Completion of Supervision Case – Breach of the Specialized Health Services Act and the Regulations Relating to Internal Control

On 30 March 2005 the Norwegian Board of Health Supervision received a communication expressing concern about a research project at Aker University Hospital Health Trust, called the “Hip Fracture Project” (“Investigation of risk factors for fracture of the hip, a prospective case control study”). Based on this communication, in April 2005 we initiated a supervision case in order to make an assessment of the project.

The study is part of the work for two PhD theses, and consists of several parts. In addition to the Hip Fracture Project, the study includes a clinical nutrition physiology study and a dental health study. This supervision case relates only to the orthopaedic part of the Hip Fracture Project. Professor Knut Strømsøe and Clinical Research Fellow Gurkipal Singh are responsible for the project.

Matters Relating to the Case According to the Documentation of the Case

Since the facts of the case are complicated, the Norwegian Board of Health Supervision has chosen to give an overview and a short description of the project first. Presentation of the case is based on information obtained from correspondence regarding the case, from a meeting held with the leadership of Aker University Hospital Health Trust on 28 June 2005, and from interviews at the hospital on 5 and 7 September 2005.

Description of the Project

In 2003, Aker University Hospital began a research project in which bone and muscle biopsies and blood tests were taken. Case histories and special diet histories were taken and physiotherapy assessments were made. The subjects were patients over 65 years of age who were admitted to hospital with hip fracture. Two types of hip fracture were assessed in the project: fracture of the upper femur and fracture of the trochanter. These assessments were made in order to identify risk factors and factors that can dispose patients to these types of fracture. All patients who were admitted with acute hip fracture were to be included, including patients with senile dementia. The control group was to be selected from randomized lists from the Central Office of the Population Register, matched for gender and age. It was not planned to take bone or muscle biopsies from the control group.

Later, the project was altered and extended several times, and other areas were included, among others dental health. Guidelines for information and consent were altered, and the descriptions of the procedures for all parts of the project were altered. In particular, the procedure for taking bone and muscle biopsies was altered.

Bone biopsies were taken using a hollow drill when a hole was made for inserting a pin as part of the treatment of the fracture. The muscle biopsies that were taken were 1 x 1 x 1 cm. At an earlier phase of the project (in 2003), muscle biopsies measuring 7 x 7 x 7 mm were taken. These were taken from a muscle (vastus lateralis) that is partially released from its attachment during the surgical procedure carried out in the treatment of fracture of the trochanter. This muscle is not normally incised as part of the treatment of fracture of the hip, but this had to be done in order to take the biopsy. It is stated that part of the study was to investigate whether there are differences between patients with fracture in the actual upper femur (cervical fracture) and patients with fracture of the trochanter (fracture between the femur and the upper femur). Below is a description of how these procedures were carried out, and an estimation of the increased time taken to carry out the surgery because of the project.

In the case of fracture of the upper femur (cervical fracture), the fracture is fixed with two LIH pins. There is no description in the orthopaedic department’s manual of the type of incision to be used in this kind of surgical procedure. According to the department’s senior consultant, the recommended incision has not been changed after the project started. From the interviews carried out on 7 September 2005, it was ascertained that before the project started some of the surgeons used a so-called percutaneous (peephole) technique with two small incisions of 1-2 cm, while all of them now use an open technique with a larger incision. Since it is necessary to carry out more dissection in order to take a muscle biopsy, most of the surgeons and nurses who were interviewed stated that the incisions are longer when a biopsy is taken.

At the interviews it was clarified that more dissection is necessary when muscle biopsies are taken. It was also ascertained that the department leadership recommended that a suture should be placed in the muscle on either side of the biopsy area, before the biopsy of 1 x 1 x 1 cm is taken. Most of the people who were interviewed reported that taking a biopsy causes more bleeding, and that this makes it necessary to use diathermy, or to use diathermy to a greater extent (for coagulation of blood vessels). Increased risk of bleeding was also stated as the reason why, early in the study period, the use of anticoagulants (Marevan) was added as an exclusion criterion. This is not stated in the project plan.

To take a bone biopsy, a hollow drill is first used to take out a cylinder of bone, instead of starting with the ordinary drill for an LIH pin. Then more drilling is carried out with an ordinary drill to the full length needed for the pin. It was reported in the interviews that there have been a few problems with the hollow drill. It has broken on some occasions, and sometimes it had heated up. The hospital reported that the method was tested with a “procedure trial” which included 100 patients. Tests from only ten of these patients have been partially analysed.

It was also reported that without a biopsy an experienced surgeon takes 20-25 minutes to carry out the actual operation (not including time for repositioning) with the LIH pin. An experienced surgeon uses 8-10 minutes to take the biopsy when he or she has gained experience with the procedure. A less experienced surgeon takes longer for both procedures. In addition, it takes longer to suture a longer incision. Thus, the total operation time is increased by up to 40 %.

In the case of fracture of the trochanter (fracture between the femur and the upper femur), so-called glide screws with a plate are used in the department. These are large screws that are placed through the upper femur, which can telescope in a casing in the plate. The method is often called CHS (Compression Hip Screw) or DHS (Dynamic Hip Screw).

Taking a biopsy does not influence the length of the incision, and has no major effect on dissection, in cases of fracture of the trochanter.

In the case of fracture of the trochanter, bone biopsies are taken “freehand” next to a leader pin for the compression screw (glide screw). The hole left after the biopsy is taken should fall within the hole for the glide screw after this has been drilled in place. The risk for this not happening is small, but cannot be excluded. If this does happen, the result can be a larger hole that weakens the bone.

Since, in the case of fracture of the trochanter, there is no need for much more dissection in order to take a muscle biopsy, the time taken to carry out this procedure is slightly shorter than with LIH pinning. Without taking a biopsy, an experienced surgeon takes about one hour to carry out a DHS operation. Thus the extra time taken for the operation is estimated to be about 10-15 per cent.

From the case documents it was ascertained that before biopsies were taken it was not clear which analyses should be carried out, and that no clear binding agreement had been made with a place where the analyses should be done. In the interviews with Singh and Strømsøe, it became clear that it is uncertain whether planned examinations of bone biopsies in Switzerland can be carried out according to the original plans, among other things, because this is very demanding of resources. Also, in the interviews, different answers were given about which analyses should be done at the AO Research Institute, Davos. It was also ascertained from correspondence by e-mail between the AO Research Institute and University Hospital, Northern Norway (UNN) and Aker University Hospital (AUS), that as late as the period from January 2004 until February 2005, discussions were still taking place about which analyses should be done and how they should be done.

he Number of Patients Included in the Project

In the course of dealing with the case, we have confirmed that from December 2003 until July 2004 100 patients have been included in the project. Blood tests were taken from these patients on admission, and bone and muscle biopsies were taken during the operation. Of the biological material from these 100 patients, only ten bone samples have been analysed. None of the patients had given prior consent for these tests. The experiments carried out on these patients are described afterwards as a “procedure trial”. Before the start of the project, this “procedure trial” is not described in any description of the project or in any other documentation we have received. The “procedure trial” is also not described in the description of the project sent to the Regional Ethics Committee (REK) and the Norwegian Data Inspectorate. It is therefore unclear whether this is part of the project or not. It is also unclear what a “procedure trial” is, since this is not a term used in research.

According to Singh’s statement of 7 June 2005, the aim of the “procedure trial” was to see whether the technique they wished to use functioned, and “whether it was at all possible to take bone biopsies in the desired way”. It is also stated that the aim was for the surgeons to be trained and to practice the new surgical technique, and to test the diamond drill (the cylinder drill mentioned previously), which they had made for the project. The surgeons were given instructions before the operation, but did not receive instruction during the operation unless they requested it.

However, in the first report from Singh (dated 3 May 2005) the first 100 patients are not mentioned. Singh only mentions the 40 patients who were included in the project after it was restarted on 24 January 2005. We only received information about the first 100 patients after direct questions from us during a telephone conversation with Bergesen (who was then medical staff director, now special adviser, health) on 10 May 2005.

From the start of the project in January 2005 and up to the time when the leadership at Aker University Hospital temporarily stopped the project in April 2005, 40 patients were included in the study. From the time the project restarted in July 2005 and up to the time when we gave an instruction to stop the project, a further 35 patients were included in the project. We did not receive a list of all the patients included in the project until after the instruction to stop the project was given.

Information and Consent

In the application to the Regional Ethics Committee, it is stated that the patients would be given information and that consent would be obtained. In the interviews, several of the people involved confirmed that consent was not obtained from these patients in advance, but only afterwards. The reasons given were that these patients are often in pain, they are under medication and they are not receptive for information because of their age and because of debility. It was further stated that it was not possible to obtain valid consent from these patients because of stress and lack of time in the acute situation. These reasons are given in Singh’s statement dated 3 May 2005. For most of the patients, consent was obtained at the 3 monthly check-up, while a few of the patients gave consent during their admission in the department. Even for patients who were competent to give consent, consent was not obtained in advance. It does not seem that each individual patient was assessed to see whether it was possible to obtain consent from them.

As far as we understand, consent for taking biopsies was obtained from the patients who were included in the project after July 2005.

he Biobank Act

The Norwegian Board of Health Supervision has received copies of the correspondence between the National Directorate for Health and Social Affairs (SHdir) and Singh.

On 15 October 2004, the application form for establishing a research biobank was sent to the National Directorate for Health and Social Affairs. With regard to consent and ethical issues the content of the application form is identical to that in the corresponding application form that was sent to the Regional Ethics Committee in the letter of 2 March 2004. In other words, it was not stated that patients with dementia without competence to give consent should be included. It is stated in the application that micro CT would be carried out at the AO Research Institute, Davos, Switzerland, and that histomorphometry would be carried out at the Orthopaedic Clinic, University Hospital, Malmø, Sweden. It is further stated that micro CT and histomorphometry is used for three-dimensional mapping of the structure of the bone in order to assess the type and extent of osteoporosis, if present. According to the application, these types of examination are not available in Norway.

In the letter of 3 November 2004, it is stated that the National Directorate for Health and Social Affairs had no objections to establishing a research biobank in accordance with the Biobank Act. Establishment of the biobank is on the condition that it fulfils “the necessary requirements related to approval, concession etc, in relation to other relevant legislation, including the Biotechnology Act, the Health Register Act and the Medicinal Products Act”. The Directorate further states that transference of the biological material abroad does not require approval, in accordance with the Biobank Act, Section 10, third paragraph and the Regulation of 26 February 2004 relating to transference of biobank material abroad. However, the Directorate specifically states that consent from the patient is required to transfer the material abroad, in accordance with the Biobank Act, Section 10, first paragraph, even though transference of the material does not require authorization.

It is apparent from the further correspondence that the Directorate did not know that material from patients with dementia who are not able to give valid consent would be included in the biobank. Therefore, the Directorate did not assess the Biobank Act, Section 12, last paragraph. This provision is interpreted and practised in such as way that a legally established biobank cannot contain human biological material from people over the age of consent who are not competent to give consent. Thus, according to the Directorate, the research biobank for the project at Aker University Hospital is not legally established.

In the decision of 5 September 2005, the Directorate instructed the Research Project to cease collecting biological material from patients who do not have competence to give consent, and to destroy material that had already been collected from this group of patients.

Other Authorizing Bodies

The project has received recommendations several times from the Regional Ethics Committee in Eastern Norway. The information in the application to the Regional Ethics Committee gives the impression that taking biopsies involves an insignificant extension of the operation. In the applications it has been crossed off that consent shall be obtained and that information shall be given to the patients. In addition, both a consent declaration  and a letter of information for patients about the project are enclosed. It is not stated in any of the applications to the Regional Ethics Committee that people with dementia who are not competent to give consent shall be included in the project.

As the person responsible for the project, Singh sent a total of six enquiries/applications to the Regional Ethics Committee. We refer in particular to the application to the Regional Ethics Committee dated 2 April 2003, which is the basis for the recommendations from REK. In the application form, under Point 4 about the description of the project, it is stated:

“Purpose: to identify risk factors for fracture of the hip. The aim is to identify patients at risk at an early stage, so that preventive measures can be initiated.

Hypothesis: The hypothesis is that there are differences in physiognomy (bodily composition) for patients who have fracture of the upper femur and those who have fracture of the trochanter.

Previously patients with fracture of the hip have been regarded as one group. It is necessary to divide the patients into two groups according to the type of fracture they have, since treatment, morbidity and mortality are very different for the two groups.

Method: The investigation will be carried out as a matched case-control study. The study will begin in the middle of May 2003. We will include, with consent, all patients who come in consecutively with acute fracture of the hip to Aker University Hospital Health Trust during one year. They will subsequently be called cases.

The controls will be selected from randomized lists from the Central Office of the Population Register, and they will be matched for age and gender. They will be from the urban districts that have Aker University Hospital as their local hospital for surgery.

Time period: May 2003-September 2004

(Both cases and controls) In accordance with the enclosed questionnaire, we will carry out an interview regarding case history, life-style variables and detailed nutrition history etc. Grip strength in the hands will be measured using an isometric dynamometer, and skin fold thickness will be measured using a skin fold meter.

All patients with fracture of the hip are operated on. During the operation we will take a piece of muscle 7 x 7 mm from the vastus lateralis muscle and a bone biopsy from bone fragments produced during drilling. The group is presently developing a protocol for how these biopsies will be analysed. Before analysis of these biopsies is begun, we will inform the Regional Ethics Committee about our plan and request authorization. Bone biopsies will be taken from the bone fragments that are produced when we drill in order to insert the pin. The size of the bone biopsy is so small that it will not inflict any additional trauma to the patient.

In addition, some blood tests will be taken.

According to the protocol, neurophysiological examinations will be carried out 2-4 weeks after the operation.

We also refer to the enclosed description of the project and the questionnaires.”

In the undated description of the project, which was enclosed with the application, biopsies are not mentioned. The Regional Ethics Committee gave recommendations for the study in the meeting held on 23 April 2003. It is mentioned in the actual application form that biopsies shall be taken from pieces of muscle and from bone fragments. In addition, it is stated that the project leader will inform the Regional Ethics Committee and will ask for authorization before analysis of the biopsies begins. On 28 May, Singh sent a new, updated application to the Regional Ethics Committee, giving information that a procedure for bone and muscle biopsies had then been developed. In the undated description of the project, it is stated under “with reference to the main aim” that:

“All patients with fracture of the hip are operated on according to earlier routines. The hole for the glide pin/pins is drilled with a hollow diamond drill that preserves the bone structure in the form of a bone cylinder with a diameter of 7 mm. This represents the bone biopsy. We will also take a 7 x 7 mm piece of muscle from the vastus lateralis muscle. Histomorphometry and structural micro CT will be performed on the bone biopsy. We have made an agreement with the AO Research Institute, Davos, Switzerland (Dr Marcus Egerman) to carry out these analyses. The following examinations will be carried out on the muscle biopsy: characterization of type of fibre, grade of atrophy, inflammation, necrosis etc. We have made an agreement with Prof. Sigurd Lindahl, University Hospital, Northern Norway, Tromsø to carry out these analyses”.

It is stated only in the application to the Norwegian Social Science Data Services (NSD) that patients with dementia who are not competent to give consent are included in the project. The reason for this according to the application is that the researchers wish to obtain scientific evidence that senile dementia can be considered to be a risk factor for the occurrence of fracture of the hip.

However, it is not clear from the completed application form to NSD that biopsies will be taken from the patients. This is only briefly stated in the written report to NSD dated 2 June 2003.

The ombudsman for personal protection (NSD) found that the interest for society was greater than the disadvantages for individuals, and recommended that information on patients who are not competent to give consent could be treated in accordance with the Personal Data Act, Section 8, Point d, and Section 9, Point h. On the basis of the recommendations from NSD, on 16 October 2003, the Norwegian Data Inspectorate granted a concession to analyse health data related to the project in accordance with the Health Register Act, Section 5 and the Personal Data Act, Sections 33 and 34.

Organization of the Research Project at Aker University Hospital

From the interview with the director, Hulda Gunlaugsdottir, we were informed that a research director was employed in the management from 1 September 2005. The research director is leader of a research committee for all the clinics.

Before 1 September 2005, research was carried out in all the clinics. In addition, there was a research centre. Thus, research could be carried out in the clinics, which the research centre did not know about. Each individual department leader was then responsible for the research projects.

The director did not know whether protocols or guidelines for the procedures to be followed when a research project is started were available. Later in the interview it was explained that there is no “check list” at the start of research projects.

Further, the director explained that she had ordered that the project should be discontinued when the supervision case was initiated. She demanded that the Ethics Committee should be informed, since the Committee had probably not assessed the project earlier. The Director knew about the questions that the Ethics Committee had asked about the project, but could not say what had been done after the Committee had given its statement. The project was restarted after 1 July 2005, but only with patients who were competent to give consent.

In the statement from the Clinical Ethics Committee dated 13 June 2005, it is stated:
“It is clear to the committee that the application to REK was incomplete on several points and that authorization for the project has therefore been granted on an unsound basis”.

It is further stated that the Committee advised the Director to restart the project, on the condition that all the patients were given adequate information and that consent was obtained.

Correspondence in the Supervision Case

Below is a list of all the correspondence regarding the supervision case, between Aker University Hospital and the Norwegian Board of Health Supervision.

On 30 March 2005 the Norwegian Board of Health Supervision received a communication expressing concern about the research project: the “Hip Fracture Project” Based on this communication, we initiated a supervision case in order to make an assessment of the project. In the letter of 27 April 2005, we asked for the following documents to be sent to us:
“Copies of protocols and other documents  sent to the Regional Committee for Medical Research Ethics, in connection with the research project being presented to the Committee for an ethical assessment. In addition, we request a copy of the Regional Ethics Committee’s assessment and recommendations. We also request copies of any internal guidelines, procedures, etc. that have been developed during implementation of the project. Finally, we request an account of how the project has been carried out in practice”.

In the letter of 4 May 2005 from Aker University Hospital, we received the following documents:

• completed application form to the Regional Committee for Medical Research Ethics, dated 28.05.2003
• invitation to participate in the Hip Study at Aker University Hospital Health Trust with consent declaration
• enquiry to the Hip Study at Aker University Hospital Health Trust with consent
• undated description of the project
• letter of 28.04.2003 from REK I regarding recommendations
• letter of 06.06.2003 from REK I regarding recommendations
• letter of 11.02.2004 from REK I regarding extension of the project and establishment of a biobank
• letter of 10.03.2004 from REK I regarding extension of the study and establishment of a biobank
• letter of 22.04.2004 from REK I regarding extension of the study
• concession from the Norwegian Data Inspectorate dated 16.10.2003
• letter of 03.11.2004 from the National Directorate for Health and Social Affairs regarding the research biobank and transference of biological material abroad
• description of internal procedure “bone biopsy in the case of fracture of the proximal femur”, February 2005
• description of internal procedure “muscle biopsy” and “bone biopsy”
• draft of 11.01.2005 “guidelines for inclusion of adults with lack of or reduced competence to give consent to participate in health research”, from the Internet, home-page of REK
• letter of 02.06.2003 to the Norwegian Social Science Data Services (NSD
• letter of 26.06.2003 from the Norwegian Social Science Data Services (NSD) with enclosed report to the Norwegian Data Inspectorate.

In the letter of 18 May 2005, the Norwegian Board of Health Supervision requested further documentation and a further account. Aker University Hospital replied to this request in the letter of 8 June 2005 with the following attachments:

• account of 07.06.2005 from the project leader Gurkipal Singh
• completed and submitted application form to REK dated 02.04.2003
• information letter: invitation to participate in the Hip Study at Aker University Hospital Health Trust, dated September 2003
• letter of 30.10.2003 to REK with additional information
• description of the project dated February 2003
• letter of 25.11.2004 from the Central Office of the Population Register, the Directorate for Taxes
• letter of 27.11.2004 from the Central Office of the Population Register, the Directorate for Taxes, with declaration of confidentiality signed by Gurkipal Singh
• letter of 29.01.2004 from REK regarding extension of the study
• letter of 02.03.2004 to REK regarding the application to establish a biobank, revised information to patients and consent declaration
• completed and submitted report form to the Norwegian Social Science Data Services (NSD), dated 24.03.2003
• completed and submitted application form for establishment of a research biobank, export of biological material, and altered, extended or new use of material collected earlier, dated 15.10.2004.

In the letter of 5 July 2005 from Aker University Hospital we received the following documents:

• letter of 04.07.2005 from department senior consultant Knut Strømsøe with summary and conclusions regarding length of stay and complications for patients included in the “procedure trial”, compared to patients operated before the study began
• print-out from the patient list for the Surgical Clinic, Orthopaedic Department
• copy of 41 consent declarations
• letter of 16.06.2005 from the Clinical Ethics Committee, Aker University Hospital

In the letter of 23 August 2005, the Norwegian Board of Health Supervision described the interviews carried out on 5 and 7 September 2005. In Gurkipal Singh’s letter of 8 September 2005, we received a copy of Singh’s e-mail correspondence with Grethe Halvorsen, the Norwegian Social Science Data Services. According to Singh, Halvorsen’s questions were answered in the letter to the Norwegian Social Science Data Services of 2 June 2003.

In the letter of 20 September 2005, the Norwegian Board of Health Supervision requested a more detailed description of the parameters for analysing the bone and muscle biopsies. We also requested copies of any correspondence between Aker University Hospital and the laboratories, information about which genetic analyses were desired for the project, which hospitals had cooperated with these analyses, and information about histological and image diagnostic examinations.

Aker University Hospital replied to this letter with the letter of 30 September 2005, with the following enclosures

• report of the examination of ten bone biopsies carried out at AO Research Institute, Davos, Switzerland,
• correspondence between the project leader and AO Research Institute, Davos, Switzerland of 09.12.2004,
• correspondence between the project leader and AO Research Institute, Davos, Switzerland of 19.01.2005,
• correspondence between the project leader and the Department of Pathology and Anatomy, University Hospital, Northern Norway, of 27.01.2005
• correspondence between the project leader and the Department of Pathology and Anatomy, University Hospital, Northern Norway, of 12.02.2005
• correspondence between the project leader and the Department of Pathology and Anatomy, University Hospital, Northern Norway, of 14.02.2005
• correspondence between the project leader and the Department of Pathology and Anatomy, University Hospital, Northern Norway, of 16.02.2005.

On 23 September 2005, the Norwegian Board of Health Supervision instructed Aker University Hospital to discontinue the part of the project that involved taking biopsies of the patients. The reason for the instruction was that, according to the assessment of the Norwegian Board of Health Supervision, there was no documentation that gave adequate grounds for taking bone and muscle biopsies as part of the project. According to the assessment of the Norwegian Board of Health Supervision, taking bone and muscle biopsies makes the operations more extensive, with subsequent increased risk of complications. We pointed out that the patients are elderly, and that carrying out more extensive operations is not justified in relation to the actual treatment, but in relation to the project. Because the justification for taking biopsies is inadequate, and because the procedure involves increased risk, the Norwegian Board of Health Supervision found that carrying out these tests did not meet the requirement of sound professional practice, in accordance with the Specialized Health Services Act, Section 2-2.
In the instruction to discontinue the project, we again requested a copy of the research protocol, which we had also asked for in the letter of 27 April 2005. We also requested a complete list of patients who had participated in the project.

In the letter of 3 October 2005 from Aker University Hospital, we received a list of the names of all the patients who had participated in the project. Also, we were informed that the research protocol had been enclosed as attachment 2: “Description of the project”, in their letter to us of 4 May 2005.

In the letter of 13 October 2005, Aker University Hospital appealed against the instruction to discontinue the project. In the appeal, Aker University Hospital referred to the fact that they had previously sent the research protocol, and that it was enclosed with the letter of appeal. We do not give an account of the appeal here, since an account of this was given and commented on in our letter of 2 December 2005 to the then Ministry of Labour and Social Affairs, the current Ministry of Labour and Social Inclusion.

We also received a copy of the letter of 13 December 2005 from Aker University Hospital to the then Ministry of Labour and Social Affairs.

In addition to the correspondence mentioned above, the documentation of the case includes a letter from the Regional Ethics Committee, dated 23 May 2005, in which all the documents that were sent to the Committee, and copies of the Committee’s letters to Singh, are enclosed. The Norwegian Board of Health Supervision has also received copies of the correspondence between Singh and the National Directorate for Health and Social Affairs, the Norwegian Data Inspectorate and the Norwegian Social Science Data Services (NSD).

On 30 September 2005, the Norwegian Board of Health Supervision applied to the Oslo Police District to consider prosecution of Knut Strømsøe, Gurkipal Singh and Aker University Hospital Health Trust. Aker University Hospital Health Trust were informed of this by telephone on 2 December 2005.

Statement dated 21 December 2005

Gurkipal Singh and Knut Strømsøe made a joint statement in the letter of 21 December 2005. In their statement, they maintain that the conclusions of the Norwegian Board of Health Supervision are based on an incorrect evaluation of the facts. They state that, in the assessment of the supervision case, it is important to take into account the content of the complaint made on 13 October 2005, in which several central issues are explained. In Appendix 1 to the statement, the project leader emphasized the scientific aspect of the project. In the Appendix, the scientific interest of identifying risk factors for fracture of the upper femur is described, based on differences in bone and muscle structures for elderly people with different types of fracture.

On page 8 of Appendix 1, it is stated that the bone biopsies:
“shall be analysed using micro CT in different ways to examine the bone structure in the area where the bone tissue was taken from. This analysis is carried out at AO Foundation’s Research Laboratory for Osteoporosis and Osteofixation Problems in Davos, Switzerland”.
With regard to the muscle biopsies, it is stated that they:
“shall be analysed using special analyses (histomorphometric and matrix analyses). It was planned to carry out the analyses in Gothenburg, but it was found to be more appropriate, both practically and economically, to have the muscle biopsies analysed in Tromsø (Professor Lindal). Some of the tests will be carried out at the Hormone Laboratory at Aker University Hospital”.

It is claimed in the statement that it is not correct that taking biopsies involved increased risk for the patients. According to the statement, this incorrect conclusion has been made because information that the Norwegian Board of Health Supervision collected regarding the supervision case is inadequate, and does not give a complete picture of the case. It is pointed out that during the period 2003-2004, the complications were no greater, and there were no different types of complication, than during the period 2000-2001, when no tissue samples were taken. The project leader cannot understand why the Norwegian Board of Health Supervision places more emphasis on subjective assessments from interviews about increased bleeding and length of time taken for the surgical procedure. A perusal of the 60 patient records that the Norwegian Board of Health Supervision was given access to, provides documentation that there was no clear difference in length of time taken for the surgical procedure before and during the project. Likewise, there is no evidence for the allegation of increased risk of bleeding and increased risk of complications. It is also not correct that it is necessary to make a larger incision when a biopsy is taken. It is pointed out that the method that is used is the same as the method used before the project began. The method “mini-invasive technique” (very short incision) is not used in the department. With LIH pinning of cervical fractures, the method developed by the manufacturer of the pins is used. In summary, it is claimed that taking biopsies has not led to increased risk, and that there is therefore no basis for an administrative reaction.

In the statement it is further claimed that the researchers were not familiar with the interpretation of the Biobank Act, Section 12, last paragraph, before July 2005. Before this, the project leader was not aware that there was no legislative authority to take biopsies of people who are not competent to give consent. However, it is not disputed that, objectively, a breach of the Biobank Act, Section 12 has taken place, since biopsies have been taken from patients who do not have competence to give consent. In relation to the assessment of whether a warning should be given, this must be assessed in the light of the fact that the breach of the Biobank Act took place in good faith. After July 2005, all the patients included in the project gave consent for the operation.

Further, it is claimed that:
“it is not correct that it is crossed off that consent shall be obtained, and that it is not stated that people who do not have the competence to give consent shall be included in the project. We forgot to cross of the point (point 7 in the application of 28 May 2003) relating to whether patients who do not have the competence to give consent would be included. This was a pure oversight, and is not the same as giving incorrect information......”.

It is pointed out that it is clear from point 8 in the application that patients who do not have the competence to give consent would be included. In point 8 it is stated that consent will be obtained from relatives if the patient himself or herself is not competent to give consent. The following quote is given from the statement:
“During the period from January 2005 until April 2005, we believed, based on the approval that had been granted, that our procedure regarding the inclusion of this group of patients was in accordance with the legislation. Our correspondence with the Norwegian Social Science Data Services and the Norwegian Data Inspectorate had not given any signals to the contrary”.

If the Norwegian Board of Health Supervision maintains its allegation that “the value of the project is not in line with the alleged risks to the patients”, we request that an impartial professional commission is established to assess this.

In addition, Strømsøe made an additional statement in the letter of 23 December 2005, in which he states:
“As leader of the department, I have overall responsibility for the patients treated in the department. It is my responsibility to check the quality of all routines and methods of treatment in the department.
As supervisor for Research Fellow Gurkipal Singh, I have overall responsibility for his research project. G. Singh is a full-time university employee, and I, as part-time professor at the University, have responsibility for his research work.
Both these functions mean that I have main responsibility for ensuring that legislative requirements are met”.

The Norwegian Board of Health Supervision does not regard it as necessary to refer to the other documents in the case. These were enclosed with the orientation about the administrative reaction, dated 2 December 2005.

he Assessment of the Norwegian Board of Health Supervision

On the basis of the above comments, and other information about the case, the Norwegian Board of health has assessed whether Aker University Hospital Health Trust (hereafter called the Health Trust) has acted in breach of the requirements laid down in health legislation.

This has been assessed according to the provision in the Specialized Health Services Act, Section 2-2, which states:

Health services that are offered or provided in accordance with this Act shall be in accordance with sound professional standards.

This has also been assessed in relation to the requirement for internal control, founded on the Regulation Relating to Internal Control in Health and Social Services (the Internal Control Regulation), Section 4, in accordance with the Health Personnel Act, Section 16 and the Specialized Health Services Act, Section 2-1a.

The Internal Control Regulation, Section 4, states:

Internal control shall be adapted to the size of the enterprise, its characteristics, activities and level of risk, and be as comprehensive as is necessary to meet the requirements laid down in or in accordance with health and social legislation.

Internal control involves that the person or persons who are responsible for the enterprise shall:

a) describe the main tasks and aims of the enterprise, including the aims of quality improvement work and how the enterprise is organized. The way in which responsibility, tasks and authority are allocated shall be clear.

b) ensure that relevant acts and regulations that apply to the enterprise are available.

 c) ensure that employees have adequate knowledge and skills within the relevant professional areas, and about the enterprise’s internal control.

d) ensure that employees participate so that collective knowledge and experience are utilized.

e) use the experiences of patients/clients and relatives to improve the quality of the enterprise.

f) obtain an overview of areas of the enterprise where there is a danger of deficiencies occurring or of statutory requirements not being met.

g) develop, implement, control, evaluate and improve necessary procedures, instructions, routines or other measures for identifying, correcting and preventing breaches of health and social legislation.

h) carry out systematic surveillance and review of internal control, to ensure that it functions as intended and contributes to continual improvement in the enterprise.  

We refer also to the Supervision of Health Services Act, Section 3, which states:

Everyone who provides a health service shall establish an internal control system for the activity and ensure that the activity and the services are planned, provided and maintained in accordance with requirements laid down in or pursuant to laws and regulations.

The Norwegian Board of Health Supervision in the county shall ensure that everyone who provides health services has established an internal control system and carries out control with their own activity in such a way that failure in the health services may be prevented.

The first theme for assessment is whether there has been a breach of the Specialized Health Services Act, Section 2-2. The Norwegian Board of Health Supervision, in a decision of today, has given those who are responsible for the project, Gurkipal Singh and Knut Strømsøe, a warning, in accordance with the Health Personnel Act, Section 56 for several breaches of the requirement to act in accordance with sound professional standards in the Health Personnel Act, Section 4. In addition, the researchers have acted in breach of the Biobank Act, Section 12, last paragraph. They have also given misleading and incomplete information to the authorization authorities. As described in these decisions, which the Health Trust has received a copy of, and in our instruction to stop the project dated 23 September 2003, the Norwegian Board of Health Supervision finds that the research project is in breach of the requirement to act in accordance with sound professional standards. The grounds for this is that an experiment has been initiated on patients without the project having been adequately planned so that it was defensible to include patients in the project, and without consent being obtained from the patients. Further, we find that, with reference to the fact that the grounds for taking biopsies were inadequate and that the surgical procedure involved increased risk, that it was not in accordance with sound professional standards to take the actual tests, pursuant to the Health Personnel Act, Section 4.

It is not stated whether the Health Trust/hospital management was adequately informed about the project from the start, but the Norwegian Board of Health Supervision points out that the Health Trust has responsibility for ensuring that the treatment offered to patients is in accordance with sound professional standards, pursuant to the Specialized Health Services Act, Section 2-2. When the Health Trust/hospital management was informed about the supervision case in April 2005, the project was stopped. However, the management chose to restart the project in July 2005. The Norwegian Board of Health Supervision cannot see that the hospital management has made an adequate, thorough assessment of the project in terms of sound professional standards, but that they have based their assessment on the information they received from the project leader.

After the project leader was informed about the interpretation of the Biobank Act in July 2005, patients without competence to give consent were not included in the project. According to the assessment of the Norwegian Board of Health Supervision, it is not sufficient to justify starting the project again on the basis of the fact that consent would henceforth be obtained. It follows from the Biobank Act, the Helsinki Declaration and the general requirement of sound professional standards, that for consent to be valid it must be informed. The Norwegian Board of Health Supervision bases its assessment of the validity of consent on the following: in order for consent to be valid, it must be based on information about aims, method, risk, discomfort, consequences and other relevant factors. The consent declarations we were shown (4-5 different consent declarations) do not meet these requirements with regard to information about taking biopsies. The written information to the patients that we have been shown, is not adequate information about the study, and particularly not about the taking of biopsies. Only brief information is given that the patient will not notice anything when the biopsy is taken. The patient is not informed about exactly which tests shall be performed, nor about the consequences this can have in terms of side-effects and complications. Consent given on the basis of this information can therefore not be regarded as informed consent.

After an overall assessment, with reference to the inadequate grounds for taking biopsies and for what the biopsies shall be used for, the Norwegian Board of Health Supervision finds that it is not possible to obtain valid, informed consent with the protocol/description of the project and the consent declarations in their present form.

Based on the above assessment, the Norwegian Board of Health Supervision finds that the research project is in breach of the requirement of sound professional standards, both in the Health Personnel Act, Section 4, and in the Specialized Health Services Act, Section 2-2. The hospital is responsible for ensuring that services that are offered are in accordance with sound professional standards, and they are thus also responsible for the project.

The next matter to assess is whether the hospital has fulfilled its duty in relation to organization and follow-up of the research project that it is responsible for.

The duty for internal control is the duty to ensure that the enterprise is run in accordance with requirements laid down in or pursuant to health legislation. It is apparent from the documents in the case that responsibility for the project was left up to the individual clinics. The Health Trust does not appear to have had routines or other systematic measures to ensure that research is carried out in accordance with health legislation.

According to the assessment of the Norwegian Board of Health Supervision regarding organization of research at the hospital, systematic measures for ensuring that statutory requirements are met, are lacking. The breaches of the law that the Norwegian Board of Health Supervision has pointed out in the decisions to give warnings to the researchers, clearly show the possible consequences. On this background, the Norwegian Board of Health Supervision finds that a breach of the Internal Control Regulations, Section 4 has taken place.

Further, the Norwegian Board of Health has assessed the responsibility of the hospital in relation to the establishment of a biobank.

In the Biobank Act, Section 17, it is stated:
The Norwegian Board of Health Supervision shall in accordance with the Supervision of Health Services Act carry out supervision of whether statutory provisions are met.

In the Biobank Act, Section 7, a more detailed description of who is responsible for the biobank is given, as follows:
Each biobank shall have a responsible person with higher education in medicine or biology. If the biobank contains information that can be linked to individual persons, it will also have a person responsible for treatment in accordance with the Personal Health Data Filing System Act or the Personal Information Act. The person responsible for treatment shall appoint the person responsible for the biobank. The Ministry can decide that a biobank shall have a committee in addition to a responsible person.

The responsible person and the committee shall ensure that the biobank is established and administered in accordance with this Act and other acts.

The Ministry can in regulations make specific provisions regarding which biobanks shall have a committee, and the committee's tasks and composition etc.

Provisions relating to consent for research biobanks are regulated in the Biobank Act, Section 12, as follows:

If no specific statutory authority or other valid legislative authority exists, collection, storage and processing of human biological material for research purposes requires voluntary and informed consent from the donor. This also applies to storage and use of information associated with the biological material.

Documentation must be available that consent has been obtained. Consent must be based on information about aims, methods, risks, discomfort, consequences and other factors that are relevant for the validity of the consent. The requirements for information and specification must be decided based on an assessment of the risk factors, the sensitivity of the material, the vulnerability of the study participants and other similar factors.

Material in biobanks cannot be loaned or distributed to others or sent abroad, unless consent has been given for this.

For removal of human biological material from a deceased person the provisions in the Transplantation Act relating to presumed consent for post-mortem examination apply.

For persons who do not have the competence to give consent in accordance with the Patients' Rights Act, Section 4-3, the Patients' Rights Act, Sections 4-4, 4-5 and 4-7 relating to consent to health care on behalf of others, apply for the collection, storage and processing of biobank material for research.

For persons over the age of consent who do not have the competence to give consent in accordance with the Patients' Rights Act, Section 1-3, the next-of-kin can give consent on the person's behalf for the collection, storage and processing of biobank material for research .

It is clear that a breach of the Biobank Act, Section 12 last paragraph has taken place, since biological material was taken from patients who did not have competence to give consent. This provision is interpreted and practiced in such a way that a legally established biobank cannot contain human biological material from persons over the age of consent who do not have competence to give consent. The research biobank for the project has therefore not been legally established.

According to the application to establish a research database, and the letter from the National Directorate for Health and Social Affairs of 3 November 2004, Gurkipal Singh is responsible for the research biobank. In accordance with the Supervision of Health Services Act, Section 3, and the Regulations Relating to Internal Control, Section 4, the hospital has overall responsibility for ensuring that the organization meets the statutory requirements in the field of health. According to the assessment of the Norwegian Board of Health Supervision, this means that the hospital also has overall responsibility for ensuring that the regulations in the Biobank Act are complied with. In accordance with the Regulations Relating to Internal Control, the hospital should have had routines to ensure that the biobank was legally established.

Summary

The Norwegian Board of Health Supervision finds that Aker University Hospital Health Trust, as responsible Health Trust has not ensured that the research project: “Investigation of risk factors for fracture of the hip, a prospective case-control study” has followed the requirements laid down in the Specialized Health Services Act, Section 2-2, the Regulations Relating to Internal Control, Section 4, and the Biobank Act, Section 12.

Conclusion

The Norwegian Board of Health Supervision finds that there are grounds to give Aker University Hospital Health Trust criticism for breach of the Specialized Health Services Act, Section 2-2, the Regulations Relating to Internal Control, Section 4 and the Biobank Act, Section 12.

We expect Aker University Hospital Health Trust henceforth to organize its research projects in accordance with current legislation.

Yours sincerely,

Lars E. Hanssen

 
Copy:
The Norwegian Board of Health Supervision in Oslo and Akershus
The Regional Committee for Medical Research Ethics
Eastern Norway Regional Health Authority
Gurkipal Singh
Knut Strømsøe
The Ministry of Labour and Social Inclusion
Oslo Police District, Kjetil Moen
National Directorate for Health and Social Affairs
Norwegian Data Inspectorate
Regional Ethics Committee (Eastern Norway)

Executive Officer: Hanne Knudsen, tel.: 21 52 99 26
Executive Officer, Health Care Specialists: Senior Advisor Geir Stangeland, Director of Department Jørgen Holmboe and Specialist in Orthopaedics Norvald Langeland