patient or professional education as they have a vested interest in promoting their own products or company name. In our experience, industry's record to date in the provision of the required high quality evidence to inform treatment decisions leaves much to be desired as has been demonstrated by the issues raised throughout this document.

If industry wish to be magnanimous and support patient education programmes, then a system should be devised whereby they can donate to a central fund that then allocates funding to specific education programmes not necessarily in a specific company's particular section of the market.

115 Cochrane Collaboration Database, 2002. "Human" insulin versus animal insulin in people with diabetes mellitus. Back

116 Cochrane Database 2004. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Back

117 Professor Edwin Gale. Diabetes Digest; Vol 2 Number 4, 2003. Back

118 Crawley Observer. 30.6.04 Top chef cooks at town firm. Back

119 Professor Edwin Gale. Diabetes Digest; Vol 2 Number 4, 2003. Back

120 Practical Diabetes International; Sept 2003 Vol 20 No 7. Back

121 Diabetes Health, June 2004. Back

122 Practical Diabetes, July/August 2004. Back

123 Diabetic Medicine, July 2004. Back