Consent to using human tissue

Human tissue is vital for teaching, laboratory quality control, and research—work done for the good of all. Consent is required to legitimise such use. But how should consent be sought?

Dramatic recent publicity about inadequate consent procedures for autopsy has engendered new regulations that have been applied to all human samples—surgical resections, biopsies, blood, urine, even sputum.¹ As an example of the consequences an international study of a rare form of kidney disease has recently been abandoned because the requirement for central review of microscope slides—which contain micrograms of human tissue—was deemed to require explicit consent from patients in the United States and the United Kingdom. The situation in other European countries is varied, but none has regulations as restrictive as the United Kingdom.

Is the United Kingdom leading the way or overreacting? Autopsy specimens have great emotional importance, but patients rarely regard tissue that has been removed for therapeutic purposes in the same light.² The experience of the Peterborough tissue bank emphasises this. Of 3140 patients 98.8% (3102) gave consent for surgically resected tissue to be used in research by commercial organisations, which is usually thought to be more troubling to patients than other sorts of research.³ The rate of consent to use postmortem tissue for any purpose was much lower.⁴

In the United Kingdom pathology laboratories in the NHS examine and subsequently store over 3 million tissue specimens each year. Specimens from living patients vastly outnumber autopsy specimens, and the absence of autolysis makes tissue from living people technically preferable for most purposes. The size of this resource makes even the largest research tissue banks seem pitifully small, but its use is now severely limited by the new regulations.¹

Ethicists devising these regulations took consent to participation in clinical trials as their model. In such trials the patient is physically present, and participation carries an element of risk. Those drafting regulations initially assumed that researchers should “simply” ask the patients for consent. But the analogy does not hold. As we have recently shown, to obtain consent for archival tissue samples is far from simple.⁵

The new regulations apply to all use of human tissue, even the most innocuous. When Marshall and Warren tentatively suspected that micro-organisms might cause gastritis, they first reviewed microscope sections from 100 gastric biopsies.⁶ That's research using human tissue. So under current United Kingdom regulations they would now have to complete a 45 page ethical review form (www.corec.org.uk). The ethics committee would probably require informed consent from all 100 patients—who had presumably all gone home and might not have been contactable. It is reasonable to infer that in the United Kingdom today, Helicobacter pylori could not be discovered. The potential consequences for patients are alarming.

To require explicit consent from every patient takes due account of the autonomy of the few who object. But it also has ethically undesirable consequences.

• It disrespects the autonomous wishes of the many who want to help medical research³ (at no cost to themselves) but who cannot be contacted.

• If research is blocked those who want to help research and can be contacted also have their wishes frustrated.

• Those would benefit from the results are damaged.

• Reviving memories about samples taken long ago can cause distress.

Is the balance right? To resolve this problem, could we ascertain the wishes of all patients whenever samples are taken, record the wishes, and thereafter act accordingly? This would provide only “generic” consent. It could permit uses that are not controversial and pose no risk to the interests of the tissue donor; but this encompasses most tissue based research. Data from Peterborough also raise questions about widespread assumptions concerning what is controversial. Of the 3140 patients approached, only two (0.06%) refused because of the intended commercial use, despite its supposedly controversial status.³

Unfortunately, to record everyone's wishes has major implications for resources, with 3 million tissue specimens per year in the NHS, a figure that ignores blood samples. Proponents of a short clause on the surgical consent form also ignore blood samples, and a recent audit in Leeds reported serious problems in relation to patients' understanding and clinicians' compliance.⁷

So is implied consent—provide an information sheet and invite objections—a possibility for the use of tissue from living patients for research? Is it reasonable for the majority to ask the small minority who object to make their wishes known? In a recent debate in the BMJ both participants assumed that implied consent would suffice.⁸ Implied consent was in essence the Nuffield Council on Bioethics' recommendation in 1995,⁹ but it has since been rejected by the Medical Research Council,¹⁰ despite evidence that patients thought the Nuffield recommendations were appropriate.¹¹ The Department of Health for England has so far taken a similar line to the MRC.¹ Implied consent is accepted by the Department of Health for using “surplus” tissues in quality control,¹² but explicit consent is now the norm for research.¹ The latest proposals now demand explicit consent for teaching, which will pose problems—especially in histopathology.¹³ Using tissue without consent will be a criminal offence.

Acting on individual patients' wishes has implications for resources. An efficient system to record and retrieve those wishes is required, whether explicit or implied consent is used. This is already needed even to check for objectives to use of human tissue samples in teaching and quality control. Yet at a recent meeting of academic pathologists in Bristol, not one participant could claim that his or her local hospital had implemented such a system. So research is being inhibited; but for teaching, quality control, and audit, consent issues are still being ignored.

If we are serious about empowering patients to control the use of their tissue samples, resources must be allocated irrespective of whether implied or explicit consent is regarded as appropriate. Without such resources our laboratories are forced into paralysis or continuing paternalism. At present we have both.