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Macchiarini Fallet Report Summary

• The report investigates the activities of synthetic trachea transplantations at Karolinska University Hospital.
• It focuses on shortcomings exposed during the investigation and areas where improvements may be needed.

Key Entities Involved

• Paolo Macchiarini: Professor at Karolinska Institutet and senior physician at Karolinska University Hospital, terminated in November 2013.
• Kjell Asplund: Professor Emeritus of Medicine at Umeå University, appointed as an external investigator.
• Stockholm County Council: Decided to give a mandate for the investigation and provided administrative support.
• Karolinska Institutet (KI): Involved in the employment and activities of Macchiarini, with focus on academic activities.

Timeline of Events

• End of 2010: Paolo Macchiarini employed.
• 2011: First transplant of a synthetic trachea. Reports emerged of cooperation difficulties.
• 2011-2013: Macchiarini performs synthetic trachea transplants on two more patients.
• January 2013: First transplant patient dies after severe complications.
• November 2013: Macchiarini's employment terminated.
• August 2014: Physicians report Macchiarini for research misconduct.
• April 2015: Swedish Medical Products Agency files police report against Karolinska University Hospital.
• June 2015: The Health and Social Care Inspectorate (IVO) files a police report against the hospital.
• January 2016: Growing criticism culminates in TV series, Vice-Chancellor of KI and his colleagues resign.
• March 2016: Personnel Disciplinary Board dismisses Macchiarini.
• March 1, 2016: Pernilla Östlund hired as a research assistant.
• February 12, 2016: Hospital director Melvin Samsom decided to give a mandate for an external investigation.
• August 31, 2016: Inquiry report completed.

Glossary of Terms

• Bioengineering: Applying biological techniques to modify organisms, used for modifying organ characteristics.
• Biocompatible: Compatible with living tissue, not toxic, harmful, or immunologically reactive.
• Bronk: Airway branching from the trachea into the lungs.
• ECMO: Oxygenation outside the body to rest/heal lungs/heart, an "artificial lung".
• Epitel: Outermost cell layer of skin and mucous membranes.
• Fistel: Abnormal channel within the body.
• In vitro-studier: Studies outside the living body.
• In vivo-studier: Studies within the living body.
• Nekrotrakea: Trachea from a deceased person.
• Regenerative kirurgi: Part of regenerative medicine involving surgical techniques.
• Regenerativ medicin: Medicine focused on replacing damaged tissue with new tissue.
• Stent: Tubular prosthesis used to keep passages open.
• Trakea: The trachea, or windpipe
• Translationell forskning: Research aimed at transitioning scientific discoveries to new prevention, diagnosis, and treatment methods.

Inadequacies Identified

• Critical opinions from previous employers not taken seriously during recruitment.
• Lack of references taken by the hospital on Macchiarini's clinical qualifications during recruitment.
• Placement of Macchiarini at the ENT clinic rather than thoracic clinic contributed to unclear responsibility.
• Patients' conditions were not immediately life-threatening before operations.
• Weaknesses in obtaining informed consent and continuity of patient-treating physician contact.
• Inadequacies in the synthetic material used for transplants.
• Deviation from acceptable pharmaceutical treatment.
• Scientific foundation inadequate prior to transplants.
• Transplants should have been subjected to ethical review.
• Laws and regulations were not followed, Ethical Review Act regulations disregarded.
• Multiple problems concerning patient safety.
• Lack of critical questions and ignorance regarding regulations.
• Complex relationship between the hospital and KI.
• Potential misconduct may have affected patient care by positively describing the initial effects.
• Lack of clarity on who was responsible for keeping the department safe.
• Heads of ENT and thoracic surgery departments did not adequately act, warnings not taken seriously.

Patient Outcomes

• First Transplant Patient (36-year-old man): Died 30 months after the procedure due to severe complications; autopsy revealed transplanted trachea had come loose, chronic chest infection, and a clot in the right pulmonary artery.
• Second Transplant Patient (30-year-old man): Died suddenly in March 2012, cause unknown; speculation of death being related to directly transplant or underlying cancer
• Third Transplant Patient (22-year-old woman): Suffered severe complications requiring continuous hospital care since 2012, and underwent multiple organ transplant in May 2016; still in the hospital as of August 2016 but partially ambulatory.

Scientific Foundation

• Inadequate scientific support, conflicted with scientific and proven experience; too early to conduct a study.
• Two main research lines on trachea transplantation: (a) trachea/structures from deceased donors and (b) trachea made of synthetic material.
• Mixed results in animal studies, with limited research using the specific techniques applied in clinical transplants.

Laws and Regulations

• Transplants constituted clinical research
• Ethical Review Act regulations not applied, required research ethics review not conducted, which was crucial
• Permits for the combination of synthetic trachea, bone marrow cell preparation, and non-approved pharmaceuticals were not obtained. Contacts with permit-issuing bodies handled informally over the phone allowing for divergent interpretations. Regulations for healthcare were partly applicable, but the management system, information/consent regulations, and second opinions inadequately handled.

Patient Safety

• Signs of inadequacies in patient safety work led to risks concerning patient safety and diminished feelings have been noticed.

Factors Contributing to the Course

• There was group thinking.
• Bandwagon effects
• Lack of knowledge and respect for rules.
• A competitive environment with informal leaders
• The culture of silence in hospital.
• Variability in the knowledge of and respect for the rules.
• Ambitions to work against a repressive culture have not achieved a full breakthrough.

Relationship between hospital and KI

• Macchiarini = greater at KI than hospital
• Hospital not independent enough from KI.

Consequences for clinical research and employees

• Harmed employees at the hospital damage was caused by the Macchiarini case Targeted work-environment efforts are required in the work environment area.
• Damaged clinical research and needs to improve the clinical research in general.

Hospital's Actions

• Task force addressing issues between healthcare and clinical research
• Whistle-blower function established Chief medical officer gathering information on the patients Macchiarini operated on at the hospital Effort to strengthen patient safety at thoracic clinic

Necessary steps for hospital managment

• Recruitment process must be quality assured, independence from KI must be demonstrated.
• Extensive training in rules and guidelines.
• Patient safety must central systematic review required & follow-up.
• Department of thoracic surgery requires improvement.
• Quality assurance for decision-making.
• Transparency re increased one point expertise must be increased.
• Several recommendations reducing space for independence leading to potential patient safety concerns
• Work needs to continue to counter repressive elements.
• the conflits and work environment problems the case has created.

Investigation Details

• Director of Karolinska University Hospital commissioned the investigation
• Assignment was to answer questions surrounding Macchiarini and the transplants.
• Questions that have asked: Under what circumstances and conditions were the steps taken?
• Was the choice of measures correct based on available knowledge and guidelines?
• What ethical assessments -Guidelines? Decisions on operations and care? Steps due to the activities? Relevancy to the assessment of activities?
• Kjell Asplund, lead medicine Task to assigned to
• working group included: medical officials
• Secretary was. Pernilla Ölstlund
• Issues from mentioned in our report if they were relevant
• Several other investigations in for the the topic
• Regular contact with the people
• Based on Skl handle book event analysis
• Identified who will the interview more than 60 interviews of Macchiarini. - and his activities at the hospital.
• Four external in total
• Review chapter and sections.
• View to be made by Paolo
• Have hired to reviewers: Professor - Petersson as a head Research at Skå University and - Professor Jack-Lysholm, head the centre Norr, Umea Two external experts: chief as a Jan Nyman Chief of Oncology

Trachea Transplants

Medical History of patients:

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Medical Products and Drugs

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